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Early-onset Parkinson disease v3.0 PPP2R2B_SCA12_CAG STR PPP2R2B_SCA12_CAG: gene migrated from ENSG00000156475 to ENSG00000156475 (gene set migration)
Early-onset Parkinson disease v3.0 TBP Gene migrated from ENSG00000112592 to ENSG00000112592 (gene set migration)
Early-onset Parkinson disease v3.0 TAF1 Gene migrated from ENSG00000147133 to ENSG00000147133 (gene set migration)
Early-onset Parkinson disease v3.0 PPP2R2B Gene migrated from ENSG00000156475 to ENSG00000156475 (gene set migration)
Early-onset Parkinson disease v3.0 HTT Gene migrated from ENSG00000197386 to ENSG00000197386 (gene set migration)
Early-onset Parkinson disease v3.0 FMR1 Gene migrated from ENSG00000102081 to ENSG00000102081 (gene set migration)
Early-onset Parkinson disease v3.0 C9orf72 Gene migrated from ENSG00000147894 to ENSG00000147894 (gene set migration)
Early-onset Parkinson disease v3.0 ATXN8 Gene migrated from HGNC:32925 to ENSG00000288330 (gene set migration)
Early-onset Parkinson disease v3.0 ATXN2 Gene migrated from ENSG00000204842 to ENSG00000204842 (gene set migration)
Early-onset Parkinson disease v3.0 ATXN3 Gene migrated from ENSG00000066427 to ENSG00000066427 (gene set migration)
Early-onset Parkinson disease v3.0 JPH3 Gene migrated from ENSG00000154118 to ENSG00000154118 (gene set migration)
Early-onset Parkinson disease v3.0 ANG Gene migrated from ENSG00000214274 to ENSG00000214274 (gene set migration)
Early-onset Parkinson disease v3.0 FUS Gene migrated from ENSG00000089280 to ENSG00000089280 (gene set migration)
Early-onset Parkinson disease v3.0 HEXA Gene migrated from ENSG00000213614 to ENSG00000213614 (gene set migration)
Early-onset Parkinson disease v3.0 ATXN10 Gene migrated from ENSG00000130638 to ENSG00000130638 (gene set migration)
Early-onset Parkinson disease v3.0 TMEM230 Gene migrated from ENSG00000089063 to ENSG00000089063 (gene set migration)
Early-onset Parkinson disease v3.0 DNAJC13 Gene migrated from ENSG00000138246 to ENSG00000138246 (gene set migration)
Early-onset Parkinson disease v3.0 DCAF17 Gene migrated from ENSG00000115827 to ENSG00000115827 (gene set migration)
Early-onset Parkinson disease v3.0 RIC3 Gene migrated from ENSG00000166405 to ENSG00000166405 (gene set migration)
Early-onset Parkinson disease v3.0 OPA3 Gene migrated from ENSG00000125741 to ENSG00000125741 (gene set migration)
Early-onset Parkinson disease v3.0 WASL Gene migrated from ENSG00000106299 to ENSG00000106299 (gene set migration)
Early-onset Parkinson disease v3.0 GIGYF2 Gene migrated from ENSG00000204120 to ENSG00000204120 (gene set migration)
Early-onset Parkinson disease v3.0 ALPL Gene migrated from ENSG00000162551 to ENSG00000162551 (gene set migration)
Early-onset Parkinson disease v3.0 PODXL Gene migrated from ENSG00000128567 to ENSG00000128567 (gene set migration)
Early-onset Parkinson disease v3.0 TUBB4A Gene migrated from ENSG00000104833 to ENSG00000104833 (gene set migration)
Early-onset Parkinson disease v3.0 PSEN2 Gene migrated from ENSG00000143801 to ENSG00000143801 (gene set migration)
Early-onset Parkinson disease v3.0 KCNJ15 Gene migrated from ENSG00000157551 to ENSG00000157551 (gene set migration)
Early-onset Parkinson disease v3.0 MT-ND6 Gene migrated from ENSG00000198695 to ENSG00000198695 (gene set migration)
Early-onset Parkinson disease v3.0 COASY Gene migrated from ENSG00000068120 to ENSG00000068120 (gene set migration)
Early-onset Parkinson disease v3.0 AFG3L2 Gene migrated from ENSG00000141385 to ENSG00000141385 (gene set migration)
Early-onset Parkinson disease v3.0 EPM2A Gene migrated from ENSG00000112425 to ENSG00000112425 (gene set migration)
Early-onset Parkinson disease v3.0 TENM4 Gene migrated from ENSG00000149256 to ENSG00000149256 (gene set migration)
Early-onset Parkinson disease v3.0 NHLRC1 Gene migrated from ENSG00000187566 to ENSG00000187566 (gene set migration)
Early-onset Parkinson disease v3.0 DHDDS Gene migrated from ENSG00000117682 to ENSG00000117682 (gene set migration)
Early-onset Parkinson disease v3.0 PTPA Gene migrated from ENSG00000119383 to ENSG00000119383 (gene set migration)
Early-onset Parkinson disease v3.0 APP Gene migrated from ENSG00000142192 to ENSG00000142192 (gene set migration)
Early-onset Parkinson disease v3.0 DDC Gene migrated from ENSG00000132437 to ENSG00000132437 (gene set migration)
Early-onset Parkinson disease v3.0 KIF5A Gene migrated from ENSG00000155980 to ENSG00000155980 (gene set migration)
Early-onset Parkinson disease v3.0 PNPLA6 Gene migrated from ENSG00000032444 to ENSG00000032444 (gene set migration)
Early-onset Parkinson disease v3.0 UQCRC1 Gene migrated from ENSG00000010256 to ENSG00000010256 (gene set migration)
Early-onset Parkinson disease v3.0 PDGFRB Gene migrated from ENSG00000113721 to ENSG00000113721 (gene set migration)
Early-onset Parkinson disease v3.0 PDGFB Gene migrated from ENSG00000100311 to ENSG00000100311 (gene set migration)
Early-onset Parkinson disease v3.0 MECP2 Gene migrated from ENSG00000169057 to ENSG00000169057 (gene set migration)
Early-onset Parkinson disease v3.0 GCH1 Gene migrated from ENSG00000131979 to ENSG00000131979 (gene set migration)
Early-onset Parkinson disease v3.0 PINK1 Gene migrated from ENSG00000158828 to ENSG00000158828 (gene set migration)
Early-onset Parkinson disease v3.0 SLC20A2 Gene migrated from ENSG00000168575 to ENSG00000168575 (gene set migration)
Early-onset Parkinson disease v3.0 SNCA Gene migrated from ENSG00000145335 to ENSG00000145335 (gene set migration)
Early-onset Parkinson disease v3.0 GLB1 Gene migrated from ENSG00000170266 to ENSG00000170266 (gene set migration)
Early-onset Parkinson disease v3.0 CLN3 Gene migrated from ENSG00000188603 to ENSG00000188603 (gene set migration)
Early-onset Parkinson disease v3.0 SLC6A3 Gene migrated from ENSG00000142319 to ENSG00000142319 (gene set migration)
Early-onset Parkinson disease v3.0 NPC2 Gene migrated from ENSG00000119655 to ENSG00000119655 (gene set migration)
Early-onset Parkinson disease v3.0 NPC1 Gene migrated from ENSG00000141458 to ENSG00000141458 (gene set migration)
Early-onset Parkinson disease v3.0 NUS1 Gene migrated from ENSG00000153989 to ENSG00000153989 (gene set migration)
Early-onset Parkinson disease v3.0 PGK1 Gene migrated from ENSG00000102144 to ENSG00000102144 (gene set migration)
Early-onset Parkinson disease v3.0 PRKCG Gene migrated from ENSG00000126583 to ENSG00000126583 (gene set migration)
Early-onset Parkinson disease v3.0 ATP6AP2 Gene migrated from ENSG00000182220 to ENSG00000182220 (gene set migration)
Early-onset Parkinson disease v3.0 QDPR Gene migrated from ENSG00000151552 to ENSG00000151552 (gene set migration)
Early-onset Parkinson disease v3.0 SCN1A Gene migrated from ENSG00000144285 to ENSG00000144285 (gene set migration)
Early-onset Parkinson disease v3.0 SERAC1 Gene migrated from ENSG00000122335 to ENSG00000122335 (gene set migration)
Early-onset Parkinson disease v3.0 SLC19A3 Gene migrated from ENSG00000135917 to ENSG00000135917 (gene set migration)
Early-onset Parkinson disease v3.0 SLC18A2 Gene migrated from ENSG00000165646 to ENSG00000165646 (gene set migration)
Early-onset Parkinson disease v3.0 SOX6 Gene migrated from ENSG00000110693 to ENSG00000110693 (gene set migration)
Early-onset Parkinson disease v3.0 SPG7 Gene migrated from ENSG00000197912 to ENSG00000197912 (gene set migration)
Early-onset Parkinson disease v3.0 STUB1 Gene migrated from ENSG00000103266 to ENSG00000103266 (gene set migration)
Early-onset Parkinson disease v3.0 STXBP1 Gene migrated from ENSG00000136854 to ENSG00000136854 (gene set migration)
Early-onset Parkinson disease v3.0 TBC1D24 Gene migrated from ENSG00000162065 to ENSG00000162065 (gene set migration)
Early-onset Parkinson disease v3.0 UBTF Gene migrated from ENSG00000108312 to ENSG00000108312 (gene set migration)
Early-onset Parkinson disease v3.0 VAC14 Gene migrated from ENSG00000103043 to ENSG00000103043 (gene set migration)
Early-onset Parkinson disease v3.0 VPS13C Gene migrated from ENSG00000129003 to ENSG00000129003 (gene set migration)
Early-onset Parkinson disease v3.0 PTS Gene migrated from ENSG00000150787 to ENSG00000150787 (gene set migration)
Early-onset Parkinson disease v3.0 ATP7B Gene migrated from ENSG00000123191 to ENSG00000123191 (gene set migration)
Early-onset Parkinson disease v3.0 CHCHD2 Gene migrated from ENSG00000106153 to ENSG00000106153 (gene set migration)
Early-onset Parkinson disease v3.0 RAB32 Gene migrated from ENSG00000118508 to ENSG00000118508 (gene set migration)
Early-onset Parkinson disease v3.0 WARS2 Gene migrated from ENSG00000116874 to ENSG00000116874 (gene set migration)
Early-onset Parkinson disease v3.0 ZFYVE26 Gene migrated from ENSG00000072121 to ENSG00000072121 (gene set migration)
Early-onset Parkinson disease v3.0 PDE8B Gene migrated from ENSG00000113231 to ENSG00000113231 (gene set migration)
Early-onset Parkinson disease v3.0 DNAJC12 Gene migrated from ENSG00000108176 to ENSG00000108176 (gene set migration)
Early-onset Parkinson disease v3.0 CP Gene migrated from ENSG00000047457 to ENSG00000047457 (gene set migration)
Early-onset Parkinson disease v3.0 KMT2B Gene migrated from ENSG00000272333 to ENSG00000272333 (gene set migration)
Early-onset Parkinson disease v3.0 GBA1 Gene symbol changed from GBA to GBA1 during gene set migration (ENSG00000177628 -> ENSG00000177628)
Early-onset Parkinson disease v3.0 FRRS1L Gene migrated from ENSG00000260230 to ENSG00000260230 (gene set migration)
Early-onset Parkinson disease v3.0 ADAR Gene migrated from ENSG00000160710 to ENSG00000160710 (gene set migration)
Early-onset Parkinson disease v3.0 NR4A2 Gene migrated from ENSG00000153234 to ENSG00000153234 (gene set migration)
Early-onset Parkinson disease v3.0 MYORG Gene symbol changed from KIAA1161 to MYORG during gene set migration (ENSG00000164976 -> ENSG00000164976)
Early-onset Parkinson disease v3.0 AOPEP Gene symbol changed from C9orf3 to AOPEP during gene set migration (ENSG00000148120 -> ENSG00000148120)
Early-onset Parkinson disease v3.0 TPP1 Gene migrated from ENSG00000166340 to ENSG00000166340 (gene set migration)
Early-onset Parkinson disease v3.0 CYP27A1 Gene migrated from ENSG00000135929 to ENSG00000135929 (gene set migration)
Early-onset Parkinson disease v3.0 DCTN1 Gene migrated from ENSG00000204843 to ENSG00000204843 (gene set migration)
Early-onset Parkinson disease v3.0 DNAJC5 Gene migrated from ENSG00000101152 to ENSG00000101152 (gene set migration)
Early-onset Parkinson disease v3.0 POLR3A Gene migrated from ENSG00000148606 to ENSG00000148606 (gene set migration)
Early-onset Parkinson disease v3.0 SLC9A6 Gene migrated from ENSG00000198689 to ENSG00000198689 (gene set migration)
Early-onset Parkinson disease v3.0 WDR45 Gene migrated from ENSG00000196998 to ENSG00000196998 (gene set migration)
Early-onset Parkinson disease v3.0 TH Gene migrated from ENSG00000180176 to ENSG00000180176 (gene set migration)
Early-onset Parkinson disease v3.0 SPR Gene migrated from ENSG00000116096 to ENSG00000116096 (gene set migration)
Early-onset Parkinson disease v3.0 SLC30A10 Gene migrated from ENSG00000196660 to ENSG00000196660 (gene set migration)
Early-onset Parkinson disease v3.0 SPG11 Gene migrated from ENSG00000104133 to ENSG00000104133 (gene set migration)
Early-onset Parkinson disease v3.0 RAB39B Gene migrated from ENSG00000155961 to ENSG00000155961 (gene set migration)
Early-onset Parkinson disease v3.0 PSMF1 Gene migrated from ENSG00000125818 to ENSG00000125818 (gene set migration)
Early-onset Parkinson disease v3.0 PSEN1 Gene migrated from ENSG00000080815 to ENSG00000080815 (gene set migration)
Early-onset Parkinson disease v3.0 PRKN Gene migrated from ENSG00000185345 to ENSG00000185345 (gene set migration)
Early-onset Parkinson disease v3.0 MAPT Gene migrated from ENSG00000186868 to ENSG00000186868 (gene set migration)
Early-onset Parkinson disease v3.0 VCP Gene migrated from ENSG00000165280 to ENSG00000165280 (gene set migration)
Early-onset Parkinson disease v3.0 LYST Gene migrated from ENSG00000143669 to ENSG00000143669 (gene set migration)
Early-onset Parkinson disease v3.0 VPS13A Gene migrated from ENSG00000197969 to ENSG00000197969 (gene set migration)
Early-onset Parkinson disease v3.0 LRRK2 Gene migrated from ENSG00000188906 to ENSG00000188906 (gene set migration)
Early-onset Parkinson disease v3.0 SLC39A14 Gene migrated from ENSG00000104635 to ENSG00000104635 (gene set migration)
Early-onset Parkinson disease v3.0 PANK2 Gene migrated from ENSG00000125779 to ENSG00000125779 (gene set migration)
Early-onset Parkinson disease v3.0 POLG Gene migrated from ENSG00000140521 to ENSG00000140521 (gene set migration)
Early-onset Parkinson disease v3.0 GRN Gene migrated from ENSG00000030582 to ENSG00000030582 (gene set migration)
Early-onset Parkinson disease v3.0 PRKRA Gene migrated from ENSG00000180228 to ENSG00000180228 (gene set migration)
Early-onset Parkinson disease v3.0 PRNP Gene migrated from ENSG00000171867 to ENSG00000171867 (gene set migration)
Early-onset Parkinson disease v3.0 PPP2R5D Gene migrated from ENSG00000112640 to ENSG00000112640 (gene set migration)
Early-onset Parkinson disease v3.0 PTRHD1 Gene migrated from ENSG00000184924 to ENSG00000184924 (gene set migration)
Early-onset Parkinson disease v3.0 FTL Gene migrated from ENSG00000087086 to ENSG00000087086 (gene set migration)
Early-onset Parkinson disease v3.0 FBXO7 Gene migrated from ENSG00000100225 to ENSG00000100225 (gene set migration)
Early-onset Parkinson disease v3.0 DNAJC6 Gene migrated from ENSG00000116675 to ENSG00000116675 (gene set migration)
Early-onset Parkinson disease v3.0 CSF1R Gene migrated from ENSG00000182578 to ENSG00000182578 (gene set migration)
Early-onset Parkinson disease v3.0 C19orf12 Gene migrated from ENSG00000131943 to ENSG00000131943 (gene set migration)
Early-onset Parkinson disease v3.0 ATP1A3 Gene migrated from ENSG00000105409 to ENSG00000105409 (gene set migration)
Early-onset Parkinson disease v3.0 ATP13A2 Gene migrated from ENSG00000159363 to ENSG00000159363 (gene set migration)
Early-onset Parkinson disease v3.0 DAGLB Gene migrated from ENSG00000164535 to ENSG00000164535 (gene set migration)
Early-onset Parkinson disease v3.0 SYNJ1 Gene migrated from ENSG00000159082 to ENSG00000159082 (gene set migration)
Early-onset Parkinson disease v3.0 VPS35 Gene migrated from ENSG00000069329 to ENSG00000069329 (gene set migration)
Early-onset Parkinson disease v3.0 PSAP Gene migrated from ENSG00000197746 to ENSG00000197746 (gene set migration)
Early-onset Parkinson disease v3.0 XPR1 Gene migrated from ENSG00000143324 to ENSG00000143324 (gene set migration)
Early-onset Parkinson disease v3.0 TWNK Gene migrated from ENSG00000107815 to ENSG00000107815 (gene set migration)
Early-onset Parkinson disease v3.0 EIF2AK2 Gene migrated from ENSG00000055332 to ENSG00000055332 (gene set migration)
Early-onset Parkinson disease v3.0 FOXG1 Gene migrated from ENSG00000176165 to ENSG00000176165 (gene set migration)
Early-onset Parkinson disease v3.0 PARK7 Gene migrated from ENSG00000116288 to ENSG00000116288 (gene set migration)
Early-onset Parkinson disease v3.0 PLA2G6 Gene migrated from ENSG00000184381 to ENSG00000184381 (gene set migration)
Early-onset Parkinson disease v3.0 Panel migrated to gene set Ensemblv115. Source version: v2.55
Motor Neurone Disease v2.0 ATXN2_SCA2_CAG STR ATXN2_SCA2_CAG: gene migrated from ENSG00000204842 to ENSG00000204842 (gene set migration)
Motor Neurone Disease v2.0 C9orf72_FTDALS_GGGGCC STR C9orf72_FTDALS_GGGGCC: gene migrated from ENSG00000147894 to ENSG00000147894 (gene set migration)
Motor Neurone Disease v2.0 AR_SBMA_CAG STR AR_SBMA_CAG: gene migrated from ENSG00000169083 to ENSG00000169083 (gene set migration)
Motor Neurone Disease v2.0 LRP12_ALS_CGG STR LRP12_ALS_CGG: gene migrated from ENSG00000147650 to ENSG00000147650 (gene set migration)
Motor Neurone Disease v2.0 NEFH Gene migrated from ENSG00000100285 to ENSG00000100285 (gene set migration)
Motor Neurone Disease v2.0 TRIP4 Gene migrated from ENSG00000103671 to ENSG00000103671 (gene set migration)
Motor Neurone Disease v2.0 ARPP21 Gene migrated from ENSG00000172995 to ENSG00000172995 (gene set migration)
Motor Neurone Disease v2.0 EXOSC8 Gene migrated from ENSG00000120699 to ENSG00000120699 (gene set migration)
Motor Neurone Disease v2.0 IGHMBP2 Gene migrated from ENSG00000132740 to ENSG00000132740 (gene set migration)
Motor Neurone Disease v2.0 EWSR1 Gene migrated from ENSG00000182944 to ENSG00000182944 (gene set migration)
Motor Neurone Disease v2.0 GNE Gene migrated from ENSG00000159921 to ENSG00000159921 (gene set migration)
Motor Neurone Disease v2.0 SLC52A1 Gene migrated from ENSG00000132517 to ENSG00000132517 (gene set migration)
Motor Neurone Disease v2.0 TRPV4 Gene migrated from ENSG00000111199 to ENSG00000111199 (gene set migration)
Motor Neurone Disease v2.0 UBA1 Gene migrated from ENSG00000130985 to ENSG00000130985 (gene set migration)
Motor Neurone Disease v2.0 PCP4 Gene migrated from ENSG00000183036 to ENSG00000183036 (gene set migration)
Motor Neurone Disease v2.0 ASAH1 Gene migrated from ENSG00000104763 to ENSG00000104763 (gene set migration)
Motor Neurone Disease v2.0 ATP7A Gene migrated from ENSG00000165240 to ENSG00000165240 (gene set migration)
Motor Neurone Disease v2.0 ERLIN1 Gene migrated from ENSG00000107566 to ENSG00000107566 (gene set migration)
Motor Neurone Disease v2.0 AIFM1 Gene migrated from ENSG00000156709 to ENSG00000156709 (gene set migration)
Motor Neurone Disease v2.0 RAPGEF2 Gene migrated from ENSG00000109756 to ENSG00000109756 (gene set migration)
Motor Neurone Disease v2.0 LAS1L Gene migrated from ENSG00000001497 to ENSG00000001497 (gene set migration)
Motor Neurone Disease v2.0 BICD2 Gene migrated from ENSG00000185963 to ENSG00000185963 (gene set migration)
Motor Neurone Disease v2.0 DYNC1H1 Gene migrated from ENSG00000197102 to ENSG00000197102 (gene set migration)
Motor Neurone Disease v2.0 PLEKHG5 Gene migrated from ENSG00000171680 to ENSG00000171680 (gene set migration)
Motor Neurone Disease v2.0 DAO Gene migrated from ENSG00000110887 to ENSG00000110887 (gene set migration)
Motor Neurone Disease v2.0 DNAJC7 Gene migrated from ENSG00000168259 to ENSG00000168259 (gene set migration)
Motor Neurone Disease v2.0 CYLD Gene migrated from ENSG00000083799 to ENSG00000083799 (gene set migration)
Motor Neurone Disease v2.0 SQSTM1 Gene migrated from ENSG00000161011 to ENSG00000161011 (gene set migration)
Motor Neurone Disease v2.0 LGALSL Gene migrated from ENSG00000119862 to ENSG00000119862 (gene set migration)
Motor Neurone Disease v2.0 HNRNPA2B1 Gene migrated from ENSG00000122566 to ENSG00000122566 (gene set migration)
Motor Neurone Disease v2.0 FIG4 Gene migrated from ENSG00000112367 to ENSG00000112367 (gene set migration)
Motor Neurone Disease v2.0 ANG Gene migrated from ENSG00000214274 to ENSG00000214274 (gene set migration)
Motor Neurone Disease v2.0 CCNF Gene migrated from ENSG00000162063 to ENSG00000162063 (gene set migration)
Motor Neurone Disease v2.0 VRK1 Gene migrated from ENSG00000100749 to ENSG00000100749 (gene set migration)
Motor Neurone Disease v2.0 TIA1 Gene migrated from ENSG00000116001 to ENSG00000116001 (gene set migration)
Motor Neurone Disease v2.0 PRPH Gene migrated from ENSG00000135406 to ENSG00000135406 (gene set migration)
Motor Neurone Disease v2.0 RBMX Gene migrated from ENSG00000147274 to ENSG00000147274 (gene set migration)
Motor Neurone Disease v2.0 RNF13 Gene migrated from ENSG00000082996 to ENSG00000082996 (gene set migration)
Motor Neurone Disease v2.0 UBQLN4 Gene migrated from ENSG00000160803 to ENSG00000160803 (gene set migration)
Motor Neurone Disease v2.0 TAF15 Gene migrated from ENSG00000270647 to ENSG00000270647 (gene set migration)
Motor Neurone Disease v2.0 SS18L1 Gene migrated from ENSG00000184402 to ENSG00000184402 (gene set migration)
Motor Neurone Disease v2.0 PCDHA9 Gene migrated from ENSG00000204961 to ENSG00000204961 (gene set migration)
Motor Neurone Disease v2.0 GLT8D1 Gene migrated from ENSG00000016864 to ENSG00000016864 (gene set migration)
Motor Neurone Disease v2.0 NEK1 Gene migrated from ENSG00000137601 to ENSG00000137601 (gene set migration)
Motor Neurone Disease v2.0 CHCHD10 Gene migrated from ENSG00000250479 to ENSG00000250479 (gene set migration)
Motor Neurone Disease v2.0 ERBB4 Gene migrated from ENSG00000178568 to ENSG00000178568 (gene set migration)
Motor Neurone Disease v2.0 SLC52A3 Gene migrated from ENSG00000101276 to ENSG00000101276 (gene set migration)
Motor Neurone Disease v2.0 SPG7 Gene migrated from ENSG00000197912 to ENSG00000197912 (gene set migration)
Motor Neurone Disease v2.0 ANXA11 Gene migrated from ENSG00000122359 to ENSG00000122359 (gene set migration)
Motor Neurone Disease v2.0 SPAST Gene migrated from ENSG00000021574 to ENSG00000021574 (gene set migration)
Motor Neurone Disease v2.0 REEP1 Gene migrated from ENSG00000068615 to ENSG00000068615 (gene set migration)
Motor Neurone Disease v2.0 GBE1 Gene migrated from ENSG00000114480 to ENSG00000114480 (gene set migration)
Motor Neurone Disease v2.0 BSCL2 Gene migrated from ENSG00000168000 to ENSG00000168000 (gene set migration)
Motor Neurone Disease v2.0 ATL1 Gene migrated from ENSG00000198513 to ENSG00000198513 (gene set migration)
Motor Neurone Disease v2.0 SPART Gene migrated from ENSG00000133104 to ENSG00000133104 (gene set migration)
Motor Neurone Disease v2.0 SOD1 Gene migrated from ENSG00000142168 to ENSG00000142168 (gene set migration)
Motor Neurone Disease v2.0 SLC52A2 Gene migrated from ENSG00000185803 to ENSG00000185803 (gene set migration)
Motor Neurone Disease v2.0 SIGMAR1 Gene migrated from ENSG00000147955 to ENSG00000147955 (gene set migration)
Motor Neurone Disease v2.0 DCTN1 Gene migrated from ENSG00000204843 to ENSG00000204843 (gene set migration)
Motor Neurone Disease v2.0 HNRNPA1 Gene migrated from ENSG00000135486 to ENSG00000135486 (gene set migration)
Motor Neurone Disease v2.0 KIF5A Gene migrated from ENSG00000155980 to ENSG00000155980 (gene set migration)
Motor Neurone Disease v2.0 ALS2 Gene migrated from ENSG00000003393 to ENSG00000003393 (gene set migration)
Motor Neurone Disease v2.0 ASCC1 Gene migrated from ENSG00000138303 to ENSG00000138303 (gene set migration)
Motor Neurone Disease v2.0 SMN1 Gene migrated from ENSG00000172062 to ENSG00000172062 (gene set migration)
Motor Neurone Disease v2.0 SPTLC1 Gene migrated from ENSG00000090054 to ENSG00000090054 (gene set migration)
Motor Neurone Disease v2.0 PFN1 Gene migrated from ENSG00000108518 to ENSG00000108518 (gene set migration)
Motor Neurone Disease v2.0 GRN Gene migrated from ENSG00000030582 to ENSG00000030582 (gene set migration)
Motor Neurone Disease v2.0 CHMP2B Gene migrated from ENSG00000083937 to ENSG00000083937 (gene set migration)
Motor Neurone Disease v2.0 MATR3 Gene migrated from ENSG00000015479 to ENSG00000015479 (gene set migration)
Motor Neurone Disease v2.0 DNAJB2 Gene migrated from ENSG00000135924 to ENSG00000135924 (gene set migration)
Motor Neurone Disease v2.0 FUS Gene migrated from ENSG00000089280 to ENSG00000089280 (gene set migration)
Motor Neurone Disease v2.0 SETX Gene migrated from ENSG00000107290 to ENSG00000107290 (gene set migration)
Motor Neurone Disease v2.0 SPG11 Gene migrated from ENSG00000104133 to ENSG00000104133 (gene set migration)
Motor Neurone Disease v2.0 TARDBP Gene migrated from ENSG00000120948 to ENSG00000120948 (gene set migration)
Motor Neurone Disease v2.0 UBQLN2 Gene migrated from ENSG00000188021 to ENSG00000188021 (gene set migration)
Motor Neurone Disease v2.0 TBK1 Gene migrated from ENSG00000183735 to ENSG00000183735 (gene set migration)
Motor Neurone Disease v2.0 VAPB Gene migrated from ENSG00000124164 to ENSG00000124164 (gene set migration)
Motor Neurone Disease v2.0 VCP Gene migrated from ENSG00000165280 to ENSG00000165280 (gene set migration)
Motor Neurone Disease v2.0 OPTN Gene migrated from ENSG00000123240 to ENSG00000123240 (gene set migration)
Motor Neurone Disease v2.0 TUBA4A Gene migrated from ENSG00000127824 to ENSG00000127824 (gene set migration)
Motor Neurone Disease v2.0 ERLIN2 Gene migrated from ENSG00000147475 to ENSG00000147475 (gene set migration)
Motor Neurone Disease v2.0 HEXB Gene migrated from ENSG00000049860 to ENSG00000049860 (gene set migration)
Motor Neurone Disease v2.0 HEXA Gene migrated from ENSG00000213614 to ENSG00000213614 (gene set migration)
Motor Neurone Disease v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.49
Early-onset Dementia v2.0 ATN1_DRPLA_CAG STR ATN1_DRPLA_CAG: gene migrated from ENSG00000111676 to ENSG00000111676 (gene set migration)
Early-onset Dementia v2.0 NOTCH2NLC_NIID_GGC STR NOTCH2NLC_NIID_GGC: gene migrated from ENSG00000286219 to ENSG00000286219 (gene set migration)
Early-onset Dementia v2.0 TBP_SCA17_CAG STR TBP_SCA17_CAG: gene migrated from ENSG00000112592 to ENSG00000112592 (gene set migration)
Early-onset Dementia v2.0 PRNP_CJD_octapeptide STR PRNP_CJD_octapeptide: gene migrated from ENSG00000171867 to ENSG00000171867 (gene set migration)
Early-onset Dementia v2.0 C9orf72_FTDALS_GGGGCC STR C9orf72_FTDALS_GGGGCC: gene migrated from ENSG00000147894 to ENSG00000147894 (gene set migration)
Early-onset Dementia v2.0 JPH3_HDL2_CTG STR JPH3_HDL2_CTG: gene migrated from ENSG00000154118 to ENSG00000154118 (gene set migration)
Early-onset Dementia v2.0 ATN1 Gene migrated from ENSG00000111676 to ENSG00000111676 (gene set migration)
Early-onset Dementia v2.0 C9orf72 Gene migrated from ENSG00000147894 to ENSG00000147894 (gene set migration)
Early-onset Dementia v2.0 PRKCH Gene migrated from ENSG00000027075 to ENSG00000027075 (gene set migration)
Early-onset Dementia v2.0 SPART Gene migrated from ENSG00000133104 to ENSG00000133104 (gene set migration)
Early-onset Dementia v2.0 ALS2 Gene migrated from ENSG00000003393 to ENSG00000003393 (gene set migration)
Early-onset Dementia v2.0 GSN Gene migrated from ENSG00000148180 to ENSG00000148180 (gene set migration)
Early-onset Dementia v2.0 TH Gene migrated from ENSG00000180176 to ENSG00000180176 (gene set migration)
Early-onset Dementia v2.0 HTRA2 Gene migrated from ENSG00000115317 to ENSG00000115317 (gene set migration)
Early-onset Dementia v2.0 PPIA Gene migrated from ENSG00000196262 to ENSG00000196262 (gene set migration)
Early-onset Dementia v2.0 ATP7B Gene migrated from ENSG00000123191 to ENSG00000123191 (gene set migration)
Early-onset Dementia v2.0 SOD1 Gene migrated from ENSG00000142168 to ENSG00000142168 (gene set migration)
Early-onset Dementia v2.0 SETX Gene migrated from ENSG00000107290 to ENSG00000107290 (gene set migration)
Early-onset Dementia v2.0 GCH1 Gene migrated from ENSG00000131979 to ENSG00000131979 (gene set migration)
Early-onset Dementia v2.0 SNCB Gene migrated from ENSG00000074317 to ENSG00000074317 (gene set migration)
Early-onset Dementia v2.0 UCHL1 Gene migrated from ENSG00000154277 to ENSG00000154277 (gene set migration)
Early-onset Dementia v2.0 FIG4 Gene migrated from ENSG00000112367 to ENSG00000112367 (gene set migration)
Early-onset Dementia v2.0 ANG Gene migrated from ENSG00000214274 to ENSG00000214274 (gene set migration)
Early-onset Dementia v2.0 TET2 Gene migrated from ENSG00000168769 to ENSG00000168769 (gene set migration)
Early-onset Dementia v2.0 VAPB Gene migrated from ENSG00000124164 to ENSG00000124164 (gene set migration)
Early-onset Dementia v2.0 FA2H Gene migrated from ENSG00000103089 to ENSG00000103089 (gene set migration)
Early-onset Dementia v2.0 NR4A2 Gene migrated from ENSG00000153234 to ENSG00000153234 (gene set migration)
Early-onset Dementia v2.0 CYLD Gene migrated from ENSG00000083799 to ENSG00000083799 (gene set migration)
Early-onset Dementia v2.0 POLG Gene migrated from ENSG00000140521 to ENSG00000140521 (gene set migration)
Early-onset Dementia v2.0 COL4A2 Gene migrated from ENSG00000134871 to ENSG00000134871 (gene set migration)
Early-onset Dementia v2.0 HNRNPA1 Gene migrated from ENSG00000135486 to ENSG00000135486 (gene set migration)
Early-onset Dementia v2.0 SORL1 Gene migrated from ENSG00000137642 to ENSG00000137642 (gene set migration)
Early-onset Dementia v2.0 HNRNPA2B1 Gene migrated from ENSG00000122566 to ENSG00000122566 (gene set migration)
Early-onset Dementia v2.0 RBMX Gene migrated from ENSG00000147274 to ENSG00000147274 (gene set migration)
Early-onset Dementia v2.0 CCNF Gene migrated from ENSG00000162063 to ENSG00000162063 (gene set migration)
Early-onset Dementia v2.0 GBA1 Gene symbol changed from GBA to GBA1 during gene set migration (ENSG00000177628 -> ENSG00000177628)
Early-onset Dementia v2.0 TAF15 Gene migrated from ENSG00000270647 to ENSG00000270647 (gene set migration)
Early-onset Dementia v2.0 SQSTM1 Gene migrated from ENSG00000161011 to ENSG00000161011 (gene set migration)
Early-onset Dementia v2.0 KIF5A Gene migrated from ENSG00000155980 to ENSG00000155980 (gene set migration)
Early-onset Dementia v2.0 MATR3 Gene migrated from ENSG00000015479 to ENSG00000015479 (gene set migration)
Early-onset Dementia v2.0 APOE Gene migrated from ENSG00000130203 to ENSG00000130203 (gene set migration)
Early-onset Dementia v2.0 TIA1 Gene migrated from ENSG00000116001 to ENSG00000116001 (gene set migration)
Early-onset Dementia v2.0 FUS Gene migrated from ENSG00000089280 to ENSG00000089280 (gene set migration)
Early-onset Dementia v2.0 FTL Gene migrated from ENSG00000087086 to ENSG00000087086 (gene set migration)
Early-onset Dementia v2.0 CYP27A1 Gene migrated from ENSG00000135929 to ENSG00000135929 (gene set migration)
Early-onset Dementia v2.0 CHCHD10 Gene migrated from ENSG00000250479 to ENSG00000250479 (gene set migration)
Early-onset Dementia v2.0 C19orf12 Gene migrated from ENSG00000131943 to ENSG00000131943 (gene set migration)
Early-onset Dementia v2.0 ARSA Gene migrated from ENSG00000100299 to ENSG00000100299 (gene set migration)
Early-onset Dementia v2.0 ATP13A2 Gene migrated from ENSG00000159363 to ENSG00000159363 (gene set migration)
Early-onset Dementia v2.0 SNCA Gene migrated from ENSG00000145335 to ENSG00000145335 (gene set migration)
Early-onset Dementia v2.0 STUB1 Gene migrated from ENSG00000103266 to ENSG00000103266 (gene set migration)
Early-onset Dementia v2.0 CTSF Gene migrated from ENSG00000174080 to ENSG00000174080 (gene set migration)
Early-onset Dementia v2.0 MAPT Gene migrated from ENSG00000186868 to ENSG00000186868 (gene set migration)
Early-onset Dementia v2.0 PRKN Gene migrated from ENSG00000185345 to ENSG00000185345 (gene set migration)
Early-onset Dementia v2.0 VPS13A Gene migrated from ENSG00000197969 to ENSG00000197969 (gene set migration)
Early-onset Dementia v2.0 VPS35 Gene migrated from ENSG00000069329 to ENSG00000069329 (gene set migration)
Early-onset Dementia v2.0 WDR45 Gene migrated from ENSG00000196998 to ENSG00000196998 (gene set migration)
Early-onset Dementia v2.0 RNF216 Gene migrated from ENSG00000011275 to ENSG00000011275 (gene set migration)
Early-onset Dementia v2.0 HTRA1 Gene migrated from ENSG00000166033 to ENSG00000166033 (gene set migration)
Early-onset Dementia v2.0 CP Gene migrated from ENSG00000047457 to ENSG00000047457 (gene set migration)
Early-onset Dementia v2.0 PARK7 Gene migrated from ENSG00000116288 to ENSG00000116288 (gene set migration)
Early-onset Dementia v2.0 ANXA11 Gene migrated from ENSG00000122359 to ENSG00000122359 (gene set migration)
Early-onset Dementia v2.0 SPG11 Gene migrated from ENSG00000104133 to ENSG00000104133 (gene set migration)
Early-onset Dementia v2.0 DCTN1 Gene migrated from ENSG00000204843 to ENSG00000204843 (gene set migration)
Early-onset Dementia v2.0 DNAJC5 Gene migrated from ENSG00000101152 to ENSG00000101152 (gene set migration)
Early-onset Dementia v2.0 CST3 Gene migrated from ENSG00000101439 to ENSG00000101439 (gene set migration)
Early-onset Dementia v2.0 CAPRIN1 Gene migrated from ENSG00000135387 to ENSG00000135387 (gene set migration)
Early-onset Dementia v2.0 SLC9A6 Gene migrated from ENSG00000198689 to ENSG00000198689 (gene set migration)
Early-onset Dementia v2.0 GLA Gene migrated from ENSG00000102393 to ENSG00000102393 (gene set migration)
Early-onset Dementia v2.0 NOTCH3 Gene migrated from ENSG00000074181 to ENSG00000074181 (gene set migration)
Early-onset Dementia v2.0 COL4A1 Gene migrated from ENSG00000187498 to ENSG00000187498 (gene set migration)
Early-onset Dementia v2.0 TREX1 Gene migrated from ENSG00000213689 to ENSG00000213689 (gene set migration)
Early-onset Dementia v2.0 VPS13C Gene migrated from ENSG00000129003 to ENSG00000129003 (gene set migration)
Early-onset Dementia v2.0 TUBA4A Gene migrated from ENSG00000127824 to ENSG00000127824 (gene set migration)
Early-onset Dementia v2.0 CHMP2B Gene migrated from ENSG00000083937 to ENSG00000083937 (gene set migration)
Early-onset Dementia v2.0 OPTN Gene migrated from ENSG00000123240 to ENSG00000123240 (gene set migration)
Early-onset Dementia v2.0 PSEN2 Gene migrated from ENSG00000143801 to ENSG00000143801 (gene set migration)
Early-onset Dementia v2.0 TBK1 Gene migrated from ENSG00000183735 to ENSG00000183735 (gene set migration)
Early-onset Dementia v2.0 TARDBP Gene migrated from ENSG00000120948 to ENSG00000120948 (gene set migration)
Early-onset Dementia v2.0 TYROBP Gene migrated from ENSG00000011600 to ENSG00000011600 (gene set migration)
Early-onset Dementia v2.0 NHLRC1 Gene migrated from ENSG00000187566 to ENSG00000187566 (gene set migration)
Early-onset Dementia v2.0 PLA2G6 Gene migrated from ENSG00000184381 to ENSG00000184381 (gene set migration)
Early-onset Dementia v2.0 PANK2 Gene migrated from ENSG00000125779 to ENSG00000125779 (gene set migration)
Early-onset Dementia v2.0 PRNP Gene migrated from ENSG00000171867 to ENSG00000171867 (gene set migration)
Early-onset Dementia v2.0 NPC2 Gene migrated from ENSG00000119655 to ENSG00000119655 (gene set migration)
Early-onset Dementia v2.0 PSEN1 Gene migrated from ENSG00000080815 to ENSG00000080815 (gene set migration)
Early-onset Dementia v2.0 UBQLN2 Gene migrated from ENSG00000188021 to ENSG00000188021 (gene set migration)
Early-onset Dementia v2.0 NPC1 Gene migrated from ENSG00000141458 to ENSG00000141458 (gene set migration)
Early-onset Dementia v2.0 VCP Gene migrated from ENSG00000165280 to ENSG00000165280 (gene set migration)
Early-onset Dementia v2.0 GRN Gene migrated from ENSG00000030582 to ENSG00000030582 (gene set migration)
Early-onset Dementia v2.0 EPM2A Gene migrated from ENSG00000112425 to ENSG00000112425 (gene set migration)
Early-onset Dementia v2.0 XK Gene migrated from ENSG00000047597 to ENSG00000047597 (gene set migration)
Early-onset Dementia v2.0 TREM2 Gene migrated from ENSG00000095970 to ENSG00000095970 (gene set migration)
Early-onset Dementia v2.0 APP Gene migrated from ENSG00000142192 to ENSG00000142192 (gene set migration)
Early-onset Dementia v2.0 ITM2B Gene migrated from ENSG00000136156 to ENSG00000136156 (gene set migration)
Early-onset Dementia v2.0 CLN6 Gene migrated from ENSG00000128973 to ENSG00000128973 (gene set migration)
Early-onset Dementia v2.0 TTR Gene migrated from ENSG00000118271 to ENSG00000118271 (gene set migration)
Early-onset Dementia v2.0 SPG21 Gene migrated from ENSG00000090487 to ENSG00000090487 (gene set migration)
Early-onset Dementia v2.0 PINK1 Gene migrated from ENSG00000158828 to ENSG00000158828 (gene set migration)
Early-onset Dementia v2.0 LRRK2 Gene migrated from ENSG00000188906 to ENSG00000188906 (gene set migration)
Early-onset Dementia v2.0 DNMT1 Gene migrated from ENSG00000130816 to ENSG00000130816 (gene set migration)
Early-onset Dementia v2.0 CSF1R Gene migrated from ENSG00000182578 to ENSG00000182578 (gene set migration)
Early-onset Dementia v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.58
Tubulinopathies v2.0 TUBGCP4 Gene migrated from ENSG00000137822 to ENSG00000137822 (gene set migration)
Tubulinopathies v2.0 TUBA8 Gene migrated from ENSG00000183785 to ENSG00000183785 (gene set migration)
Tubulinopathies v2.0 TTL Gene migrated from ENSG00000114999 to ENSG00000114999 (gene set migration)
Tubulinopathies v2.0 TUBA1A Gene migrated from ENSG00000167552 to ENSG00000167552 (gene set migration)
Tubulinopathies v2.0 TUBB2A Gene migrated from ENSG00000137267 to ENSG00000137267 (gene set migration)
Tubulinopathies v2.0 TUBB3 Gene migrated from ENSG00000258947 to ENSG00000258947 (gene set migration)
Tubulinopathies v2.0 TUBB2B Gene migrated from ENSG00000137285 to ENSG00000137285 (gene set migration)
Tubulinopathies v2.0 TUBB Gene migrated from ENSG00000196230 to ENSG00000196230 (gene set migration)
Tubulinopathies v2.0 TUBG1 Gene migrated from ENSG00000131462 to ENSG00000131462 (gene set migration)
Tubulinopathies v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.2
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 STRADA Gene migrated from ENSG00000266173 to ENSG00000266173 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 RHEB Gene migrated from ENSG00000106615 to ENSG00000106615 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 BRAF Gene migrated from ENSG00000157764 to ENSG00000157764 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 AKT3 Gene migrated from ENSG00000117020 to ENSG00000117020 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 TSC1 Gene migrated from ENSG00000165699 to ENSG00000165699 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 NPRL3 Gene migrated from ENSG00000103148 to ENSG00000103148 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 DEPDC5 Gene migrated from ENSG00000100150 to ENSG00000100150 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 SLC35A2 Gene migrated from ENSG00000102100 to ENSG00000102100 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 TSC2 Gene migrated from ENSG00000103197 to ENSG00000103197 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 MTOR Gene migrated from ENSG00000198793 to ENSG00000198793 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 PTEN Gene migrated from ENSG00000171862 to ENSG00000171862 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 NPRL2 Gene migrated from ENSG00000114388 to ENSG00000114388 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 CNTNAP2 Gene migrated from ENSG00000174469 to ENSG00000174469 (gene set migration)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v1.0 Panel migrated to gene set Ensemblv115. Source version: v0.50
Periventricular Grey Matter Heterotopia v2.0 TMTC3 Gene migrated from ENSG00000139324 to ENSG00000139324 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 ERMARD Gene migrated from ENSG00000130023 to ENSG00000130023 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 SYNCRIP Gene migrated from ENSG00000135316 to ENSG00000135316 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 FAT4 Gene migrated from ENSG00000196159 to ENSG00000196159 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 KAT6B Gene migrated from ENSG00000156650 to ENSG00000156650 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 DENR Gene migrated from ENSG00000139726 to ENSG00000139726 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 HNRNPK Gene migrated from ENSG00000165119 to ENSG00000165119 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 ARFGEF2 Gene migrated from ENSG00000124198 to ENSG00000124198 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 NEDD4L Gene migrated from ENSG00000049759 to ENSG00000049759 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 MAP1B Gene migrated from ENSG00000131711 to ENSG00000131711 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 ARF1 Gene migrated from ENSG00000143761 to ENSG00000143761 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 FLNA Gene migrated from ENSG00000196924 to ENSG00000196924 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 DCHS1 Gene migrated from ENSG00000166341 to ENSG00000166341 (gene set migration)
Periventricular Grey Matter Heterotopia v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.3
Polymicrogyria and Schizencephaly v1.0 TMEM216 Gene migrated from ENSG00000187049 to ENSG00000187049 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 EOMES Gene migrated from ENSG00000163508 to ENSG00000163508 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TUBA8 Gene migrated from ENSG00000183785 to ENSG00000183785 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SRPX2 Gene migrated from ENSG00000102359 to ENSG00000102359 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ENO1 Gene migrated from ENSG00000074800 to ENSG00000074800 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 EMX2 Gene migrated from ENSG00000170370 to ENSG00000170370 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SRD5A3 Gene migrated from ENSG00000128039 to ENSG00000128039 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 INTS8 Gene migrated from ENSG00000164941 to ENSG00000164941 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MCF2 Gene migrated from ENSG00000101977 to ENSG00000101977 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SIX3 Gene migrated from ENSG00000138083 to ENSG00000138083 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SHH Gene migrated from ENSG00000164690 to ENSG00000164690 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX11B Gene migrated from ENSG00000131779 to ENSG00000131779 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 CEP83 Gene migrated from ENSG00000173588 to ENSG00000173588 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 DAG1 Gene migrated from ENSG00000173402 to ENSG00000173402 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX10 Gene migrated from ENSG00000157911 to ENSG00000157911 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX26 Gene migrated from ENSG00000215193 to ENSG00000215193 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX3 Gene migrated from ENSG00000034693 to ENSG00000034693 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PI4KA Gene migrated from ENSG00000241973 to ENSG00000241973 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX5 Gene migrated from ENSG00000139197 to ENSG00000139197 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX16 Gene migrated from ENSG00000121680 to ENSG00000121680 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 NSDHL Gene migrated from ENSG00000147383 to ENSG00000147383 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX2 Gene migrated from ENSG00000164751 to ENSG00000164751 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MED25 Gene migrated from ENSG00000104973 to ENSG00000104973 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SMO Gene migrated from ENSG00000128602 to ENSG00000128602 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 L1CAM Gene migrated from ENSG00000198910 to ENSG00000198910 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 COL4A2 Gene migrated from ENSG00000134871 to ENSG00000134871 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PAX6 Gene migrated from ENSG00000007372 to ENSG00000007372 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 NHEJ1 Gene migrated from ENSG00000187736 to ENSG00000187736 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 FIG4 Gene migrated from ENSG00000112367 to ENSG00000112367 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX14 Gene migrated from ENSG00000142655 to ENSG00000142655 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX13 Gene migrated from ENSG00000162928 to ENSG00000162928 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX12 Gene migrated from ENSG00000108733 to ENSG00000108733 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 AHI1 Gene migrated from ENSG00000135541 to ENSG00000135541 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ASTN1 Gene migrated from ENSG00000152092 to ENSG00000152092 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX19 Gene migrated from ENSG00000162735 to ENSG00000162735 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MFN2 Gene migrated from ENSG00000116688 to ENSG00000116688 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 COL4A1 Gene migrated from ENSG00000187498 to ENSG00000187498 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MAPK8IP3 Gene migrated from ENSG00000138834 to ENSG00000138834 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ADGRG1 Gene migrated from ENSG00000205336 to ENSG00000205336 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RAC3 Gene migrated from ENSG00000169750 to ENSG00000169750 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ATP1A3 Gene migrated from ENSG00000105409 to ENSG00000105409 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 CRNKL1 Gene migrated from ENSG00000101343 to ENSG00000101343 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TMEM161B Gene migrated from ENSG00000164180 to ENSG00000164180 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RAC1 Gene migrated from ENSG00000136238 to ENSG00000136238 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 NFIA Gene migrated from ENSG00000162599 to ENSG00000162599 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TCP1 Gene migrated from ENSG00000120438 to ENSG00000120438 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 DEPDC5 Gene migrated from ENSG00000100150 to ENSG00000100150 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 COL3A1 Gene migrated from ENSG00000168542 to ENSG00000168542 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 HSD17B4 Gene migrated from ENSG00000133835 to ENSG00000133835 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MAN2C1 Gene migrated from ENSG00000140400 to ENSG00000140400 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 LAMC3 Gene migrated from ENSG00000050555 to ENSG00000050555 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 WDR62 Gene migrated from ENSG00000075702 to ENSG00000075702 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SHMT2 Gene migrated from ENSG00000182199 to ENSG00000182199 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TUBB3 Gene migrated from ENSG00000258947 to ENSG00000258947 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MAST1 Gene migrated from ENSG00000105613 to ENSG00000105613 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 NEDD4L Gene migrated from ENSG00000049759 to ENSG00000049759 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PTEN Gene migrated from ENSG00000171862 to ENSG00000171862 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 KIF5C Gene migrated from ENSG00000168280 to ENSG00000168280 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 GRIN2B Gene migrated from ENSG00000273079 to ENSG00000273079 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 GRIN1 Gene migrated from ENSG00000176884 to ENSG00000176884 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RAB3GAP2 Gene migrated from ENSG00000118873 to ENSG00000118873 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX1 Gene migrated from ENSG00000127980 to ENSG00000127980 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PEX6 Gene migrated from ENSG00000124587 to ENSG00000124587 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SNAP29 Gene migrated from ENSG00000099940 to ENSG00000099940 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 AKT3 Gene migrated from ENSG00000117020 to ENSG00000117020 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TMX2 Gene migrated from ENSG00000213593 to ENSG00000213593 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 SCN3A Gene migrated from ENSG00000153253 to ENSG00000153253 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 MAP1B Gene migrated from ENSG00000131711 to ENSG00000131711 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 KIFBP Gene symbol changed from KIF1BP to KIFBP during gene set migration (ENSG00000198954 -> ENSG00000198954)
Polymicrogyria and Schizencephaly v1.0 COL18A1 Gene migrated from ENSG00000182871 to ENSG00000182871 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 GPSM2 Gene migrated from ENSG00000121957 to ENSG00000121957 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 CCND2 Gene migrated from ENSG00000118971 to ENSG00000118971 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 CSMD1 Gene migrated from ENSG00000183117 to ENSG00000183117 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 BICD2 Gene migrated from ENSG00000185963 to ENSG00000185963 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TUBA1A Gene migrated from ENSG00000167552 to ENSG00000167552 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RAB18 Gene migrated from ENSG00000099246 to ENSG00000099246 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 EML1 Gene migrated from ENSG00000066629 to ENSG00000066629 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ATP1A2 Gene migrated from ENSG00000018625 to ENSG00000018625 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 KIF26A Gene migrated from ENSG00000066735 to ENSG00000066735 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RTTN Gene migrated from ENSG00000176225 to ENSG00000176225 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PIK3R2 Gene migrated from ENSG00000105647 to ENSG00000105647 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 PIK3CA Gene migrated from ENSG00000121879 to ENSG00000121879 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 OCLN Gene migrated from ENSG00000197822 to ENSG00000197822 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 NDE1 Gene migrated from ENSG00000072864 to ENSG00000072864 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 DYNC1H1 Gene migrated from ENSG00000197102 to ENSG00000197102 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 ARX Gene migrated from ENSG00000004848 to ENSG00000004848 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TUBB2B Gene migrated from ENSG00000137285 to ENSG00000137285 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 TUBB Gene migrated from ENSG00000196230 to ENSG00000196230 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 RAB3GAP1 Gene migrated from ENSG00000115839 to ENSG00000115839 (gene set migration)
Polymicrogyria and Schizencephaly v1.0 Panel migrated to gene set Ensemblv115. Source version: v0.208
Lissencephaly and Band Heterotopia v2.0 ISCA-37430-Loss Region ISCA-37430-Loss migrated (gene set migration)
Lissencephaly and Band Heterotopia v2.0 BICD2 Gene migrated from ENSG00000185963 to ENSG00000185963 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CLASP1 Gene migrated from ENSG00000074054 to ENSG00000074054 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 SRD5A3 Gene migrated from ENSG00000128039 to ENSG00000128039 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 B3GNT2 Gene migrated from ENSG00000170340 to ENSG00000170340 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 BAIAP2 Gene migrated from ENSG00000175866 to ENSG00000175866 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 TMX2 Gene migrated from ENSG00000213593 to ENSG00000213593 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 GMPPB Gene migrated from ENSG00000173540 to ENSG00000173540 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 NSDHL Gene migrated from ENSG00000147383 to ENSG00000147383 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CSNK2A1 Gene migrated from ENSG00000101266 to ENSG00000101266 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 MFN2 Gene migrated from ENSG00000116688 to ENSG00000116688 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 KIF2A Gene migrated from ENSG00000068796 to ENSG00000068796 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 DYNC1H1 Gene migrated from ENSG00000197102 to ENSG00000197102 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 DCX Gene migrated from ENSG00000077279 to ENSG00000077279 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 B3GALNT2 Gene migrated from ENSG00000162885 to ENSG00000162885 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 KATNB1 Gene migrated from ENSG00000140854 to ENSG00000140854 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 TUBGCP2 Gene migrated from ENSG00000130640 to ENSG00000130640 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 SNAP29 Gene migrated from ENSG00000099940 to ENSG00000099940 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 DCHS1 Gene migrated from ENSG00000166341 to ENSG00000166341 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 OSGEP Gene migrated from ENSG00000092094 to ENSG00000092094 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CRADD Gene migrated from ENSG00000169372 to ENSG00000169372 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 ASPM Gene migrated from ENSG00000066279 to ENSG00000066279 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 ACTG1 Gene migrated from ENSG00000184009 to ENSG00000184009 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 ACTB Gene migrated from ENSG00000075624 to ENSG00000075624 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 VLDLR Gene migrated from ENSG00000147852 to ENSG00000147852 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 ARX Gene migrated from ENSG00000004848 to ENSG00000004848 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 LARGE1 Gene migrated from ENSG00000133424 to ENSG00000133424 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 NDE1 Gene migrated from ENSG00000072864 to ENSG00000072864 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CDK5 Gene migrated from ENSG00000164885 to ENSG00000164885 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CRPPA Gene symbol changed from ISPD to CRPPA during gene set migration (ENSG00000214960 -> ENSG00000214960)
Lissencephaly and Band Heterotopia v2.0 CASP2 Gene migrated from ENSG00000106144 to ENSG00000106144 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CAMSAP1 Gene migrated from ENSG00000130559 to ENSG00000130559 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 LAMB1 Gene migrated from ENSG00000091136 to ENSG00000091136 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 RXYLT1 Gene symbol changed from TMEM5 to RXYLT1 during gene set migration (ENSG00000118600 -> ENSG00000118600)
Lissencephaly and Band Heterotopia v2.0 KIF5C Gene migrated from ENSG00000168280 to ENSG00000168280 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 LAMA2 Gene migrated from ENSG00000196569 to ENSG00000196569 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 APC2 Gene migrated from ENSG00000115266 to ENSG00000115266 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CEP85L Gene migrated from ENSG00000111860 to ENSG00000111860 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 EML1 Gene migrated from ENSG00000066629 to ENSG00000066629 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 TUBA1A Gene migrated from ENSG00000167552 to ENSG00000167552 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 MACF1 Gene migrated from ENSG00000127603 to ENSG00000127603 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 TP73 Gene migrated from ENSG00000078900 to ENSG00000078900 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 PAFAH1B1 Gene migrated from ENSG00000007168 to ENSG00000007168 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 CTNNA2 Gene migrated from ENSG00000066032 to ENSG00000066032 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 RELN Gene migrated from ENSG00000189056 to ENSG00000189056 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 PIDD1 Gene migrated from ENSG00000177595 to ENSG00000177595 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 B4GAT1 Gene migrated from ENSG00000174684 to ENSG00000174684 (gene set migration)
Lissencephaly and Band Heterotopia v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.30
Cobblestone Malformations v2.0 DAG1 Gene migrated from ENSG00000173402 to ENSG00000173402 (gene set migration)
Cobblestone Malformations v2.0 LAMA2 Gene migrated from ENSG00000196569 to ENSG00000196569 (gene set migration)
Cobblestone Malformations v2.0 FKTN Gene migrated from ENSG00000106692 to ENSG00000106692 (gene set migration)
Cobblestone Malformations v2.0 FKRP Gene migrated from ENSG00000181027 to ENSG00000181027 (gene set migration)
Cobblestone Malformations v2.0 LAMB1 Gene migrated from ENSG00000091136 to ENSG00000091136 (gene set migration)
Cobblestone Malformations v2.0 POMGNT2 Gene migrated from ENSG00000144647 to ENSG00000144647 (gene set migration)
Cobblestone Malformations v2.0 RXYLT1 Gene symbol changed from TMEM5 to RXYLT1 during gene set migration (ENSG00000118600 -> ENSG00000118600)
Cobblestone Malformations v2.0 LARGE1 Gene migrated from ENSG00000133424 to ENSG00000133424 (gene set migration)
Cobblestone Malformations v2.0 TMTC3 Gene migrated from ENSG00000139324 to ENSG00000139324 (gene set migration)
Cobblestone Malformations v2.0 COL3A1 Gene migrated from ENSG00000168542 to ENSG00000168542 (gene set migration)
Cobblestone Malformations v2.0 POMT1 Gene migrated from ENSG00000130714 to ENSG00000130714 (gene set migration)
Cobblestone Malformations v2.0 POMGNT1 Gene migrated from ENSG00000085998 to ENSG00000085998 (gene set migration)
Cobblestone Malformations v2.0 POMT2 Gene migrated from ENSG00000009830 to ENSG00000009830 (gene set migration)
Cobblestone Malformations v2.0 Panel migrated to gene set Ensemblv115. Source version: v1.1
Mendeliome v1.5025 PDIA6 Arina Puzriakova commented on gene: PDIA6
Mitochondrial disease v1.25 MT-ATP8 Chern Lim reviewed gene: MT-ATP8: Rating: AMBER; Mode of pathogenicity: None; Publications: 40241304; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL; Current diagnostic: yes
Fetal anomalies v1.588 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.831 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Ciliopathies v1.101 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Cone-rod Dystrophy v0.70 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.831 Sarah Milton Copied gene CLUAP1 from panel Ciliopathies
Intellectual disability syndromic and non-syndromic v1.831 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature,Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Mendeliome v1.5025 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Fetal anomalies v1.588 Sarah Milton Copied gene CLUAP1 from panel Ciliopathies
Fetal anomalies v1.588 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Fetal anomalies. Sources: Expert Review Red,Literature,Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Ciliopathies v1.101 CLUAP1 Sarah Milton Classified gene: CLUAP1 as Red List (low evidence)
Ciliopathies v1.101 CLUAP1 Sarah Milton Gene: cluap1 has been classified as Red List (Low Evidence).
Ciliopathies v1.101 CLUAP1 Sarah Milton Classified gene: CLUAP1 as Red List (low evidence)
Ciliopathies v1.101 CLUAP1 Sarah Milton Gene: cluap1 has been classified as Red List (Low Evidence).
Ciliopathies v1.101 Sarah Milton Added reviews for gene CLUAP1 from panel Cone-rod Dystrophy
Ciliopathies v1.100 Sarah Milton Copied gene CLUAP1 from panel Mendeliome
Ciliopathies v1.100 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Ciliopathies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Cone-rod Dystrophy v0.70 Sarah Milton Copied gene CLUAP1 from panel Mendeliome
Cone-rod Dystrophy v0.70 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Cone-rod Dystrophy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Mendeliome v1.5025 CLUAP1 Sarah Milton Classified gene: CLUAP1 as Amber List (moderate evidence)
Mendeliome v1.5025 CLUAP1 Sarah Milton Gene: cluap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5024 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Review for gene: CLUAP1 was set to AMBER
Added comment: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Mendeliome v1.5023 MAD2L1BP Sangavi Sivagnanasundram gene: MAD2L1BP was added
gene: MAD2L1BP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAD2L1BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAD2L1BP were set to 37796616; 37334967
Phenotypes for gene: MAD2L1BP were set to Female infertility MONDO:0021124; MAD2L1BP-related Mosaic variegated aneuploidy syndrome with microcephaly, epileptic encephalopathy, developmental delay and juvenile granulosa‑cell tumours MONDO:0002254
Review for gene: MAD2L1BP was set to AMBER
Added comment: PMID: 37334967 - this publication doesn't report variants on the MANE select transcript
3 unrelated families reported with biallelic variants in MAD2L1BP presenting with infertility
One family reported consanguinity.
The population frequencies reported in the publication are related to gnomAD v2.1. When looking at gnomAD v4.1, the variants are rare enough for AR association.

PMID: 37796616
Reports two consanguineous families presenting with a complex phenotype including microcephaly, brain malformations (with cysts and polymicrogyria), seizures, developmental delay.

No pathogenic variants reported in ClinVar
No Morbid entry in OMIM
This gene to remain as AMBER for both GDAs given the reports are in consanguineous families and supportive functional assays are required.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.830 Sarah Milton Copied gene PTPRD from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.830 PTPRD Sarah Milton gene: PTPRD was added
gene: PTPRD was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PTPRD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPRD were set to 37056996; 31088393; 38890753
Phenotypes for gene: PTPRD were set to Neurodevelopmental disorder, MONDO:0700092, PTPRD related
Incidentalome v0.437 MBD4 Lucy Spencer Phenotypes for gene: MBD4 were changed from Hereditary neoplastic syndrome, MBD4-associated MONDO:0015356 to Tumor predisposition syndrome 2 MIM#619975; Hereditary neoplastic syndrome, MBD4-associated MONDO:0015356
Mendeliome v1.5022 PTPRD Sarah Milton changed review comment from: PTPRD encodes protein-tyrosine phosphatase, receptor type D.

PMID 31088393 and PMID 37056996 both list PTPRD as a candidate gene for a neurodevelopmental disorder.

PMID 31088393 reports a 5 year old with a de novo canonical splice variant in the gene presenting with moderate non syndromic developmental delay.
PMID 37056996 notes 2 missense variants in the gene in individuals with speech and language delay however minimal variant and phenotypic information are provided.

GWAS studies have previously linked polymorphisms in the gene to ASD/ADHD/OCD.

Supportive functional evidence with loss of PTPRD expression in mice induces aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells.
Sources: Literature; to: PTPRD encodes protein-tyrosine phosphatase, receptor type D.

PMID 31088393 and PMID 37056996 both list PTPRD as a candidate gene for a neurodevelopmental disorder.

PMID 31088393 reports a 5 year old with a de novo canonical splice variant in the gene presenting with moderate non syndromic developmental delay.
PMID 37056996 notes 2 heterozygous missense variants in the gene in individuals with speech and language delay however minimal variant and phenotypic information are provided.
PTPRD is constrained for loss of function with very few heterozygous NMD predicted variants in the population database gnomAD v4.

GWAS studies have previously linked polymorphisms in the gene to ASD/ADHD/OCD.

Supportive functional evidence with loss of PTPRD expression in mice induces aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells.
Sources: Literature
Mendeliome v1.5022 PTPRD Sarah Milton Classified gene: PTPRD as Amber List (moderate evidence)
Mendeliome v1.5022 PTPRD Sarah Milton Gene: ptprd has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5021 PTPRD Sarah Milton gene: PTPRD was added
gene: PTPRD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPRD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPRD were set to 37056996; 31088393; 38890753
Phenotypes for gene: PTPRD were set to Neurodevelopmental disorder, MONDO:0700092, PTPRD related
Review for gene: PTPRD was set to AMBER
Added comment: PTPRD encodes protein-tyrosine phosphatase, receptor type D.

PMID 31088393 and PMID 37056996 both list PTPRD as a candidate gene for a neurodevelopmental disorder.

PMID 31088393 reports a 5 year old with a de novo canonical splice variant in the gene presenting with moderate non syndromic developmental delay.
PMID 37056996 notes 2 missense variants in the gene in individuals with speech and language delay however minimal variant and phenotypic information are provided.

GWAS studies have previously linked polymorphisms in the gene to ASD/ADHD/OCD.

Supportive functional evidence with loss of PTPRD expression in mice induces aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells.
Sources: Literature
Colorectal Cancer and Polyposis v1.5 MBD4 Lucy Spencer Marked gene: MBD4 as ready
Colorectal Cancer and Polyposis v1.5 MBD4 Lucy Spencer Gene: mbd4 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v1.5 MBD4 Lucy Spencer Classified gene: MBD4 as Green List (high evidence)
Colorectal Cancer and Polyposis v1.5 MBD4 Lucy Spencer Gene: mbd4 has been classified as Green List (High Evidence).
Mendeliome v1.5020 SIT1 Zornitza Stark Marked gene: SIT1 as ready
Mendeliome v1.5020 SIT1 Zornitza Stark Gene: sit1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5020 Zornitza Stark Copied gene SIT1 from panel Combined Immunodeficiency
Mendeliome v1.5020 SIT1 Zornitza Stark gene: SIT1 was added
gene: SIT1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIT1 were set to PMID: 42128181
Phenotypes for gene: SIT1 were set to Inborn error of immunity, MONDO:0003778, SIT1-related
Combined Immunodeficiency v1.150 SIT1 Zornitza Stark Marked gene: SIT1 as ready
Combined Immunodeficiency v1.150 SIT1 Zornitza Stark Gene: sit1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.150 SIT1 Zornitza Stark Phenotypes for gene: SIT1 were changed from recalcitrant warts; hodgkins lymphoma to Inborn error of immunity, MONDO:0003778, SIT1-related
Combined Immunodeficiency v1.149 SIT1 Zornitza Stark Classified gene: SIT1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.149 SIT1 Zornitza Stark Gene: sit1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5019 ADAD2 Zornitza Stark Marked gene: ADAD2 as ready
Mendeliome v1.5019 ADAD2 Zornitza Stark Gene: adad2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.180 ADAD2 Zornitza Stark Marked gene: ADAD2 as ready
Infertility and Recurrent Pregnancy Loss v1.180 ADAD2 Zornitza Stark Gene: adad2 has been classified as Green List (High Evidence).
Cholestasis v1.12 CFTR Zornitza Stark Publications for gene: CFTR were set to 25097709
Cholestasis v1.11 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Cholestasis v1.11 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Cholestasis v1.11 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Cholestasis v1.11 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Proteinuria v0.243 SYNPO2 Zornitza Stark Marked gene: SYNPO2 as ready
Proteinuria v0.243 SYNPO2 Zornitza Stark Gene: synpo2 has been classified as Red List (Low Evidence).
Proteinuria v0.243 Zornitza Stark Copied gene SYNPO2 from panel Mendeliome
Proteinuria v0.243 SYNPO2 Zornitza Stark gene: SYNPO2 was added
gene: SYNPO2 was added to Proteinuria. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SYNPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYNPO2 were set to 36847718; 33615072
Phenotypes for gene: SYNPO2 were set to Nephrotic Syndrome MONDO:0005377
Mendeliome v1.5019 SYNPO2 Zornitza Stark Marked gene: SYNPO2 as ready
Mendeliome v1.5019 SYNPO2 Zornitza Stark Gene: synpo2 has been classified as Red List (Low Evidence).
Cholestasis v1.10 CFTR Freeman A reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8813874, 3967446, 22798282, 27806795, 23949094, 24436365, 34510112.; Phenotypes: cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.5019 SYNPO2 Sangavi Sivagnanasundram Classified gene: SYNPO2 as Red List (low evidence)
Mendeliome v1.5019 SYNPO2 Sangavi Sivagnanasundram Gene: synpo2 has been classified as Red List (Low Evidence).
Mendeliome v1.5018 SYNPO2 Sangavi Sivagnanasundram gene: SYNPO2 was added
gene: SYNPO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYNPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYNPO2 were set to 36847718; 33615072
Phenotypes for gene: SYNPO2 were set to Nephrotic Syndrome MONDO:0005377
Review for gene: SYNPO2 was set to RED
Added comment: PMID 33615072 reports two consanguineous families with homozygous loss-of-function SYNPO2 variants (p.Lys1124* and p.Ala1134Thr) presenting with childhood-onset steroid-resistant nephrotic syndrome.

p.Ala1134Thr is present in gnomADv4.1 with a FAF of 1.4% however p.Lys1124* is absent from gnomADv4.1

There are no pathogenic variants reported in ClinVar in this gene and there is no Morbid terminology present in OMIM. Given only one of the reported families present with a rare variant, this GDA is to remain RED till further evidence is provided.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.180 Sarah Milton Copied gene ADAD2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.180 ADAD2 Sarah Milton gene: ADAD2 was added
gene: ADAD2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADAD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAD2 were set to 39267058; 37325547; 36708028; 32741963
Phenotypes for gene: ADAD2 were set to Spermatogenic failure, MONDO:0004983, ADAD2-related
Mendeliome v1.5017 ADAD2 Sarah Milton Classified gene: ADAD2 as Green List (high evidence)
Mendeliome v1.5017 ADAD2 Sarah Milton Gene: adad2 has been classified as Green List (High Evidence).
Mendeliome v1.5016 ADAD2 Sarah Milton gene: ADAD2 was added
gene: ADAD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAD2 were set to 39267058; 37325547; 36708028; 32741963
Phenotypes for gene: ADAD2 were set to Spermatogenic failure, MONDO:0004983, ADAD2-related
Review for gene: ADAD2 was set to GREEN
Added comment: ADAD2 encodes a testis-specific adenosine deaminase domain-containing (ADAD) protein.

PMID 32741963, PMID 36708028, PMID 37325547 and PMID 39267058 report biallelic loss of function/missense variants in ADAD2 in 6 unrelated families (10 individuals). Clinical features included non‑obstructive azoospermia, spermatogonial arrest or severe oligoasthenoteratozoospermia.
Variants were at appropriate carrier frequency in the population database gnomAD v4 for a rare recessive disorder.

Supportive functional studies included mouse knockout recapitulating the spermatogenic failure phenotype and western blot loss of expression.
Sources: Literature
Mendeliome v1.5015 DNAH3 Rylee Peters Marked gene: DNAH3 as ready
Mendeliome v1.5015 DNAH3 Rylee Peters Gene: dnah3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.179 DNAH3 Rylee Peters Marked gene: DNAH3 as ready
Infertility and Recurrent Pregnancy Loss v1.179 DNAH3 Rylee Peters Gene: dnah3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.179 Rylee Peters Copied gene DNAH3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.179 DNAH3 Rylee Peters gene: DNAH3 was added
gene: DNAH3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: DNAH3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH3 were set to 39588341; 39503742; 38312775
Phenotypes for gene: DNAH3 were set to Male infertility, MONDO:0005372, DNAH3-related
Mendeliome v1.5015 DNAH3 Rylee Peters changed review comment from: PMIDs 38312775, 39588341 and 39503742 report nine individuals with biallelic loss‑of‑function DNAH3 variants causing severe asthenoteratozoospermia (multiple morphological abnormalities of the sperm flagella). Functional studies show reduced DNAH3 protein in patient sperm and infertility in Dnah3‑knockout mice.
Sources: Literature; to: PMIDs 38312775, 39588341 and 39503742 report nine individuals with biallelic DNAH3 variants causing severe asthenoteratozoospermia (multiple morphological abnormalities of the sperm flagella). Functional studies show reduced DNAH3 protein in patient sperm and infertility in Dnah3‑knockout mice.
Sources: Literature
Mendeliome v1.5015 DNAH3 Rylee Peters Classified gene: DNAH3 as Green List (high evidence)
Mendeliome v1.5015 DNAH3 Rylee Peters Gene: dnah3 has been classified as Green List (High Evidence).
Mendeliome v1.5014 DNAH3 Rylee Peters gene: DNAH3 was added
gene: DNAH3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH3 were set to 39588341; 39503742; 38312775
Phenotypes for gene: DNAH3 were set to Male infertility, MONDO:0005372, DNAH3-related
Review for gene: DNAH3 was set to GREEN
Added comment: PMIDs 38312775, 39588341 and 39503742 report nine individuals with biallelic loss‑of‑function DNAH3 variants causing severe asthenoteratozoospermia (multiple morphological abnormalities of the sperm flagella). Functional studies show reduced DNAH3 protein in patient sperm and infertility in Dnah3‑knockout mice.
Sources: Literature
Colorectal Cancer and Polyposis v1.4 MBD4 Chern Lim gene: MBD4 was added
gene: MBD4 was added to Colorectal Cancer and Polyposis. Sources: Expert List,Expert Review
Mode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MBD4 were set to Tumor predisposition syndrome 2, MIM#619975
Review for gene: MBD4 was set to GREEN
gene: MBD4 was marked as current diagnostic
Added comment: ClinGen: reviewed for autosomal recessive tumor predisposition syndrome.
This condition is a cancer predisposition syndrome with features such as acute myeloid leukemia, myelodysplastic syndrome, colorectal polyposis and carcinoma. The mechanism of pathogenicity appears to be loss-of-function.

eviQ: biallelic, associated with gastrointestinal polyposis and colorectal cancer.
Sources: Expert List, Expert Review
Combined Immunodeficiency v1.148 SIT1 Peter McNaughton gene: SIT1 was added
gene: SIT1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: SIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIT1 were set to PMID: 42128181
Phenotypes for gene: SIT1 were set to recalcitrant warts; hodgkins lymphoma
Review for gene: SIT1 was set to AMBER
Added comment: 48-year-old male patient presenting with recalcitrant warts, two different Hodgkin’s lymphomas at the age of 26 and 39 and combined immunodeficiency. Findings robustly supported by multimodal data including KO cell model and partial rescue of cellular phenotype with knock in. Amber for single proband.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.178 Bryony Thompson Copied gene ZMYND12 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.178 ZMYND12 Bryony Thompson gene: ZMYND12 was added
gene: ZMYND12 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZMYND12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZMYND12 were set to 39066891; 37934199
Phenotypes for gene: ZMYND12 were set to Infertility disorder, MONDO:0005047
Mendeliome v1.5013 ZMYND12 Bryony Thompson Marked gene: ZMYND12 as ready
Mendeliome v1.5013 ZMYND12 Bryony Thompson Gene: zmynd12 has been classified as Green List (High Evidence).
Mendeliome v1.5013 ZMYND12 Bryony Thompson Classified gene: ZMYND12 as Green List (high evidence)
Mendeliome v1.5013 ZMYND12 Bryony Thompson Gene: zmynd12 has been classified as Green List (High Evidence).
Mendeliome v1.5012 ZMYND12 Bryony Thompson gene: ZMYND12 was added
gene: ZMYND12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZMYND12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZMYND12 were set to 39066891; 37934199
Phenotypes for gene: ZMYND12 were set to Infertility disorder, MONDO:0005047
Review for gene: ZMYND12 was set to GREEN
Added comment: PMID 39066891 and PMID 37934199 report five individuals from five unrelated families with biallelic loss-of-function ZMYND12 variants presenting with severe male infertility, including asthenozoospermia and multiple morphological abnormalities of the sperm flagellum. Affected men exhibit markedly reduced progressive sperm motility and abnormal flagellar morphology leading to primary infertility. Mouse Zmynd12 knockout recapitulates subfertility and reduced sperm velocity, and RNAi knock‑down of the ortholog in Trypanosoma reproduces flagellar motility defects, though rescue experiments are lacking. The recurrent c.433C>T stop‑gain variant occurs in three families across distinct populations, with evidence of independent origins.
Sources: Literature
Mendeliome v1.5011 TPTE2 Bryony Thompson Marked gene: TPTE2 as ready
Mendeliome v1.5011 TPTE2 Bryony Thompson Gene: tpte2 has been classified as Red List (Low Evidence).
Mendeliome v1.5011 TPTE2 Bryony Thompson gene: TPTE2 was added
gene: TPTE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TPTE2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TPTE2 were set to 37056996; 34089056
Phenotypes for gene: TPTE2 were set to Infertility disorder, MONDO:0005047; Neurodevelopmental disorder, MONDO:0700092
Review for gene: TPTE2 was set to RED
Added comment: PMID 34089056 reports 1 individual from 1 family with biallelic loss‑of‑function TPTE2 variants causing severe sperm motility disorder (infertility), while PMID 37056996 reports individuals with de novo heterozygous TPTE2 variants in cases with a neurodevelopmental disorder characterised by speech delay, intellectual disability, motor delay and joint hypermobility. 1 stopgain, 1 UTR, 2 missense - R407W present in 12 cases, which is present in the South Asian population in gnomAD v4 at AF of 0.1325%. Other missense R400I is present in 2 individuals in the other population. Only the stopgain is absent from gnomAD. No other supporting evidence
Sources: Literature
Congenital Heart Defect v0.543 Bryony Thompson Copied gene SOX7 from panel Mendeliome
Congenital Heart Defect v0.543 SOX7 Bryony Thompson gene: SOX7 was added
gene: SOX7 was added to Congenital Heart Defect. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SOX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX7 were set to 35260939; 33720353; 33846290; 35422912; 37406974
Phenotypes for gene: SOX7 were set to congenital heart disease, MONDO:0005453
Mendeliome v1.5010 SOX7 Bryony Thompson Marked gene: SOX7 as ready
Mendeliome v1.5010 SOX7 Bryony Thompson Gene: sox7 has been classified as Green List (High Evidence).
Mendeliome v1.5010 SOX7 Bryony Thompson Classified gene: SOX7 as Green List (high evidence)
Mendeliome v1.5010 SOX7 Bryony Thompson Added comment: Comment on list classification: ClinGen CHD GCEP Limited Classification - 01/10/2024
Mendeliome v1.5010 SOX7 Bryony Thompson Gene: sox7 has been classified as Green List (High Evidence).
Mendeliome v1.5009 SOX7 Bryony Thompson gene: SOX7 was added
gene: SOX7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX7 were set to 35260939; 33720353; 33846290; 35422912; 37406974
Phenotypes for gene: SOX7 were set to congenital heart disease, MONDO:0005453
Review for gene: SOX7 was set to GREEN
Added comment: Across all studies, nine unrelated families (16 cases) with SOX7 variants (8 missense & 1 stopgain). Some of the variants are present in gnomAD v4 but not at frequencies higher than expected for an AD condition. In vitro functional assays and mouse model supporting a monoallelic loss‑of‑function mechanism for non‑syndromic congenital heart disease.
Sources: Literature
Genetic Epilepsy v1.435 TMEM161B Zornitza Stark Marked gene: TMEM161B as ready
Genetic Epilepsy v1.435 TMEM161B Zornitza Stark Gene: tmem161b has been classified as Green List (High Evidence).
Microcephaly v1.444 TMEM161B Zornitza Stark Marked gene: TMEM161B as ready
Microcephaly v1.444 TMEM161B Zornitza Stark Gene: tmem161b has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.208 TMEM161B Zornitza Stark Marked gene: TMEM161B as ready
Polymicrogyria and Schizencephaly v0.208 TMEM161B Zornitza Stark Gene: tmem161b has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.208 Zornitza Stark Copied gene TMEM161B from panel Mendeliome
Polymicrogyria and Schizencephaly v0.208 TMEM161B Zornitza Stark gene: TMEM161B was added
gene: TMEM161B was added to Polymicrogyria and Schizencephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM161B were set to 37486637; 36669109; 36669111
Phenotypes for gene: TMEM161B were set to Neurodevelopmental disorder, MONDO:0700092, TMEM161B-related
Microcephaly v1.444 Zornitza Stark Copied gene TMEM161B from panel Mendeliome
Microcephaly v1.444 TMEM161B Zornitza Stark gene: TMEM161B was added
gene: TMEM161B was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM161B were set to 37486637; 36669109; 36669111
Phenotypes for gene: TMEM161B were set to Neurodevelopmental disorder, MONDO:0700092, TMEM161B-related
Intellectual disability syndromic and non-syndromic v1.829 Zornitza Stark Copied gene TMEM161B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.829 TMEM161B Zornitza Stark gene: TMEM161B was added
gene: TMEM161B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM161B were set to 37486637; 36669109; 36669111
Phenotypes for gene: TMEM161B were set to Neurodevelopmental disorder, MONDO:0700092, TMEM161B-related
Genetic Epilepsy v1.435 Zornitza Stark Copied gene TMEM161B from panel Mendeliome
Genetic Epilepsy v1.435 TMEM161B Zornitza Stark gene: TMEM161B was added
gene: TMEM161B was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM161B were set to 37486637; 36669109; 36669111
Phenotypes for gene: TMEM161B were set to Neurodevelopmental disorder, MONDO:0700092, TMEM161B-related
Mendeliome v1.5008 TMEM161B Zornitza Stark Marked gene: TMEM161B as ready
Mendeliome v1.5008 TMEM161B Zornitza Stark Gene: tmem161b has been classified as Green List (High Evidence).
Mendeliome v1.5008 TMEM161B Zornitza Stark Classified gene: TMEM161B as Green List (high evidence)
Mendeliome v1.5008 TMEM161B Zornitza Stark Gene: tmem161b has been classified as Green List (High Evidence).
Mendeliome v1.5007 TMEM161B Zornitza Stark gene: TMEM161B was added
gene: TMEM161B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM161B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM161B were set to 37486637; 36669109; 36669111
Phenotypes for gene: TMEM161B were set to Neurodevelopmental disorder, MONDO:0700092, TMEM161B-related
Review for gene: TMEM161B was set to GREEN
Added comment: Fifteen individuals from eight families reported with biallelic TMEM161B variants causing diffuse polymicrogyria, seizures, microcephaly, hypotonia and intellectual disability. Functional studies include splice‑site RNA validation, GLI1 luciferase assays, mouse knockout, ferret knock‑down and patient‑derived organoid and fibroblast defects rescued by wild‑type TMEM161B or CDC42 in mouse knock‑in models.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.177 PPP2R1B Zornitza Stark Marked gene: PPP2R1B as ready
Infertility and Recurrent Pregnancy Loss v1.177 PPP2R1B Zornitza Stark Gene: ppp2r1b has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.177 Zornitza Stark Copied gene PPP2R1B from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.177 PPP2R1B Zornitza Stark gene: PPP2R1B was added
gene: PPP2R1B was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PPP2R1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R1B were set to 33913576
Phenotypes for gene: PPP2R1B were set to Infertility disorder, MONDO:0005047, PPP2R1B-related
Mendeliome v1.5006 PPP2R1B Zornitza Stark Marked gene: PPP2R1B as ready
Mendeliome v1.5006 PPP2R1B Zornitza Stark Gene: ppp2r1b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5006 PPP2R1B Zornitza Stark Classified gene: PPP2R1B as Amber List (moderate evidence)
Mendeliome v1.5006 PPP2R1B Zornitza Stark Gene: ppp2r1b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5005 PPP2R1B Zornitza Stark gene: PPP2R1B was added
gene: PPP2R1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R1B were set to 33913576
Phenotypes for gene: PPP2R1B were set to Infertility disorder, MONDO:0005047, PPP2R1B-related
Review for gene: PPP2R1B was set to AMBER
Added comment: PMID 33913576 reports 5 individuals from 3 unrelated families with heterozygous missense PPP2R1B variants causing non‑obstructive azoospermia with meiotic arrest, and an additional individual with Sertoli‑cell‑only syndrome. Affected males present with meiotic arrest leading to infertility; the Sertoli‑cell‑only case shows a distinct histological phenotype. Cellular assays demonstrate reduced protein stability and increased ubiquitination for the meiotic‑arrest variants, whereas the Sertoli‑cell‑only variant shows normal stability. Homozygous deletion of Ppp2r1b in Mus musculus impaired meiotic recombination and caused meiotic arrest in spermatocytes.

All the variants are missense and present in gnomAD, including the p.Arg410His variant in 32 hets. Lack of segregation data. All the variants would be classified as VOUS, hence Amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.828 IRF2BP1 Zornitza Stark Marked gene: IRF2BP1 as ready
Intellectual disability syndromic and non-syndromic v1.828 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.828 IRF2BP1 Zornitza Stark Classified gene: IRF2BP1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.828 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.827 IRF2BP1 Zornitza Stark changed review comment from: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.
Sources: Literature; to: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.

However, all three individuals were identified as part of large cohort studies and I also note LoF variants in gnomAD.

Sources: Literature
Intellectual disability syndromic and non-syndromic v1.827 IRF2BP1 Zornitza Stark edited their review of gene: IRF2BP1: Changed rating: AMBER
Mendeliome v1.5004 IRF2BP1 Zornitza Stark Classified gene: IRF2BP1 as Amber List (moderate evidence)
Mendeliome v1.5004 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5003 IRF2BP1 Zornitza Stark changed review comment from: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.
Sources: Literature; to: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.

However, all three individuals were identified as part of large cohort studies and I also note LoF variants in gnomAD.

Sources: Literature
Mendeliome v1.5003 IRF2BP1 Zornitza Stark edited their review of gene: IRF2BP1: Changed rating: AMBER
Microcephaly v1.443 IRF2BP1 Zornitza Stark Classified gene: IRF2BP1 as Amber List (moderate evidence)
Microcephaly v1.443 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.442 IRF2BP1 Zornitza Stark changed review comment from: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.
Sources: Literature; to: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.

However, all three individuals were identified as part of large cohort studies and I also note LoF variants in gnomAD.

Sources: Literature
Microcephaly v1.442 IRF2BP1 Zornitza Stark edited their review of gene: IRF2BP1: Changed rating: AMBER
Microcephaly v1.442 IRF2BP1 Zornitza Stark Marked gene: IRF2BP1 as ready
Microcephaly v1.442 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Green List (High Evidence).
Microcephaly v1.442 Zornitza Stark Copied gene IRF2BP1 from panel Mendeliome
Microcephaly v1.442 IRF2BP1 Zornitza Stark gene: IRF2BP1 was added
gene: IRF2BP1 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: IRF2BP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP1 were set to 38091987; 37501076
Phenotypes for gene: IRF2BP1 were set to Neurodevelopmental disorder, MONDO:0700092, IRF2BP1-related
Intellectual disability syndromic and non-syndromic v1.827 Zornitza Stark Copied gene IRF2BP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.827 IRF2BP1 Zornitza Stark gene: IRF2BP1 was added
gene: IRF2BP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: IRF2BP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP1 were set to 38091987; 37501076
Phenotypes for gene: IRF2BP1 were set to Neurodevelopmental disorder, MONDO:0700092, IRF2BP1-related
Mendeliome v1.5003 IRF2BP1 Zornitza Stark Marked gene: IRF2BP1 as ready
Mendeliome v1.5003 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Green List (High Evidence).
Mendeliome v1.5003 IRF2BP1 Zornitza Stark Classified gene: IRF2BP1 as Green List (high evidence)
Mendeliome v1.5003 IRF2BP1 Zornitza Stark Gene: irf2bp1 has been classified as Green List (High Evidence).
Mendeliome v1.5002 IRF2BP1 Zornitza Stark gene: IRF2BP1 was added
gene: IRF2BP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRF2BP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP1 were set to 38091987; 37501076
Phenotypes for gene: IRF2BP1 were set to Neurodevelopmental disorder, MONDO:0700092, IRF2BP1-related
Review for gene: IRF2BP1 was set to GREEN
Added comment: PMID 38091987 reports two unrelated individuals with de novo truncating IRF2BP1 variants presenting with neurodevelopmental disorder, severe immunodeficiency, microcephaly and developmental delay, while PMID 37501076 adds a third unrelated individual with a de novo nonsense IRF2BP1 variant causing neonatal‑onset microcephaly, epilepsy, hypotonia and global developmental delay.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.826 DENR Zornitza Stark Marked gene: DENR as ready
Intellectual disability syndromic and non-syndromic v1.826 DENR Zornitza Stark Gene: denr has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.434 DENR Zornitza Stark Marked gene: DENR as ready
Genetic Epilepsy v1.434 DENR Zornitza Stark Gene: denr has been classified as Amber List (Moderate Evidence).
Periventricular Grey Matter Heterotopia v1.3 DENR Zornitza Stark Marked gene: DENR as ready
Periventricular Grey Matter Heterotopia v1.3 DENR Zornitza Stark Gene: denr has been classified as Amber List (Moderate Evidence).
Periventricular Grey Matter Heterotopia v1.3 Zornitza Stark Copied gene DENR from panel Mendeliome
Periventricular Grey Matter Heterotopia v1.3 DENR Zornitza Stark gene: DENR was added
gene: DENR was added to Periventricular Grey Matter Heterotopia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DENR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DENR were set to 27239039
Phenotypes for gene: DENR were set to Neurodevelopmental disorder, MONDO:0700092, DENR-related
Intellectual disability syndromic and non-syndromic v1.826 Zornitza Stark Copied gene DENR from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.826 DENR Zornitza Stark gene: DENR was added
gene: DENR was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DENR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DENR were set to 27239039
Phenotypes for gene: DENR were set to Neurodevelopmental disorder, MONDO:0700092, DENR-related
Genetic Epilepsy v1.434 Zornitza Stark Copied gene DENR from panel Mendeliome
Genetic Epilepsy v1.434 DENR Zornitza Stark gene: DENR was added
gene: DENR was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DENR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DENR were set to 27239039
Phenotypes for gene: DENR were set to Neurodevelopmental disorder, MONDO:0700092, DENR-related
Mendeliome v1.5001 DENR Zornitza Stark Marked gene: DENR as ready
Mendeliome v1.5001 DENR Zornitza Stark Gene: denr has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5001 DENR Zornitza Stark Classified gene: DENR as Amber List (moderate evidence)
Mendeliome v1.5001 DENR Zornitza Stark Gene: denr has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5000 DENR Zornitza Stark gene: DENR was added
gene: DENR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DENR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DENR were set to 27239039
Phenotypes for gene: DENR were set to Neurodevelopmental disorder, MONDO:0700092, DENR-related
Review for gene: DENR was set to AMBER
Added comment: Two individuals from two unrelated families with de novo heterozygous missense variants in DENR presenting with a neurodevelopmental disorder characterised by autism, epilepsy and periventricular nodular heterotopia. Functional assays—including a mouse in utero electroporation rescue assay, Drosophila S2 cell stuORF reporter and HeLa stuORF reporter—demonstrate loss‑of‑function, satisfying the functional criteria for disease causality.

However, no further reports in 10 years -- hence Amber rating.
Sources: Literature
Hypogonadotropic hypogonadism v0.137 EMX2 Zornitza Stark Tag disputed was removed from gene: EMX2.
Callosome v0.595 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Differences of Sex Development v1.56 EMX2 Zornitza Stark Tag disputed was removed from gene: EMX2.
Intellectual disability syndromic and non-syndromic v1.825 MDGA2 Zornitza Stark Phenotypes for gene: MDGA2 were changed from MDGA2-related neurodevelopmental disorder MONDO:0700092 to Developmental and epileptic encephalopathy 122, MIM# 621608
Intellectual disability syndromic and non-syndromic v1.824 MDGA2 Zornitza Stark edited their review of gene: MDGA2: Changed phenotypes: Developmental and epileptic encephalopathy 122, MIM# 621608
Genetic Epilepsy v1.433 MDGA2 Zornitza Stark Phenotypes for gene: MDGA2 were changed from MDGA2-related neurodevelopmental disorder MONDO:0700092 to Developmental and epileptic encephalopathy 122, MIM# 621608
Genetic Epilepsy v1.432 MDGA2 Zornitza Stark reviewed gene: MDGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 122, MIM# 621608; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4999 MDGA2 Zornitza Stark Phenotypes for gene: MDGA2 were changed from MDGA2-related neurodevelopmental disorder MONDO:0700092 to Developmental and epileptic encephalopathy 122, MIM# 621608
Mendeliome v1.4998 MDGA2 Zornitza Stark reviewed gene: MDGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 122, MIM# 621608; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.65 TIA1 Bryony Thompson Tag digenic tag was added to gene: TIA1.
Intellectual disability syndromic and non-syndromic v1.824 Bryony Thompson Copied gene NCOR1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.824 NCOR1 Bryony Thompson gene: NCOR1 was added
gene: NCOR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NCOR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NCOR1 were set to 32034166; 31849593; 30664766; 30289594; 29483668
Phenotypes for gene: NCOR1 were set to complex neurodevelopmental disorder, MONDO:0100038
Genetic Epilepsy v1.432 Bryony Thompson Copied gene NCOR1 from panel Mendeliome
Genetic Epilepsy v1.432 NCOR1 Bryony Thompson gene: NCOR1 was added
gene: NCOR1 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NCOR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NCOR1 were set to 32034166; 31849593; 30664766; 30289594; 29483668
Phenotypes for gene: NCOR1 were set to complex neurodevelopmental disorder, MONDO:0100038
Autism v0.253 Bryony Thompson Copied gene NCOR1 from panel Mendeliome
Autism v0.253 NCOR1 Bryony Thompson gene: NCOR1 was added
gene: NCOR1 was added to Autism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NCOR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NCOR1 were set to 32034166; 31849593; 30664766; 30289594; 29483668
Phenotypes for gene: NCOR1 were set to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4998 NCOR1 Bryony Thompson Marked gene: NCOR1 as ready
Mendeliome v1.4998 NCOR1 Bryony Thompson Gene: ncor1 has been classified as Green List (High Evidence).
Mendeliome v1.4998 NCOR1 Bryony Thompson Classified gene: NCOR1 as Green List (high evidence)
Mendeliome v1.4998 NCOR1 Bryony Thompson Gene: ncor1 has been classified as Green List (High Evidence).
Mendeliome v1.4997 NCOR1 Bryony Thompson gene: NCOR1 was added
gene: NCOR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCOR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NCOR1 were set to 32034166; 31849593; 30664766; 30289594; 29483668
Phenotypes for gene: NCOR1 were set to complex neurodevelopmental disorder, MONDO:0100038
Review for gene: NCOR1 was set to GREEN
Added comment: Monallelic association is green and biallelic association is red
Four unrelated families described in PMID 30289594, PMID 30664766 and PMID 31849593 each harbour de novo loss‑of‑function NCOR1 variants (splice‑site or stop‑gain or CNV) presenting with neurodevelopmental abnormalities ranging from autism, intellectual disability and epilepsy to lethal anencephaly, supporting NCOR1 haploinsufficiency as a cause of a complex neurodevelopmental disorder. PMID 29483668 reports a single recessive case with intellectual disability, joint hyperlaxity and thin skin, with a missense variant that is too common to be associated with dominant disease and a 17p11.2p12 deletion which includes NCOR1. PMID 32034166 describes an isolated case of ketotic hypoglycaemia, but these phenotypes lack sufficient genetic or functional evidence for diagnostic classification.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v1.52 MT-TN Zornitza Stark Marked gene: MT-TN as ready
Rhabdomyolysis and Metabolic Myopathy v1.52 MT-TN Zornitza Stark Gene: mt-tn has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.52 MT-TN Zornitza Stark Phenotypes for gene: MT-TN were changed from Mitochondrial myopathy to mitochondrial disease MONDO:0044970, MT-TN related
Rhabdomyolysis and Metabolic Myopathy v1.51 MT-TN Zornitza Stark edited their review of gene: MT-TN: Changed phenotypes: mitochondrial disease MONDO:0044970, MT-TN related
Hereditary Neuropathy v1.199 MT-TN Zornitza Stark Marked gene: MT-TN as ready
Hereditary Neuropathy v1.199 MT-TN Zornitza Stark Gene: mt-tn has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.199 MT-TN Zornitza Stark Phenotypes for gene: MT-TN were changed from Mitochondrial myopathy to mitochondrial disease MONDO:0044970, MT-TN related
Hereditary Neuropathy v1.198 MT-TN Zornitza Stark edited their review of gene: MT-TN: Changed phenotypes: mitochondrial disease MONDO:0044970, MT-TN related
Mitochondrial disease v1.25 MT-TN Zornitza Stark Phenotypes for gene: MT-TN were changed from mitochondrial disease MONDO:0044970, MT-TN related to mitochondrial disease MONDO:0044970, MT-TN related
Mitochondrial disease v1.25 MT-TN Zornitza Stark Phenotypes for gene: MT-TN were changed from Mitochondrial myopathy to mitochondrial disease MONDO:0044970, MT-TN related
Mitochondrial disease v1.24 MT-TN Zornitza Stark edited their review of gene: MT-TN: Changed phenotypes: mitochondrial disease MONDO:0044970, MT-TN related
Rhabdomyolysis and Metabolic Myopathy v1.51 Zornitza Stark Copied gene MT-TN from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.51 MT-TN Zornitza Stark gene: MT-TN was added
gene: MT-TN was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
Mode of inheritance for gene gene: MT-TN was set to MITOCHONDRIAL
Phenotypes for gene: MT-TN were set to Mitochondrial myopathy
Hereditary Neuropathy v1.198 Zornitza Stark Copied gene MT-TN from panel Mitochondrial disease
Hereditary Neuropathy v1.198 MT-TN Zornitza Stark gene: MT-TN was added
gene: MT-TN was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
Mode of inheritance for gene gene: MT-TN was set to MITOCHONDRIAL
Phenotypes for gene: MT-TN were set to Mitochondrial myopathy
Mitochondrial disease v1.24 MT-TN Zornitza Stark commented on gene: MT-TN: DEFINITIVE by ClinGen.

A variant in MT-TN first reported in a 27 yo woman with a history of PEO since 9 months of age, myopathy, decreased deep tendon reflexes, and thin body habitus. Subsequent publications have shown a consistent phenotype including ptosis, PEO, myopathy, neuropathy, with or without ataxia, muscle biopsy with COX-negative and ragged red fibers, and often either a complex IV deficiency in muscle or combined OXPHOS defect. One patient has been reported with basal ganglia calcifications and seizures in addition to myopathy and faltering growth (PMID:16908752). Two patients have been reported with focal segmental glomerular sclerosis (FSGS), which is a renal manifestation of some primary mitochondrial diseases (PMIDs: 16908752, 23375258).
Genetic Epilepsy v1.431 RAPGEF2 Zornitza Stark Classified gene: RAPGEF2 as Red List (low evidence)
Genetic Epilepsy v1.431 RAPGEF2 Zornitza Stark Gene: rapgef2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.430 SAMD12 Zornitza Stark Classified gene: SAMD12 as Green List (high evidence)
Genetic Epilepsy v1.430 SAMD12 Zornitza Stark Gene: samd12 has been classified as Green List (High Evidence).
Proteinuria v0.242 NUP205 Zornitza Stark Publications for gene: NUP205 were set to 26878725
Proteinuria v0.241 NUP205 Zornitza Stark Classified gene: NUP205 as Amber List (moderate evidence)
Proteinuria v0.241 NUP205 Zornitza Stark Gene: nup205 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.823 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.823 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.429 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Genetic Epilepsy v1.429 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.428 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Genetic Epilepsy v1.428 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.428 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Genetic Epilepsy v1.428 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.822 Sarah Milton Added reviews for gene CACNA2D1 from panel Mendeliome
Genetic Epilepsy v1.427 Sarah Milton Added reviews for gene CACNA2D1 from panel Mendeliome
Mendeliome v1.4996 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Mendeliome v1.4996 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4995 CACNA2D1 Sarah Milton Classified gene: CACNA2D1 as Amber List (moderate evidence)
Mendeliome v1.4995 CACNA2D1 Sarah Milton Gene: cacna2d1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4994 CACNA2D1 Sarah Milton reviewed gene: CACNA2D1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35293990, 24133248, 28097321; Phenotypes: Developmental and epileptic encephalopathy 110 MIM#620149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v1.107 CDKL1 Zornitza Stark Marked gene: CDKL1 as ready
Aortopathy_Connective Tissue Disorders v1.107 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.107 CDKL1 Zornitza Stark Phenotypes for gene: CDKL1 were changed from Neurodevelopmental disorder, MONDO:0700092, CDKL1-related; Connective tissue disorder, MONDO:0003900, CDKL1-related to Connective tissue disorder, MONDO:0003900, CDKL1-related
Aortopathy_Connective Tissue Disorders v1.106 CDKL1 Zornitza Stark Deleted their comment
Aortopathy_Connective Tissue Disorders v1.106 Zornitza Stark Copied gene CDKL1 from panel Mendeliome
Aortopathy_Connective Tissue Disorders v1.106 CDKL1 Zornitza Stark gene: CDKL1 was added
gene: CDKL1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CDKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL1 were set to PMID: 40088891; 41056017
Phenotypes for gene: CDKL1 were set to Neurodevelopmental disorder, MONDO:0700092, CDKL1-related; Connective tissue disorder, MONDO:0003900, CDKL1-related
Mode of pathogenicity for gene: CDKL1 was set to Other
Mendeliome v1.4994 CDKL1 Zornitza Stark Phenotypes for gene: CDKL1 were changed from Neurodevelopmental disorder, MONDO:0700092, CDKL1-related to Neurodevelopmental disorder, MONDO:0700092, CDKL1-related; Connective tissue disorder, MONDO:0003900, CDKL1-related
Mendeliome v1.4993 CDKL1 Zornitza Stark Publications for gene: CDKL1 were set to PMID: 40088891
Mendeliome v1.4992 CDKL1 Zornitza Stark Classified gene: CDKL1 as Amber List (moderate evidence)
Mendeliome v1.4992 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4991 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Added comment: PMID 41056017 reports 6 individuals from 3 unrelated families with heterozygous CDKL1 missense variants (c.427T>C p.Cys143Arg, c.617C>T p.Ser206Leu, c.404C>T p.Thr135Met) causing a thoracic aortic aneurysm and dissection (TAAD) spectrum disorder with craniofacial, skeletal and connective‑tissue features. The study provides variant‑specific functional data – zebrafish knock‑down/CRISPR knockout causing aortic dilation and intersegmental‑vessel defects rescued by wild‑type CDKL1 RNA, and in‑vitro kinase assays showing markedly reduced activity – supporting a loss‑of‑function mechanism.

p.Ser206Leu is observed in gnomAD in 59 hets, and NP_004187.3:p.Thr135Met in 128 hets, hence Amber rating.; Changed rating: AMBER; Changed publications: 41056017; Changed phenotypes: Connective tissue disorder, MONDO:0003900, CDKL1-related
Red cell disorders v1.67 SLC14A1 Zornitza Stark Marked gene: SLC14A1 as ready
Red cell disorders v1.67 SLC14A1 Zornitza Stark Gene: slc14a1 has been classified as Green List (High Evidence).
Red cell disorders v1.67 Zornitza Stark Copied gene SLC14A1 from panel Mendeliome
Red cell disorders v1.67 SLC14A1 Zornitza Stark gene: SLC14A1 was added
gene: SLC14A1 was added to Red cell disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC14A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC14A1 were set to 28065763; 27834480; 37165957; 33539287
Phenotypes for gene: SLC14A1 were set to Familial haemolytic anaemia, MONDO:0003689, SLC14A1-related; [Blood group, Kidd], MIM#111000
Mendeliome v1.4991 SLC14A1 Zornitza Stark Phenotypes for gene: SLC14A1 were changed from [Blood group, Kidd], MIM#111000 to Familial haemolytic anaemia, MONDO:0003689, SLC14A1-related; [Blood group, Kidd], MIM#111000
Mendeliome v1.4990 SLC14A1 Zornitza Stark Publications for gene: SLC14A1 were set to 28065763; 27834480
Mendeliome v1.4989 SLC14A1 Zornitza Stark Mode of inheritance for gene: SLC14A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4988 SLC14A1 Zornitza Stark Classified gene: SLC14A1 as Green List (high evidence)
Mendeliome v1.4988 SLC14A1 Zornitza Stark Gene: slc14a1 has been classified as Green List (High Evidence).
Mendeliome v1.4987 SLC14A1 Zornitza Stark reviewed gene: SLC14A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165957, 33539287; Phenotypes: Familial haemolytic anaemia, MONDO:0003689, SLC14A1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.587 PLAT Zornitza Stark Marked gene: PLAT as ready
Fetal anomalies v1.587 PLAT Zornitza Stark Gene: plat has been classified as Green List (High Evidence).
Fetal anomalies v1.587 PLAT Zornitza Stark Phenotypes for gene: PLAT were changed from Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872 to Syndromic disease, MONDO:0002254, PLAT-related
Fetal anomalies v1.586 PLAT Zornitza Stark Tag disputed was removed from gene: PLAT.
Intellectual disability syndromic and non-syndromic v1.821 PLAT Zornitza Stark Marked gene: PLAT as ready
Intellectual disability syndromic and non-syndromic v1.821 PLAT Zornitza Stark Gene: plat has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.821 PLAT Zornitza Stark Tag disputed was removed from gene: PLAT.
Intellectual disability syndromic and non-syndromic v1.821 PLAT Zornitza Stark Phenotypes for gene: PLAT were changed from Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872 to Syndromic disease, MONDO:0002254, PLAT-related
Hydrocephalus_Ventriculomegaly v0.140 PLAT Zornitza Stark Marked gene: PLAT as ready
Hydrocephalus_Ventriculomegaly v0.140 PLAT Zornitza Stark Gene: plat has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.140 PLAT Zornitza Stark Phenotypes for gene: PLAT were changed from Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872 to Syndromic disease, MONDO:0002254, PLAT-related
Hydrocephalus_Ventriculomegaly v0.139 PLAT Zornitza Stark Tag disputed was removed from gene: PLAT.
Intellectual disability syndromic and non-syndromic v1.820 Zornitza Stark Copied gene PLAT from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.820 PLAT Zornitza Stark gene: PLAT was added
gene: PLAT was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,ClinGen,ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLAT were set to 39574431; 37808270; 27417437
Phenotypes for gene: PLAT were set to Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Hydrocephalus_Ventriculomegaly v0.139 Zornitza Stark Copied gene PLAT from panel Mendeliome
Hydrocephalus_Ventriculomegaly v0.139 PLAT Zornitza Stark gene: PLAT was added
gene: PLAT was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review Green,ClinGen,ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLAT were set to 39574431; 37808270; 27417437
Phenotypes for gene: PLAT were set to Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Fetal anomalies v1.586 Zornitza Stark Copied gene PLAT from panel Mendeliome
Fetal anomalies v1.586 PLAT Zornitza Stark gene: PLAT was added
gene: PLAT was added to Fetal anomalies. Sources: Expert Review Green,ClinGen,ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLAT were set to 39574431; 37808270; 27417437
Phenotypes for gene: PLAT were set to Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Mendeliome v1.4987 PLAT Zornitza Stark Phenotypes for gene: PLAT were changed from Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872 to Syndromic disease, MONDO:0002254, PLAT-related; Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Mendeliome v1.4986 PLAT Zornitza Stark Publications for gene: PLAT were set to
Mendeliome v1.4985 PLAT Zornitza Stark Mode of inheritance for gene: PLAT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4984 PLAT Zornitza Stark Classified gene: PLAT as Green List (high evidence)
Mendeliome v1.4984 PLAT Zornitza Stark Gene: plat has been classified as Green List (High Evidence).
Mendeliome v1.4983 PLAT Zornitza Stark changed review comment from: PMID 39574431 adds three unrelated consanguineous families with distinct homozygous loss‑of‑function PLAT variants causing obstructive hydrocephalus, Dandy‑Walker malformation and intellectual disability. PMID 27417437 remains the sole report of a recessive lethal syndrome (congenital hydranencephaly with diaphragmatic hernia). Functional assays across papers demonstrate loss of tPA activity (SPR binding, fibrin‑lysis, Western blot) and mouse knockout phenotypes.; to: PMID 39574431 adds three unrelated consanguineous families with distinct homozygous loss‑of‑function PLAT variants causing obstructive hydrocephalus, Dandy‑Walker malformation and intellectual disability. PMID 27417437 remains the sole report of a recessive lethal syndrome (congenital hydranencephaly with diaphragmatic hernia). Functional assays across papers demonstrate loss of tPA activity (SPR binding, fibrin‑lysis, Western blot) and mouse knockout phenotypes.

DISPUTED for thrombophilia association.
Mendeliome v1.4983 PLAT Zornitza Stark reviewed gene: PLAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 39574431, 37808270, 27417437; Phenotypes: Syndromic disease, MONDO:0002254, PLAT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.542 ARHGAP24 Zornitza Stark Marked gene: ARHGAP24 as ready
Congenital Heart Defect v0.542 ARHGAP24 Zornitza Stark Gene: arhgap24 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.542 ARHGAP24 Zornitza Stark Phenotypes for gene: ARHGAP24 were changed from FSGS, MONDO:0005363, ARHGAP24-related; Mitral valve prolapse, MONDO:0004910, ARHGAP24-related to Mitral valve prolapse, MONDO:0004910, ARHGAP24-related
Congenital Heart Defect v0.541 ARHGAP24 Zornitza Stark Deleted their comment
Congenital Heart Defect v0.541 Zornitza Stark Copied gene ARHGAP24 from panel Mendeliome
Congenital Heart Defect v0.541 ARHGAP24 Zornitza Stark gene: ARHGAP24 was added
gene: ARHGAP24 was added to Congenital Heart Defect. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARHGAP24 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP24 were set to 21911940; 39484266
Phenotypes for gene: ARHGAP24 were set to FSGS, MONDO:0005363, ARHGAP24-related; Mitral valve prolapse, MONDO:0004910, ARHGAP24-related
Mendeliome v1.4983 ARHGAP24 Zornitza Stark Phenotypes for gene: ARHGAP24 were changed from FSGS, MONDO:0005363, ARHGAP24-related to FSGS, MONDO:0005363, ARHGAP24-related; Mitral valve prolapse, MONDO:0004910, ARHGAP24-related
Mendeliome v1.4982 ARHGAP24 Zornitza Stark Publications for gene: ARHGAP24 were set to 21911940
Mendeliome v1.4981 ARHGAP24 Zornitza Stark edited their review of gene: ARHGAP24: Added comment: PMID 39484266 adds 5 unrelated families (11 affected individuals) with autosomal dominant ARHGAP24 variants causing isolated posterior mitral valve prolapse. Variant‑specific functional assays demonstrate reduced Rac1‑GAP activity, and zebrafish morpholino knockdown recapitulates valvular regurgitation.

4 of the variants are missense, one LoF. All are present in gnomAD, some at high frequencies (e.g. NP_001020787.2:p.Thr481Met is present in over 2,000 individuals).; Changed publications: 39484266; Changed phenotypes: Mitral valve prolapse, MONDO:0004910, ARHGAP24-related
Intellectual disability syndromic and non-syndromic v1.819 NLGN1 Zornitza Stark Phenotypes for gene: NLGN1 were changed from Intellectual disability; autism; no OMIM number yet to Neurodevelopmental disorder, MONDO:0700092; autism, susceptibility to, 20, MONDO:0030004
Intellectual disability syndromic and non-syndromic v1.818 NLGN1 Zornitza Stark Publications for gene: NLGN1 were set to PMID: 30460678
Intellectual disability syndromic and non-syndromic v1.817 NLGN1 Zornitza Stark Mode of inheritance for gene: NLGN1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.816 NLGN1 Zornitza Stark Classified gene: NLGN1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.816 NLGN1 Zornitza Stark Gene: nlgn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.815 Zornitza Stark Added reviews for gene NLGN1 from panel Mendeliome
Mendeliome v1.4981 NLGN1 Zornitza Stark Phenotypes for gene: NLGN1 were changed from intellectual disability; autism to Neurodevelopmental disorder, MONDO:0700092; autism, susceptibility to, 20, MONDO:0030004
Mendeliome v1.4980 NLGN1 Zornitza Stark Publications for gene: NLGN1 were set to 30460678
Mendeliome v1.4979 NLGN1 Zornitza Stark Mode of inheritance for gene: NLGN1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4978 NLGN1 Zornitza Stark Classified gene: NLGN1 as Amber List (moderate evidence)
Mendeliome v1.4978 NLGN1 Zornitza Stark Gene: nlgn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4977 NLGN1 Zornitza Stark edited their review of gene: NLGN1: Added comment: PMID 28841651 adds five unrelated families with heterozygous missense NLGN1 variants causing autism; functional assays demonstrate loss‑of‑function and a P89L knock‑in mouse recapitulates social deficits. PMID 38739110 adds two families (one de novo) with a neurodevelopmental disorder including intellectual disability, autism and epilepsy harbouring missense NLGN1 variants.

At least one of the variants reported has a relatively high population frequency, not consistent with a monogenic disorder (e.g. p.Thr90Ile with 162 hets).; Changed rating: AMBER; Changed publications: 38739110, 28841651; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, autism, susceptibility to, 20, MONDO:0030004; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v1.34 MC3R Zornitza Stark Marked gene: MC3R as ready
Severe early-onset obesity v1.34 MC3R Zornitza Stark Gene: mc3r has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v1.34 Zornitza Stark Copied gene MC3R from panel Mendeliome
Severe early-onset obesity v1.34 MC3R Zornitza Stark gene: MC3R was added
gene: MC3R was added to Severe early-onset obesity. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: MC3R was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MC3R were set to 39462520; 37820740; 37329217
Phenotypes for gene: MC3R were set to {Obesity, severe, susceptibility to, BMIQ9} 602025
Mendeliome v1.4977 MC3R Zornitza Stark Publications for gene: MC3R were set to
Mendeliome v1.4976 MC3R Zornitza Stark Classified gene: MC3R as Amber List (moderate evidence)
Mendeliome v1.4976 MC3R Zornitza Stark Gene: mc3r has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4975 MC3R Zornitza Stark edited their review of gene: MC3R: Added comment: PMID 39462520: single individual reported with rare missense variant (3 hets in gnomAD) and severe early onset obesity.

PMID 37820740: Reports six unrelated children (ages 7‑17, Chinese or Malay) with heterozygous MC3R missense variants causing severe early‑onset obesity (BMI ≥97th percentile). Four distinct variants (c.97G>A, c.127G>A, c.151G>C, c.437T>A) were identified; functional assays in HEK293 cells showed loss‑of‑function for c.127G>A and c.437T>A, while c.151G>C was neutral and c.97G>A modestly reduced signalling. All variants are present in gnomAD at low frequencies.

PMID 37329217: Reports 2 unrelated children each with a heterozygous missense MC3R variant associated with severe obesity. Variants are present in gnomAD at low frequencies.; Changed rating: AMBER; Changed publications: 39462520, 37820740, 37329217
Infertility and Recurrent Pregnancy Loss v1.176 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Infertility and Recurrent Pregnancy Loss v1.176 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v1.176 SOX8 Zornitza Stark Phenotypes for gene: SOX8 were changed from Neurodevelopmental disorder (MONDO:0700092), SOX8-related; Infertility disorder, MONDO:0005047, SOX8-related to Infertility disorder, MONDO:0005047, SOX8-related
Infertility and Recurrent Pregnancy Loss v1.175 SOX8 Zornitza Stark Mode of inheritance for gene: SOX8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.421 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.421 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.421 SOX8 Zornitza Stark Phenotypes for gene: SOX8 were changed from Neurodevelopmental disorder (MONDO:0700092), SOX8-related; Infertility disorder, MONDO:0005047, SOX8-related to Infertility disorder, MONDO:0005047, SOX8-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.420 SOX8 Zornitza Stark Mode of inheritance for gene: SOX8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.419 Zornitza Stark Copied gene SOX8 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.419 SOX8 Zornitza Stark gene: SOX8 was added
gene: SOX8 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SOX8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to 39595984; 38235364; 36631813; 35734438; 29373757
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related; Infertility disorder, MONDO:0005047, SOX8-related
Infertility and Recurrent Pregnancy Loss v1.174 Zornitza Stark Copied gene SOX8 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.174 SOX8 Zornitza Stark gene: SOX8 was added
gene: SOX8 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SOX8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to 39595984; 38235364; 36631813; 35734438; 29373757
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related; Infertility disorder, MONDO:0005047, SOX8-related
Mendeliome v1.4975 SOX8 Zornitza Stark Phenotypes for gene: SOX8 were changed from Neurodevelopmental disorder (MONDO:0700092), SOX8-related to Neurodevelopmental disorder (MONDO:0700092), SOX8-related; Infertility disorder, MONDO:0005047, SOX8-related
Mendeliome v1.4974 SOX8 Zornitza Stark Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Mendeliome v1.4973 SOX8 Zornitza Stark Mode of inheritance for gene: SOX8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4972 SOX8 Zornitza Stark reviewed gene: SOX8: Rating: RED; Mode of pathogenicity: None; Publications: 39595984, 38235364, 36631813, 35734438, 29373757; Phenotypes: Infertility disorder, MONDO:0005047, SOX8-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.88 MED12 Zornitza Stark Marked gene: MED12 as ready
Craniosynostosis v1.88 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.88 MED12 Zornitza Stark Classified gene: MED12 as Amber List (moderate evidence)
Craniosynostosis v1.88 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.87 MED12 Zornitza Stark gene: MED12 was added
gene: MED12 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MED12 were set to 19938245
Phenotypes for gene: MED12 were set to Opitz-Kaveggia (FG) syndrome, MIM#305450
Review for gene: MED12 was set to AMBER
Added comment: Craniosynostosis is a rare feature of this syndrome.
Sources: Literature
Severe early-onset obesity v1.33 APBA1 Zornitza Stark Marked gene: APBA1 as ready
Severe early-onset obesity v1.33 APBA1 Zornitza Stark Gene: apba1 has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v1.33 Zornitza Stark Copied gene APBA1 from panel Mendeliome
Severe early-onset obesity v1.33 APBA1 Zornitza Stark gene: APBA1 was added
gene: APBA1 was added to Severe early-onset obesity. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: APBA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APBA1 were set to 42018264
Phenotypes for gene: APBA1 were set to Obesity disorder, MONDO:0011122, APBA1-related
Mendeliome v1.4972 APBA1 Zornitza Stark Marked gene: APBA1 as ready
Mendeliome v1.4972 APBA1 Zornitza Stark Gene: apba1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4972 APBA1 Zornitza Stark Classified gene: APBA1 as Amber List (moderate evidence)
Mendeliome v1.4972 APBA1 Zornitza Stark Gene: apba1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.173 NUP205 Zornitza Stark Marked gene: NUP205 as ready
Infertility and Recurrent Pregnancy Loss v1.173 NUP205 Zornitza Stark Gene: nup205 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.173 NUP205 Zornitza Stark Phenotypes for gene: NUP205 were changed from Nephrotic syndrome, type 13, MIM#616893; Visceral heterotaxy MONDO:0018677; Premature ovarian failure, MONDO:0019852, NUP205-related to Premature ovarian failure, MONDO:0019852, NUP205-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.418 NUP205 Zornitza Stark Marked gene: NUP205 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.418 NUP205 Zornitza Stark Gene: nup205 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.418 NUP205 Zornitza Stark Phenotypes for gene: NUP205 were changed from Nephrotic syndrome, type 13, MIM#616893; Visceral heterotaxy MONDO:0018677; Premature ovarian failure, MONDO:0019852, NUP205-related to Premature ovarian failure, MONDO:0019852, NUP205-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.417 Zornitza Stark Copied gene NUP205 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.417 NUP205 Zornitza Stark gene: NUP205 was added
gene: NUP205 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NUP205 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NUP205 were set to 26878725; 31306055; 33065118; 36245711; 42049205
Phenotypes for gene: NUP205 were set to Nephrotic syndrome, type 13, MIM#616893; Visceral heterotaxy MONDO:0018677; Premature ovarian failure, MONDO:0019852, NUP205-related
Infertility and Recurrent Pregnancy Loss v1.172 Zornitza Stark Copied gene NUP205 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.172 NUP205 Zornitza Stark gene: NUP205 was added
gene: NUP205 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NUP205 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NUP205 were set to 26878725; 31306055; 33065118; 36245711; 42049205
Phenotypes for gene: NUP205 were set to Nephrotic syndrome, type 13, MIM#616893; Visceral heterotaxy MONDO:0018677; Premature ovarian failure, MONDO:0019852, NUP205-related
Mendeliome v1.4971 NUP205 Zornitza Stark Phenotypes for gene: NUP205 were changed from Nephrotic syndrome, type 13, MIM#616893 to Nephrotic syndrome, type 13, MIM#616893; Visceral heterotaxy MONDO:0018677; Premature ovarian failure, MONDO:0019852, NUP205-related
Mendeliome v1.4970 NUP205 Zornitza Stark Publications for gene: NUP205 were set to 26878725
Mendeliome v1.4969 NUP205 Zornitza Stark Mode of inheritance for gene: NUP205 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4968 NUP205 Zornitza Stark Classified gene: NUP205 as Green List (high evidence)
Mendeliome v1.4968 NUP205 Zornitza Stark Gene: nup205 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.454 GHRHR Zornitza Stark reviewed gene: GHRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Red cell disorders v1.66 RACGAP1 Zornitza Stark Classified gene: RACGAP1 as Green List (high evidence)
Red cell disorders v1.66 RACGAP1 Zornitza Stark Gene: racgap1 has been classified as Green List (High Evidence).
Red cell disorders v1.65 RACGAP1 Zornitza Stark edited their review of gene: RACGAP1: Added comment: PMID 36200420 Reports an additional 3 individuals from 3 families with autosomal recessive RACGAP1 missense variants presenting with congenital dyserythropoietic anemia type III (macrocytic anemia, multinucleated erythroblasts, hepatosplenomegaly). Variants are homozygous missense (p.Pro432Ser, p.Thr220Ala); functional studies in patient CD34+ erythroid cells and HeLa cells demonstrate rescue by wild‑type RACGAP1, supporting loss‑of‑function as a disease mechanism.; Changed rating: GREEN; Changed publications: 34818416, 36200420; Changed phenotypes: Anaemia, congenital dyserythropoietic, type IIIb, autosomal recessive 619789
Mendeliome v1.4967 RACGAP1 Zornitza Stark Publications for gene: RACGAP1 were set to 34818416
Mendeliome v1.4966 RACGAP1 Zornitza Stark Classified gene: RACGAP1 as Green List (high evidence)
Mendeliome v1.4966 RACGAP1 Zornitza Stark Gene: racgap1 has been classified as Green List (High Evidence).
Mendeliome v1.4965 RACGAP1 Rylee Peters changed review comment from: PMID 36200420The study adds three unrelated families with autosomal recessive congenital dyserythropoietic anemia type III caused by homozygous missense RACGAP1 variants (p.Pro432Ser and p.Thr220Ala, the latter present in two families). Variant‑specific functional rescue in patient CD34⁺ erythroid cells and orthogonal HeLa knock‑down/ rescue assays demonstrate a loss‑of‑function mechanism.

PMID 36200420 Reports an additional 3 individuals from 3 families with autosomal recessive RACGAP1 missense variants presenting with congenital dyserythropoietic anemia type III (macrocytic anemia, multinucleated erythroblasts, hepatosplenomegaly). Variants are homozygous missense (p.Pro432Ser, p.Thr220Ala); functional studies in patient CD34+ erythroid cells and HeLa cells demonstrate rescue by wild‑type RACGAP1, supporting loss‑of‑function as disease mechanism.; to: PMID 36200420 Reports an additional 3 individuals from 3 families with autosomal recessive RACGAP1 missense variants presenting with congenital dyserythropoietic anemia type III (macrocytic anemia, multinucleated erythroblasts, hepatosplenomegaly). Variants are homozygous missense (p.Pro432Ser, p.Thr220Ala); functional studies in patient CD34+ erythroid cells and HeLa cells demonstrate rescue by wild‑type RACGAP1, supporting loss‑of‑function as a disease mechanism.
Autoinflammatory Disorders v2.47 ADAM17 Zornitza Stark Publications for gene: ADAM17 were set to 22010916; 29560122; 26683521; 25804906
Autoinflammatory Disorders v2.46 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: PMID 34993966: single individual with biallelic loss‑of‑function ADAM17 variants (c.2082+2dupT and c.620-385_843+1015del) presenting with neonatal inflammatory skin and bowel disease type 1 (erythroderma, atrichia, nail dystrophy, oesophageal stricture, intractable diarrhoea, failure‑to‑thrive, recurrent infections). The splice variant causes exon 17 skipping; the deletion removes exons 6‑7. Skin improved with combined ustekinumab and certolizumab; intestinal disease responded to budesonide.

PMID 40968583 reports another individual with homozygous splice site variant presenting with neonatal inflammatory skin and bowel disease, chronic diarrhoea, failure to thrive, pustular rash, and recurrent bacterial infections.

PMID 42015567: reports single individual with a homozygous missense ADAM17 variant presenting with severe cutaneous inflammation, mucosal ulcerations, annular scarring, developmental delay and no bowel disease.; Changed publications: 22010916, 29560122, 26683521, 25804906, 34993966, 40968583, 42015567
Inflammatory bowel disease v0.127 ADAM17 Zornitza Stark Publications for gene: ADAM17 were set to 22010916; 29560122; 26683521; 25804906
Inflammatory bowel disease v0.126 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: PMID 34993966: single individual with biallelic loss‑of‑function ADAM17 variants (c.2082+2dupT and c.620-385_843+1015del) presenting with neonatal inflammatory skin and bowel disease type 1 (erythroderma, atrichia, nail dystrophy, oesophageal stricture, intractable diarrhoea, failure‑to‑thrive, recurrent infections). The splice variant causes exon 17 skipping; the deletion removes exons 6‑7. Skin improved with combined ustekinumab and certolizumab; intestinal disease responded to budesonide.

PMID 40968583 reports another individual with homozygous splice site variant presenting with neonatal inflammatory skin and bowel disease, chronic diarrhoea, failure to thrive, pustular rash, and recurrent bacterial infections.

PMID 42015567: reports single individual with a homozygous missense ADAM17 variant presenting with severe cutaneous inflammation, mucosal ulcerations, annular scarring, developmental delay and no bowel disease.; Changed publications: 22010916, 29560122, 26683521, 25804906, 34993966, 40968583, 42015567
Mendeliome v1.4965 ADAM17 Zornitza Stark Publications for gene: ADAM17 were set to 22010916; 25804906; 21041656; 22236242
Mendeliome v1.4964 ADAM17 Zornitza Stark Mode of inheritance for gene: ADAM17 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4963 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Changed phenotypes: Hypotrichosis 16, MIM# 621490, Inflammatory skin and bowel disease, neonatal, 1, MIM# 614328; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4963 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: PMID 34993966: single individual with biallelic loss‑of‑function ADAM17 variants (c.2082+2dupT and c.620-385_843+1015del) presenting with neonatal inflammatory skin and bowel disease type 1 (erythroderma, atrichia, nail dystrophy, oesophageal stricture, intractable diarrhoea, failure‑to‑thrive, recurrent infections). The splice variant causes exon 17 skipping; the deletion removes exons 6‑7. Skin improved with combined ustekinumab and certolizumab; intestinal disease responded to budesonide.; Changed publications: 38771644, 42015567, 40968583, 34993966
Mendeliome v1.4963 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: PMID 40968583 reports another individual with homozygous splice site variant presenting with neonatal inflammatory skin and bowel disease, chronic diarrhoea, failure to thrive, pustular rash, and recurrent bacterial infections.; Changed rating: GREEN; Changed publications: 38771644, 42015567, 40968583
Mendeliome v1.4963 ADAM17 Zornitza Stark edited their review of gene: ADAM17: Added comment: PMID 42015567: reports single individual with a homozygous missense ADAM17 variant presenting with severe cutaneous inflammation, mucosal ulcerations, annular scarring, developmental delay and no bowel disease.; Changed publications: 38771644, 42015567
Mendeliome v1.4963 JAK2 Zornitza Stark Phenotypes for gene: JAK2 were changed from Thrombocythaemia 3, MIM# 614521 to Thrombocythaemia 3, MIM# 614521; Familial polycythemia MONDO:0001115, JAK2-related
Mendeliome v1.4962 JAK2 Zornitza Stark Publications for gene: JAK2 were set to 22397670; 35129130; 41053421; 39657124; 39323414
Mendeliome v1.4961 JAK2 Zornitza Stark edited their review of gene: JAK2: Changed phenotypes: Thrombocythaemia 3, MIM# 614521, Familial polycythemia MONDO:0001115, JAK2-related
Mendeliome v1.4961 JAK2 Zornitza Stark changed review comment from: Association with thrombocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.; to: Association with erythrocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.
Mendeliome v1.4961 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: Association with thrombocytosis:

PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.

PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.; Changed publications: 22397670, 35129130, 41053421, 39657124, 39323414, 35764421, 38629639
Red cell disorders v1.65 JAK2 Zornitza Stark Phenotypes for gene: JAK2 were changed from Erythrocytosis, somatic, 133100 to Erythrocytosis, somatic, 133100; Familial polycythemia MONDO:0001115, JAK2-related
Red cell disorders v1.64 JAK2 Zornitza Stark Publications for gene: JAK2 were set to 27389715
Red cell disorders v1.63 JAK2 Zornitza Stark Mode of inheritance for gene: JAK2 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.62 JAK2 Zornitza Stark Classified gene: JAK2 as Green List (high evidence)
Red cell disorders v1.62 JAK2 Zornitza Stark Gene: jak2 has been classified as Green List (High Evidence).
Red cell disorders v1.61 JAK2 Zornitza Stark changed review comment from: PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated hemoglobin/hematocrit and no thrombosis.; to: PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated haemoglobin/haematocrit and no thrombosis.
Red cell disorders v1.61 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: PMID 35764421: Reports 3 individuals from a single family with heterozygous germline JAK2 p.E846D missense variants presenting with adult‑onset erythrocytosis, elevated hemoglobin/hematocrit and no thrombosis.; Changed rating: GREEN; Changed publications: 27389715, 38629639, 35764421
Red cell disorders v1.61 JAK2 Zornitza Stark edited their review of gene: JAK2: Changed phenotypes: Erythrocytosis, somatic, 133100, Familial polycythemia MONDO:0001115, JAK2-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Red cell disorders v1.61 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: PMID 38629639: Reports 3 individuals from a single family with a heterozygous germline JAK2 R715T missense gain‑of‑function variant presenting with PV‑like erythrocytosis (elevated Hb, low‑normal EPO, no thrombocytosis/leukocytosis). Detailed clinical data for proband, mother and son are provided, together with in‑vitro luciferase, Ba/F3‑EPOR proliferation, p‑STAT5 and EPO‑independent BFU‑E assays demonstrating increased JAK‑STAT signalling. Ropeg‑IFNα treatment induced remission in proband and mother.; Changed publications: 27389715, 38629639
Bleeding and Platelet Disorders v1.79 Zornitza Stark Copied gene JAK2 from panel Mendeliome
Bleeding and Platelet Disorders v1.79 JAK2 Zornitza Stark gene: JAK2 was added
gene: JAK2 was added to Bleeding and Platelet Disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
somatic tags were added to gene: JAK2.
Mode of inheritance for gene: JAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAK2 were set to 22397670; 35129130; 41053421; 39657124; 39323414
Phenotypes for gene: JAK2 were set to Thrombocythaemia 3, MIM# 614521
Mendeliome v1.4961 JAK2 Zornitza Stark Publications for gene: JAK2 were set to 22397670; 35129130
Mendeliome v1.4960 JAK2 Zornitza Stark Classified gene: JAK2 as Green List (high evidence)
Mendeliome v1.4960 JAK2 Zornitza Stark Gene: jak2 has been classified as Green List (High Evidence).
Mendeliome v1.4959 JAK2 Zornitza Stark edited their review of gene: JAK2: Added comment: PMID 41053421: three individuals with germline c.1691 G > A, p.Arg564Gln (R564Q) gain-of-function variant and thrombocytosis.
PMID 39657124: Reports 12 individuals from 10 families with heterozygous germline JAK2 p.R564Q/L variants presenting with hereditary thrombocythemia (HT) and variable predisposition to myeloproliferative neoplasms (ET, PV) and lymphoid malignancies (CLL, AML, MGUS).
PMID 39323414: Reports 8 individuals from a single family with heterozygous germline JAK2 F556V gain‑of‑function variants presenting with familial thrombocytosis (hereditary thrombocythemia).

Overall, sufficient cases with germline variants for GREEN rating.; Changed rating: GREEN; Changed publications: 22397670, 35129130, 41053421, 39657124, 39323414
Hydrocephalus_Ventriculomegaly v0.138 TCF12 Chirag Patel Publications for gene: TCF12 were set to 23354436
Hydrocephalus_Ventriculomegaly v0.138 TCF12 Chirag Patel Phenotypes for gene: TCF12 were changed from TCF12-related craniosynostosis, MONDO:0014128 to TCF12-related craniosynostosis, MONDO:0014128
Hydrocephalus_Ventriculomegaly v0.138 TCF12 Chirag Patel Classified gene: TCF12 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.138 TCF12 Chirag Patel Gene: tcf12 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.137 TCF12 Chirag Patel Classified gene: TCF12 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.137 TCF12 Chirag Patel Gene: tcf12 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.136 TCF12 Chirag Patel Phenotypes for gene: TCF12 were changed from to TCF12-related craniosynostosis, MONDO:0014128
Hydrocephalus_Ventriculomegaly v0.136 TCF12 Chirag Patel Publications for gene: TCF12 were set to
Hydrocephalus_Ventriculomegaly v0.136 TCF12 Chirag Patel Mode of inheritance for gene: TCF12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.136 TCF12 Chirag Patel Classified gene: TCF12 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.136 TCF12 Chirag Patel Gene: tcf12 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel Marked gene: TCF12 as ready
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel Gene: tcf12 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354436; Phenotypes: TCF12-related craniosynostosis, MONDO:0014128; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel Deleted their review
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel Classified gene: TCF12 as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v0.135 TCF12 Chirag Patel Gene: tcf12 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.134 TCF12 Chirag Patel reviewed gene: TCF12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v0.454 GHRHR Sangavi Sivagnanasundram Classified gene: GHRHR as Green List (high evidence)
Skeletal dysplasia v0.454 GHRHR Sangavi Sivagnanasundram Gene: ghrhr has been classified as Green List (High Evidence).
Skeletal dysplasia v0.453 GHRHR Sangavi Sivagnanasundram Classified gene: GHRHR as Red List (low evidence)
Skeletal dysplasia v0.453 GHRHR Sangavi Sivagnanasundram Gene: ghrhr has been classified as Red List (Low Evidence).
Mendeliome v1.4959 RACGAP1 Rylee Peters reviewed gene: RACGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36200420; Phenotypes: Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive, MONDO:0030711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.452 GHRHR Sangavi Sivagnanasundram gene: GHRHR was added
gene: GHRHR was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GHRHR were set to PMID: 10084571, 8391647, 24450934
Phenotypes for gene: GHRHR were set to isolated growth hormone deficiency type IB MONDO:0013006
Review for gene: GHRHR was set to GREEN
Added comment: Isolated growth hormone deficiency type IV (IGHD4) is characterised by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I and IGF-binding protein-3 concentrations, and a good response to growth hormone treatment.

Skeletal dysplasia/ delayed bone age is a feature of this condition.
Sources: Other
Skeletal dysplasia v0.451 PFN1 Zornitza Stark Marked gene: PFN1 as ready
Skeletal dysplasia v0.451 PFN1 Zornitza Stark Gene: pfn1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.451 PFN1 Zornitza Stark Classified gene: PFN1 as Amber List (moderate evidence)
Skeletal dysplasia v0.451 PFN1 Zornitza Stark Gene: pfn1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.450 PFN1 Zornitza Stark gene: PFN1 was added
gene: PFN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PFN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFN1 were set to 33599011; 32392277; 31991009; 31346562
Phenotypes for gene: PFN1 were set to Paget disease of bone 7, early-onset, MIM# 621600
Review for gene: PFN1 was set to AMBER
Added comment: Three multiplex families reported with same variant, c.318_321delTGAC, and Paget's disease of bone. Two are from the same region in Italy, whereas the third is Chinese, making a founder variant less likely. Functional studies of this truncating variant showed abnormal protein aggregates (PMID: 32392277, 31991009). An osteoclast-specific conditional null mouse model confirmed the skeletal phenotype (PMID: 31346562).
Sources: Literature
Mendeliome v1.4959 PFN1 Zornitza Stark Publications for gene: PFN1 were set to 23141414; 22801503; 25499087; 24309268; 22801503; 26908597; 32392277; 31991009; 31346562; 32589291; 31802421; 31611772; 31401564; 30203378; 28040732
Mendeliome v1.4958 PFN1 Zornitza Stark edited their review of gene: PFN1: Added comment: PMID 33599011 reports multiplex Chinese family with same variant, c.318_321delTGAC, making it less likely to be a founder variant. However, still a single variant reported, albeit in 3 families so association with Paget's disease may be variant-specific, hence evidence for this association still considered moderate (Amber).; Changed publications: 33599011, 31802421, 31611772, 31401564, 30203378, 28040732, 22801503
Mendeliome v1.4958 PFN1 Zornitza Stark Phenotypes for gene: PFN1 were changed from Amyotrophic lateral sclerosis 18 (MIM# 614808); Paget’s disease of bone to Amyotrophic lateral sclerosis 18 (MIM# 614808); Paget disease of bone 7, early-onset, MIM# 621600
Speech apraxia v1.40 NSD1 Hali Van Niel gene: NSD1 was added
gene: NSD1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD1 were set to 41530369; 16001444
Phenotypes for gene: NSD1 were set to Sotos syndrome (MIM#117550)
Review for gene: NSD1 was set to RED
Added comment: Reported individual with CAS and de novo in frame deletion (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

While speech delay or impairment is prevalent in Sotos syndrome, Ball et al. (2005; PMID: 16001444) found errors appear to be language-related rather than motoric and therefore this is not enough to promote evidence.
Sources: Expert List, Literature
Speech apraxia v1.40 KCND3 Hali Van Niel gene: KCND3 was added
gene: KCND3 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCND3 were set to 41530369; 32823520; 23280838; 34361012
Phenotypes for gene: KCND3 were set to Spinocerebellar ataxia 19 (MIM#607346)
Review for gene: KCND3 was set to GREEN
Added comment: Reported individual with CAS and de novo missense variant (c.983 T > G; p.(Leu328Arg)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

Spinocerebellar ataxia clinically characterised by dysarthria, and over 20 reported cases with dysarthria (motor speech disorder) (PMID: 32823520)

Loss of function and gain of function are known mechanisms of disease in this gene. Missense variants have been reported to cause both a loss of function and gain of function effect (PMID: 23280838, PMID:34361012)
Sources: Expert List, Literature
Speech apraxia v1.40 FBXW7 Hali Van Niel gene: FBXW7 was added
gene: FBXW7 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to 41530369; 35395208
Phenotypes for gene: FBXW7 were set to Developmental delay, hypotonia, and impaired language (MIM#620012)
Review for gene: FBXW7 was set to RED
Added comment: Reported individual with CAS and frameshift variant (c.1919delG; p.(Ser640Thrfs*7)) (Van Niel et al., 2026; PMID: 41530369) leading to truncated protein. Validated diagnostic finding from VCGS clinical NATA pipeline

FBXW7 variants associated with variable neurodevelopmental condition, including impaired speech (PMID: 35395208)
Sources: Expert List, Literature
Speech apraxia v1.40 CUX1 Hali Van Niel gene: CUX1 was added
gene: CUX1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUX1 were set to 41530369; PMID: 37644171
Phenotypes for gene: CUX1 were set to Neurodevelopmental disorder with developmental delay and with or without motor or speech delay (MIM#618330)
Review for gene: CUX1 was set to RED
Added comment: Reported individual with CAS and de novo CUX1 intragenic deletion (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

Oppermann et al. (2023; PMID: 37644171) decribe 31 and 24 out of 32 individuals with CUX1 variants presented with speech and motor delay, respectively.
Sources: Expert List, Literature
Speech apraxia v1.40 CAMK2A Hali Van Niel gene: CAMK2A was added
gene: CAMK2A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CAMK2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2A were set to 41530369; 28130356; 29784083; 29560374
Phenotypes for gene: CAMK2A were set to Intellectual disability 53 (MIM#617798).
Mode of pathogenicity for gene: CAMK2A was set to Other
Review for gene: CAMK2A was set to RED
Added comment: Reported individual with CAS and dysarthria and de novo CAMK2A variant (c.635C>T; p.(Pro212Leu)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Dominant negative, loss of function and gain of function are known mechanisms of disease in
this gene and are associated with CAMK2A -related intellectual disability (PMID: 28130356, 29784083, 29560374)
Sources: Expert List, Literature
Speech apraxia v1.40 BPTF Hali Van Niel reviewed gene: BPTF: Rating: RED; Mode of pathogenicity: None; Publications: 41530369, 3352209; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MIM#617755); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v1.40 ANK2 Hali Van Niel reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: 41530369; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ANK2-related.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v1.40 ADGRL1 Hali Van Niel gene: ADGRL1 was added
gene: ADGRL1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to 41530369; 35907405
Phenotypes for gene: ADGRL1 were set to developmental delay, behavioural abnormalities, and neuropsychiatric disorders (MIM#620065).
Review for gene: ADGRL1 was set to RED
Added comment: Reported individual with CAS and maternal LoF variant (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic C4 finding from VCGS clinical NATA pipeline.

Vitobello et al. (2022; PMID: 35907405) report 9 unrelated individuals with ADGRL1 variants, 9/9 with unspecified speech delay.
Sources: Expert List, Literature
Genetic Epilepsy v1.426 RING1 Zornitza Stark Marked gene: RING1 as ready
Genetic Epilepsy v1.426 RING1 Zornitza Stark Gene: ring1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.426 RING1 Zornitza Stark Phenotypes for gene: RING1 were changed from complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038, RING1-related
Infertility and Recurrent Pregnancy Loss v1.171 ZAR1 Zornitza Stark Marked gene: ZAR1 as ready
Infertility and Recurrent Pregnancy Loss v1.171 ZAR1 Zornitza Stark Gene: zar1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.171 ZAR1 Zornitza Stark Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.416 ZAR1 Zornitza Stark Marked gene: ZAR1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.416 ZAR1 Zornitza Stark Gene: zar1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.416 ZAR1 Zornitza Stark Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.415 Zornitza Stark Copied gene ZAR1 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.415 ZAR1 Zornitza Stark gene: ZAR1 was added
gene: ZAR1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: ZAR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046
Phenotypes for gene: ZAR1 were set to Premature Ovarian Insufficiency MONDO:0005387, ZAR1-related; Multi locus imprinting disturbance in offspring
Infertility and Recurrent Pregnancy Loss v1.170 Zornitza Stark Copied gene ZAR1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.170 ZAR1 Zornitza Stark gene: ZAR1 was added
gene: ZAR1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: ZAR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046
Phenotypes for gene: ZAR1 were set to Premature Ovarian Insufficiency MONDO:0005387, ZAR1-related; Multi locus imprinting disturbance in offspring
Mendeliome v1.4957 ZAR1 Zornitza Stark Phenotypes for gene: ZAR1 were changed from Multi locus imprinting disturbance in offspring to Premature Ovarian Insufficiency MONDO:0005387, ZAR1-related; Multi locus imprinting disturbance in offspring
Mendeliome v1.4956 ZAR1 Zornitza Stark Mode of inheritance for gene: ZAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4955 ZAR1 Zornitza Stark Classified gene: ZAR1 as Green List (high evidence)
Mendeliome v1.4955 ZAR1 Zornitza Stark Gene: zar1 has been classified as Green List (High Evidence).
Mendeliome v1.4954 TSGA10 Zornitza Stark Marked gene: TSGA10 as ready
Mendeliome v1.4954 TSGA10 Zornitza Stark Gene: tsga10 has been classified as Green List (High Evidence).
Mendeliome v1.4954 TSGA10 Zornitza Stark Publications for gene: TSGA10 were set to 28905369
Infertility and Recurrent Pregnancy Loss v1.169 TSGA10 Zornitza Stark Marked gene: TSGA10 as ready
Infertility and Recurrent Pregnancy Loss v1.169 TSGA10 Zornitza Stark Gene: tsga10 has been classified as Green List (High Evidence).
Hereditary Pigmentary Disorders v1.7 STK11 Zornitza Stark Marked gene: STK11 as ready
Hereditary Pigmentary Disorders v1.7 STK11 Zornitza Stark Gene: stk11 has been classified as Green List (High Evidence).
Mendeliome v1.4953 FAT3 Zornitza Stark Marked gene: FAT3 as ready
Mendeliome v1.4953 FAT3 Zornitza Stark Gene: fat3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v1.197 FAT3 Zornitza Stark Marked gene: FAT3 as ready
Hereditary Neuropathy v1.197 FAT3 Zornitza Stark Gene: fat3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4953 MACF1 Zornitza Stark Phenotypes for gene: MACF1 were changed from Lissencephaly 9 with complex brainstem malformation, MIM# 618325; Congenital myasthenic syndrome, MONDO:0018940, MACF1-related to Neurodevelopmental disorder (MONDO:0700092), MACF1-related; Lissencephaly 9 with complex brainstem malformation, MIM# 618325; Congenital myasthenic syndrome, MONDO:0018940, MACF1-related
Mendeliome v1.4952 MACF1 Zornitza Stark Publications for gene: MACF1 were set to 30471716; 37721175; 30842214
Rasopathy v0.114 RRAS Zornitza Stark commented on gene: RRAS: Additional reports reviewed: one further de novo variant in PMID 34935735; evidence concerns regarding the other two reports, therefore maintain Amber rating.
Cardiomyopathy_Paediatric v0.234 NRAP Zornitza Stark Phenotypes for gene: NRAP were changed from Dilated cardiomyopathy to Cardiomopathy, dilated, 2N, MIM# 621595
Cardiomyopathy_Paediatric v0.233 NRAP Zornitza Stark edited their review of gene: NRAP: Changed phenotypes: Cardiomopathy, dilated, 2N, MIM# 621595
Mendeliome v1.4951 NRAP Zornitza Stark Phenotypes for gene: NRAP were changed from Dilated cardiomyopathy to Cardiomopathy, dilated, 2N, MIM# 621595
Mendeliome v1.4950 NRAP Zornitza Stark edited their review of gene: NRAP: Changed phenotypes: Cardiomopathy, dilated, 2N, MIM# 621595
Mendeliome v1.4950 TSHZ1 Rylee Peters Classified gene: TSHZ1 as Amber List (moderate evidence)
Mendeliome v1.4950 TSHZ1 Rylee Peters Gene: tshz1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4949 TSHZ1 Rylee Peters changed review comment from: Classified as LIMITED by ClinGen Syndromic Disorders GCEP on June 19, 2020. It was reevaluated on July 23, 2024 - still LIMITED.; to: Classified as LIMITED by ClinGen Syndromic Disorders GCEP on June 19, 2020. It was reevaluated on July 23, 2024 - still LIMITED.
Mendeliome v1.4949 TSHZ1 Rylee Peters reviewed gene: TSHZ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aural atresia, congenital, MIM# 607842; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4949 MACF1 Lucy Spencer changed review comment from: Biallelic neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense in the early NMD-escape region. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Monoallelic neurodevelopmental disorder GREEN:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder, including developmental delay/I in all and and epilepsy or macro/microcephaly in some. All variants are absent from gnomad. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.

The overlapping phenotype of the mono and biallelic neurodevelopmental disorders may be due to hypomorphic variants causing the biallelic disease, or there may be a correlation to do with the different isoforms of this gene or the location of the variants within the protein. Still a bit of uncertainty around these phenotypes due to the non-specific and variable phenotypes and limited functional validation but enough reports to call them green at this stage

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.; to: Biallelic neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense in the early NMD-escape region. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Monoallelic neurodevelopmental disorder GREEN:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder, including developmental delay in all and epilepsy or macro/microcephaly in some. All variants are absent from gnomad. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.

The overlapping phenotype of the mono and biallelic neurodevelopmental disorders may be due to hypomorphic variants causing the biallelic disease, or there may be a correlation to do with the different isoforms of this gene or the location of the variants within the protein. Still a bit of uncertainty around these phenotypes due to the non-specific and variable phenotypes and limited functional validation but enough reports to call them green at this stage

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.
Intellectual disability syndromic and non-syndromic v1.814 FEM1C Zornitza Stark Classified gene: FEM1C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.814 FEM1C Zornitza Stark Gene: fem1c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.813 FEM1C Zornitza Stark reviewed gene: FEM1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, FEM1C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4949 FEM1C Zornitza Stark Classified gene: FEM1C as Amber List (moderate evidence)
Mendeliome v1.4949 FEM1C Zornitza Stark Gene: fem1c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4948 FEM1C Zornitza Stark reviewed gene: FEM1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, FEM1C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.228 IRS4 Chirag Patel commented on gene: IRS4
Pituitary hormone deficiency v0.228 IRS4 Chirag Patel Marked gene: IRS4 as ready
Pituitary hormone deficiency v0.228 IRS4 Chirag Patel Gene: irs4 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.228 Chirag Patel Copied gene IRS4 from panel Congenital hypothyroidism
Pituitary hormone deficiency v0.228 IRS4 Chirag Patel gene: IRS4 was added
gene: IRS4 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRS4 were set to 30061370; 10644546
Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035
Intellectual disability syndromic and non-syndromic v1.813 MACF1 Lucy Spencer Mode of pathogenicity for gene: MACF1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Intellectual disability syndromic and non-syndromic v1.812 MACF1 Lucy Spencer Publications for gene: MACF1 were set to 30471716
Hereditary Neuropathy v1.197 Lucy Spencer Copied gene FAT3 from panel Mendeliome
Hereditary Neuropathy v1.197 FAT3 Lucy Spencer gene: FAT3 was added
gene: FAT3 was added to Hereditary Neuropathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT3 were set to 41937739; 35853984; 31486992; 26559152
Phenotypes for gene: FAT3 were set to Peripheral neuropathy MONDO:0005244, FAT3-related
Mendeliome v1.4948 FAT3 Lucy Spencer Classified gene: FAT3 as Amber List (moderate evidence)
Mendeliome v1.4948 FAT3 Lucy Spencer Gene: fat3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4947 FAT3 Lucy Spencer gene: FAT3 was added
gene: FAT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT3 were set to 41937739; 35853984; 31486992; 26559152
Phenotypes for gene: FAT3 were set to Peripheral neuropathy MONDO:0005244, FAT3-related
Review for gene: FAT3 was set to AMBER
Added comment: AMBER for peripheral neuropathy PMID: 41937739 3 probands with peripheral neuropathies: distal muscle weakness, cranial nerve involvement, dysarthria, and bulbar involvement or respiratory failure. 2 probands had early childhood onset while the third had onset in their 30's. One proband was more severely affected with developmental abnormalities including congenital scoliosis, intestinal obstruction, ventriculomegaly, and corpus callosum thinning. All had homozygous or compound heterozygous missense (p.(Pro2041His, Cys3776Tyr, Met1749Val, Arg3276Gln), all fairly rare in gnomad with no homs. A neuron-specific knockdown of FAT3 in flies impaired motility, reduced lifespan and reduced synaptic branch length. intercrosses of mice heterozygous for the patient variant Pro2041His showed markedly fewer homozygotes than expected suggesting it is lethal in the homozygous state. KO mice and mice with Pro2041His exhibited CNS abnormalities including cerebellar abnormalities. Wide phenotypic variability and age of onset, only missense reported with functional studies only performed on one variant.

RED for Hirschprung PMID: 26559152 6 FAT3 variant across 5 families with Hirscprung disease. However 3 of the variants are common in gnomad (77 hets or more, 2 with homs). The paper also mentions non-segregation of the phenotype with the variant within some of these families.

RED for hyperparathyroidism PMID: 31486992 3 families with hyperparathyroidism and heterozygous missense variants in FAT3. 2 of the variants did not segregate well (observed in unaffected adult family members and/or not observed in affected family members). 2 of the variants were also very common in gnomad including homozygotes.

Red for isolated scoliosis PMID: 35853984 2 compound heterozygous missense in 3 siblings with adolescent scoliosis. the variants were common in gnomad with homozygotes.
Sources: Literature
Mendeliome v1.4946 MACF1 Lucy Spencer changed review comment from: Biallelic neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense in the early NMD-escape region. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Monoallelic neurodevelopmental disorder GREEN:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder, all are absent from gnomad. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.

The overlapping phenotype of the mono and biallelic neurodevelopmental disorders may be due to hypomorphic variants causing the biallelic disease, or there may be a correlation to do with the different isoforms of this gene or the location of the variants within the protein. Still a bit of uncertainty around these phenotypes due to the non-specific and variable phenotypes but enough reports to call them green at this stage

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.; to: Biallelic neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense in the early NMD-escape region. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Monoallelic neurodevelopmental disorder GREEN:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder, including developmental delay/I in all and and epilepsy or macro/microcephaly in some. All variants are absent from gnomad. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.

The overlapping phenotype of the mono and biallelic neurodevelopmental disorders may be due to hypomorphic variants causing the biallelic disease, or there may be a correlation to do with the different isoforms of this gene or the location of the variants within the protein. Still a bit of uncertainty around these phenotypes due to the non-specific and variable phenotypes and limited functional validation but enough reports to call them green at this stage

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.
Hereditary Pigmentary Disorders v1.7 STK11 Sangavi Sivagnanasundram Classified gene: STK11 as Green List (high evidence)
Hereditary Pigmentary Disorders v1.7 STK11 Sangavi Sivagnanasundram Gene: stk11 has been classified as Green List (High Evidence).
Hereditary Pigmentary Disorders v1.6 STK11 Sangavi Sivagnanasundram gene: STK11 was added
gene: STK11 was added to Hereditary Pigmentary Disorders. Sources: Expert Review
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STK11 were set to 15121768; 739570
Phenotypes for gene: STK11 were set to Peutz-Jeghers syndrome MONDO:0008280
Review for gene: STK11 was set to GREEN
Added comment: PJS is characterised by the development of gastrointestinal PJS-type hamartomatous polyps and mucocutaneous hyperpigmentation, which most often presents in childhood and fades by puberty.

Classified as DEFINITIVE by ClinGen Hereditary Cancer GCEP on 20/12/2023 - https://search.clinicalgenome.org/CCID:006288
Sources: Expert Review
Mendeliome v1.4946 MACF1 Lucy Spencer changed review comment from: Biallelic disease

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.

Neurodevelopmental disorder GREEN/AMBER:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Mostly missense reported with no functional, not a specific or very consistent phenotype.

Monoallelic:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. But 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex. ; to: Biallelic neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense in the early NMD-escape region. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Monoallelic neurodevelopmental disorder GREEN:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder, all are absent from gnomad. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.

The overlapping phenotype of the mono and biallelic neurodevelopmental disorders may be due to hypomorphic variants causing the biallelic disease, or there may be a correlation to do with the different isoforms of this gene or the location of the variants within the protein. Still a bit of uncertainty around these phenotypes due to the non-specific and variable phenotypes but enough reports to call them green at this stage

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.
Infertility and Recurrent Pregnancy Loss v1.169 TSGA10 Lucy Spencer Phenotypes for gene: TSGA10 were changed from spermatogenic failure MONDO:0004983 to Male infertility due to acephalic spermatozoa MONDO:0035153, TSGA10-related
Infertility and Recurrent Pregnancy Loss v1.168 TSGA10 Lucy Spencer Publications for gene: TSGA10 were set to 28905369
Infertility and Recurrent Pregnancy Loss v1.167 TSGA10 Lucy Spencer Classified gene: TSGA10 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.167 TSGA10 Lucy Spencer Gene: tsga10 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.166 Lucy Spencer Added reviews for gene TSGA10 from panel Mendeliome
Mendeliome v1.4946 TSGA10 Lucy Spencer Phenotypes for gene: TSGA10 were changed from spermatogenic failure MONDO:0004983 to Male infertility due to acephalic spermatozoa MONDO:0035153, TSGA10-related
Mendeliome v1.4945 TSGA10 Lucy Spencer Classified gene: TSGA10 as Green List (high evidence)
Mendeliome v1.4945 TSGA10 Lucy Spencer Gene: tsga10 has been classified as Green List (High Evidence).
Mendeliome v1.4944 TSGA10 Lucy Spencer reviewed gene: TSGA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 28905369, 32410354, 34409526, 34089195, 38317066, 32285443; Phenotypes: Male infertility due to acephalic spermatozoa MONDO:0035153, TSGA10-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v1.12 Sangavi Sivagnanasundram Added reviews for gene ZAR1 from panel Mendeliome
Mendeliome v1.4944 ZAR1 Sangavi Sivagnanasundram reviewed gene: ZAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36732629, 35296332; Phenotypes: Multi locus imprinting disturbance in offspring, Premature Ovarian Insufficiency MONDO:0005387, ZAR1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.425 RING1 Sangavi Sivagnanasundram Phenotypes for gene: RING1 were changed from microcephaly; intellectual disability to complex neurodevelopmental disorder, MONDO:0100038
Genetic Epilepsy v1.424 RING1 Sangavi Sivagnanasundram Publications for gene: RING1 were set to 29386386
Genetic Epilepsy v1.423 RING1 Sangavi Sivagnanasundram Mode of inheritance for gene: RING1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.422 RING1 Sangavi Sivagnanasundram Classified gene: RING1 as Green List (high evidence)
Genetic Epilepsy v1.422 RING1 Sangavi Sivagnanasundram Gene: ring1 has been classified as Green List (High Evidence).
Mendeliome v1.4944 RING1 Sangavi Sivagnanasundram Phenotypes for gene: RING1 were changed from microcephaly; intellectual disability to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4943 RING1 Sangavi Sivagnanasundram Publications for gene: RING1 were set to 29386386
Mendeliome v1.4942 RING1 Sangavi Sivagnanasundram Classified gene: RING1 as Green List (high evidence)
Mendeliome v1.4942 RING1 Sangavi Sivagnanasundram Gene: ring1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.811 RING1 Sangavi Sivagnanasundram Publications for gene: RING1 were set to 29386386; 41653922
Intellectual disability syndromic and non-syndromic v1.811 RING1 Sangavi Sivagnanasundram Publications for gene: RING1 were set to 29386386
Intellectual disability syndromic and non-syndromic v1.810 RING1 Sangavi Sivagnanasundram Phenotypes for gene: RING1 were changed from microcephaly; intellectual disability to complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability syndromic and non-syndromic v1.810 RING1 Sangavi Sivagnanasundram Classified gene: RING1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.810 RING1 Sangavi Sivagnanasundram Gene: ring1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.809 RING1 Sangavi Sivagnanasundram Classified gene: RING1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.809 RING1 Sangavi Sivagnanasundram Gene: ring1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.808 Sangavi Sivagnanasundram Added reviews for gene RING1 from panel Mendeliome
Genetic Epilepsy v1.421 Sangavi Sivagnanasundram Copied gene RING1 from panel Mendeliome
Genetic Epilepsy v1.421 RING1 Sangavi Sivagnanasundram gene: RING1 was added
gene: RING1 was added to Genetic Epilepsy. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RING1 were set to 29386386
Phenotypes for gene: RING1 were set to microcephaly; intellectual disability
Mendeliome v1.4941 RING1 Sangavi Sivagnanasundram reviewed gene: RING1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41653922; Phenotypes: complex neurodevelopmental disorder, MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and Metabolic Myopathy v1.50 MYH1 Lucy Spencer Publications for gene: MYH1 were set to 33755318
Rhabdomyolysis and Metabolic Myopathy v1.49 MYH1 Lucy Spencer Phenotypes for gene: MYH1 were changed from rhabdomyolysis, MONDO:0005290 to rhabdomyolysis, susceptibility to MONDO:0979250, MYH1-related
Rhabdomyolysis and Metabolic Myopathy v1.48 MYH1 Lucy Spencer Classified gene: MYH1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v1.48 MYH1 Lucy Spencer Gene: myh1 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.368 MYH1 Lucy Spencer Phenotypes for gene: MYH1 were changed from Hearing loss, autosomal recessive MONDO:0019588, MYH1-related; rhabdomyolysis, susceptibility to MONDO:0979250, MYH1-related to Hearing loss, autosomal recessive MONDO:0019588
Rhabdomyolysis and Metabolic Myopathy v1.47 Lucy Spencer Added reviews for gene MYH1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.367 Lucy Spencer Copied gene MYH1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.367 MYH1 Lucy Spencer gene: MYH1 was added
gene: MYH1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: MYH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYH1 were set to 33755318; 39482536; 39687948; 28074849; 32848021
Phenotypes for gene: MYH1 were set to Hearing loss, autosomal recessive MONDO:0019588, MYH1-related; rhabdomyolysis, susceptibility to MONDO:0979250, MYH1-related
Penetrance for gene: MYH1 were set to unknown
Mendeliome v1.4941 MYH1 Lucy Spencer edited their review of gene: MYH1: Changed publications: 33755318, 39482536, 39687948, 28074849, 32848021
Mendeliome v1.4941 MYH1 Lucy Spencer Phenotypes for gene: MYH1 were changed from rhabdomyolysis, MONDO:0005290 to Hearing loss, autosomal recessive MONDO:0019588, MYH1-related; rhabdomyolysis, susceptibility to MONDO:0979250, MYH1-related
Mendeliome v1.4940 MYH1 Lucy Spencer Publications for gene: MYH1 were set to 33755318
Mendeliome v1.4939 MYH1 Lucy Spencer Classified gene: MYH1 as Green List (high evidence)
Mendeliome v1.4939 MYH1 Lucy Spencer Gene: myh1 has been classified as Green List (High Evidence).
Mendeliome v1.4938 MYH1 Lucy Spencer reviewed gene: MYH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39482536, 33755318, 28074849, 32848021; Phenotypes: Hearing loss, autosomal recessive MONDO:0019588, MYH1-related, rhabdomyolysis, susceptibility to MONDO:0979250, MYH1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4938 NUP205 Rylee Peters reviewed gene: NUP205: Rating: GREEN; Mode of pathogenicity: None; Publications: 42049205; Phenotypes: Premature ovarian failure, MONDO:0019852, NUP205-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.585 MAB21L1 Zornitza Stark Phenotypes for gene: MAB21L1 were changed from Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479 to Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479; Microphthalmia MONDO:0021129, MAB21L1-related
Fetal anomalies v1.584 MAB21L1 Zornitza Stark Publications for gene: MAB21L1 were set to 30487245
Fetal anomalies v1.583 MAB21L1 Zornitza Stark Mode of inheritance for gene: MAB21L1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.582 MAB21L1 Zornitza Stark edited their review of gene: MAB21L1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.582 MAB21L1 Zornitza Stark edited their review of gene: MAB21L1: Added comment: PMID:33973683 (2021) reported a heterozygous novel variant in MAB21L1 gene (c.152G>T/ p.Arg51Leu), in two family members with microphthalmia and aniridia, as well as novel or rare compound heterozygous variants of uncertain significance (c.184C>T/ p.Arg62Cys; c.-68T>C and c.658G>C/ p.Gly220Arg; c.*529A>G) in two additional probands with microphthalmia, coloboma and/or cataracts. There is also function evidence available from in vitro studies of coding variants and in vivo complementation assays using the zebrafish mab21l2 Q48Sfs*5 loss-of-function line.

PMID:36413568 (2022) reported nine patients from five families with severe aniridia and/or microphthalmia with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. The detected variants are c.152G>A/ p.Arg51Gln, c.152G>T/ p.Arg51Leu, c.152G>C/ p.Arg51Pro and c.155T>G/ p.Phe52Cys. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes.

PMID:36446583 (2023) reported the identification of a novel missense variant (p.Phe52Leu) in a three-generation pedigree with autosomal dominant microphthalmia.

PMID:36892533 (2023) reported the identification of three heterozygous missense variants in MAB21L1 gene in five unrelated families, including c.152G>T/ p.Arg51Leu in two, c.152G>A/ p.Arg51Gln in two, and c.155T>G/ p.Phe52Cys in one. All patients presented with similar blepharophimosis plus anterior segment and macular dysgenesis (BAMD) phenotype.

PMID:39016008 (2024) reported an additional family with four individuals diagnosed with microphthalmia and with Arg51 variant in MAB21L1 gene.; Changed publications: 30487245, 39016008, 36892533, 36446583, 36413568; Changed phenotypes: Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479, Microphthalmia MONDO:0021129, MAB21L1-related
Fetal anomalies v1.582 Zornitza Stark Added reviews for gene MAB21L1 from panel Mendeliome
Mendeliome v1.4938 MAB21L1 Zornitza Stark Phenotypes for gene: MAB21L1 were changed from Cerebellar, ocular, craniofacial, and genital syndrome #MIM 618479 to Cerebellar, ocular, craniofacial, and genital syndrome #MIM 618479; Microphthalmia MONDO:0021129, MAB21L1-related
Mendeliome v1.4937 MAB21L1 Zornitza Stark Publications for gene: MAB21L1 were set to 30487245
Mendeliome v1.4936 MAB21L1 Zornitza Stark Mode of inheritance for gene: MAB21L1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4935 MAB21L1 Zornitza Stark reviewed gene: MAB21L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39016008, 36892533, 36446583, 36413568; Phenotypes: Microphthalmia MONDO:0021129, MAB21L1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia_Microphthalmia_Coloboma v1.60 MAB21L1 Zornitza Stark Phenotypes for gene: MAB21L1 were changed from Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479 to Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479; Microphthalmia MONDO:0021129, MAB21L1-related
Anophthalmia_Microphthalmia_Coloboma v1.59 MAB21L1 Zornitza Stark Publications for gene: MAB21L1 were set to 30487245
Anophthalmia_Microphthalmia_Coloboma v1.58 MAB21L1 Zornitza Stark Mode of inheritance for gene: MAB21L1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4935 MACF1 Lucy Spencer changed review comment from: Biallelic disease

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.

Neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant; to: Biallelic disease

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.

Neurodevelopmental disorder GREEN/AMBER:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant

Mostly missense reported with no functional, not a specific or very consistent phenotype.

Monoallelic:
There is a currently well established AD association with Lissencephaly 9 with complex brainstem malformation (MIM#618325) shown to have a GOF mechanism. But 2 recent papers PMID: 40925378 Dekker J 2025 and PMID: 41629993 Xi J 2026 have recently reported at least 6 de novo NMD variants in individuals with a nonspecific neurodevelopmental disorder. The pLI for this gene is 1 but there are quite a few NMD variants in gnomad with high het counts- however these cluster in exons 36-41 and exon 4 which are only coding in the MANE transcripts and not in other refseq transcripts or highly expressed transcripts in Gtex.
Rasopathy v0.114 RRAS Deepak Subramanian reviewed gene: RRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID:32815881, 34935735, 39725732; Phenotypes: Noonan syndrome, Myelodysplastic syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.225 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Monogenic Diabetes v0.224 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Intellectual disability syndromic and non-syndromic v1.807 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Intellectual disability syndromic and non-syndromic v1.806 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Disorders of immune dysregulation v1.46 RNU6ATAC Zornitza Stark Marked gene: RNU6ATAC as ready
Disorders of immune dysregulation v1.46 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Disorders of immune dysregulation v1.46 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Disorders of immune dysregulation v1.45 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Genetic Epilepsy v1.420 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Genetic Epilepsy v1.419 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Microcephaly v1.441 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Microcephaly v1.440 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Mendeliome v1.4935 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Syndromic disease, MONDO:0002254, RNU6ATAC-related to Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Mendeliome v1.4934 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed phenotypes: Mendez-Johnson immunoneurologic syndrome, MIM# 621585
Chromosome Breakage Disorders v1.29 FANCM Bryony Thompson Phenotypes for gene: FANCM were changed from Fanconi anaemia to FANCM Fanconi-like genomic instability disorder MONDO:0100578
Chromosome Breakage Disorders v1.29 FANCM Bryony Thompson Publications for gene: FANCM were set to 28837162
Chromosome Breakage Disorders v1.28 FANCM Bryony Thompson Classified gene: FANCM as Green List (high evidence)
Chromosome Breakage Disorders v1.28 FANCM Bryony Thompson Gene: fancm has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.27 FANCM Bryony Thompson reviewed gene: FANCM: Rating: GREEN; Mode of pathogenicity: None; Publications: 28837157, 28837162, 31942822, 34568721, 34793962, 37608704; Phenotypes: FANCM Fanconi-like genomic instability disorder MONDO:0100578; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4934 APBA1 Rylee Peters gene: APBA1 was added
gene: APBA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APBA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APBA1 were set to 42018264
Phenotypes for gene: APBA1 were set to Obesity disorder, MONDO:0011122, APBA1-related
Review for gene: APBA1 was set to AMBER
Added comment: PMID: 42018264 reports 2 individuals from 2 unrelated families with heterozygous APBA1 variants inherited from obese mothers, presenting with severe early‑onset obesity, hyperphagia and impaired expressive language development. The reported variants include one NMD-predicted variant and a +3 non-canonical splice site variant with an unknown splicing outcome adjacent to the penultimate exon which is in-frame.
Sources: Literature
Proteinuria v0.240 Sarah Milton Added reviews for gene NUP205 from panel Mendeliome
Mendeliome v1.4933 NUP205 Sarah Milton reviewed gene: NUP205: Rating: AMBER; Mode of pathogenicity: None; Publications: 31306055, 33065118, 36245711; Phenotypes: Nephrotic syndrome, type 13 MIM#616893, Visceral heterotaxy MONDO:0018677; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4933 ABCG2 Sarah Milton reviewed gene: ABCG2: Rating: RED; Mode of pathogenicity: None; Publications: 40082324, 33669292, 38379528, 38361420; Phenotypes: Uric acid concentration, serum, QTL1 MIM#138900, Junior blood group system MIM#614490; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v1.57 MAB21L1 Achchuthan Shanmugasundram commented on gene: MAB21L1: Biallelic variants in MAB21L1 are associated with a syndromic phenotype including ophthalmological presentations such as horizontal nystagmus, bilateral corneal opacities/ corneal dystrophy, strabismus and retinal degeneration. These phenotypes are not relevant for this panel.

However, there is sufficient evidence available for the association of monoallelic MAB21L1 variants with phenotypes relevant to this panel such as microphthalmia and aniridia.
Anophthalmia_Microphthalmia_Coloboma v1.57 MAB21L1 Achchuthan Shanmugasundram reviewed gene: MAB21L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27103078, 30487245, 33973683, 36413568, 36446583, 36892533, 39016008; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.806 Bryony Thompson Copied gene UBA7 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.806 UBA7 Bryony Thompson gene: UBA7 was added
gene: UBA7 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: UBA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBA7 were set to 42023152; 33710394; 28397838
Phenotypes for gene: UBA7 were set to Neurodevelopmental disorder, MONDO:0700092
Autism v0.252 Bryony Thompson Copied gene UBA7 from panel Mendeliome
Autism v0.252 UBA7 Bryony Thompson gene: UBA7 was added
gene: UBA7 was added to Autism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: UBA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBA7 were set to 42023152; 33710394; 28397838
Phenotypes for gene: UBA7 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4933 UBA7 Bryony Thompson Marked gene: UBA7 as ready
Mendeliome v1.4933 UBA7 Bryony Thompson Gene: uba7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4933 UBA7 Bryony Thompson Classified gene: UBA7 as Amber List (moderate evidence)
Mendeliome v1.4933 UBA7 Bryony Thompson Gene: uba7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4932 UBA7 Bryony Thompson gene: UBA7 was added
gene: UBA7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBA7 were set to 42023152; 33710394; 28397838
Phenotypes for gene: UBA7 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: UBA7 was set to AMBER
Added comment: PMID 33710394 reports a mosaic de novo splice variant in UBA7 causing moderate intellectual disability in a single individual. PMID 42023152 describes three individuals from three unrelated families with biallelic loss‑of‑function UBA7 truncating variants presenting with severe neurodevelopmental disorder, autism, seizures and dysmorphic features; cellular assays show loss of ISGylation but lack rescue experiments. The frameshift includes 1 homozygote in gnomAD and is more common than expected for a rare recessive disease. PMID 28397838 reports a consanguineous Pakistani family with a homozygous nonsense variant and a milder learning disability, but the variant’s high South‑Asian allele frequency challenges pathogenicity.
Sources: Literature
Mendeliome v1.4931 RPN1 Krithika Murali Marked gene: RPN1 as ready
Mendeliome v1.4931 RPN1 Krithika Murali Gene: rpn1 has been classified as Red List (Low Evidence).
Mendeliome v1.4931 RPN1 Krithika Murali gene: RPN1 was added
gene: RPN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPN1 were set to 41935956
Phenotypes for gene: RPN1 were set to Syndromic disease, MONDO:0002254
Review for gene: RPN1 was set to RED
Added comment: RPN1 encodes ribophorin I, a subunit of the oligosaccharyltransferase complex that mediates N‑linked protein glycosylation. PMID 41935956 report two affected siblings from a consanguineous family harbouring a homozygous nonsense variant c.1654C>T (p.Gln552*) who present with a congenital disorder of glycosylation characterised by neurodevelopmental delay, dysmorphic features and a type I transferrin profile. Biochemical analyses show a truncated RPN1 protein and reduced OST complex components, and CRISPR knock‑in of the variant in HEK293 cells reproduces the glycosylation defect, supporting a loss‑of‑function mechanism.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark Marked gene: ARHGEF6 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark Tag disputed was removed from gene: ARHGEF6.
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark changed review comment from: We have demoted this gene as Red considering some of the evidence was from cytogenetic abnormalities and other reported variants are now found to be present in the population at high frequency. OMIM number has been removed.

DISPUTED for association with ID.; to:
DISPUTED for association with ID.
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 Zornitza Stark Copied gene ARHGEF6 from panel Mendeliome
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark gene: ARHGEF6 was added
gene: ARHGEF6 was added to Congenital anomalies of the kidney and urinary tract (CAKUT). Sources: Expert Review Amber,Victorian Clinical Genetics Services
disputed tags were added to gene: ARHGEF6.
Mode of inheritance for gene: ARHGEF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARHGEF6 were set to 11017088; 36414417
Phenotypes for gene: ARHGEF6 were set to congenital anomaly of kidney and urinary tract, MONDO:0019719, ARHGEF6-related
Mendeliome v1.4930 ARHGEF6 Zornitza Stark Tag disputed was removed from gene: ARHGEF6.
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 Zornitza Stark Copied gene ARHGEF6 from panel Mendeliome
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.210 ARHGEF6 Zornitza Stark gene: ARHGEF6 was added
gene: ARHGEF6 was added to Congenital anomalies of the kidney and urinary tract (CAKUT). Sources: Expert Review Amber,Victorian Clinical Genetics Services
disputed tags were added to gene: ARHGEF6.
Mode of inheritance for gene: ARHGEF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARHGEF6 were set to 11017088; 36414417
Phenotypes for gene: ARHGEF6 were set to congenital anomaly of kidney and urinary tract, MONDO:0019719, ARHGEF6-related
Mendeliome v1.4930 ARHGEF6 Zornitza Stark Phenotypes for gene: ARHGEF6 were changed from MENTAL RETARDATION X-LINKED TYPE 46 to congenital anomaly of kidney and urinary tract, MONDO:0019719, ARHGEF6-related
Mendeliome v1.4929 ARHGEF6 Zornitza Stark Publications for gene: ARHGEF6 were set to 11017088
Mendeliome v1.4928 ARHGEF6 Zornitza Stark Classified gene: ARHGEF6 as Amber List (moderate evidence)
Mendeliome v1.4928 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4927 ARHGEF6 Zornitza Stark changed review comment from: We have demoted this gene as Red considering some of the evidence was from cytogenetic abnormalities and other reported variants are now found to be present in the population at high frequency. OMIM number has been removed.; to: We have demoted this gene as Red considering some of the evidence was from cytogenetic abnormalities and other reported variants are now found to be present in the population at high frequency. OMIM number has been removed.

DISPUTED for association with ID.
Mendeliome v1.4927 ARHGEF6 Zornitza Stark edited their review of gene: ARHGEF6: Added comment: PMID 36414417 reports 6 unrelated families (8 individuals) with hemizygous X‑linked ARHGEF6 variants and congenital anomalies of the kidneys and urinary tract (CAKUT). Loss‑of‑function truncating variants and one missense variant that segregates with three affected males provide. However, the missense variants have relatively high pop frequencies in gnomAD. Functional assays demonstrate loss of RAC1/CDC42 activation in cells and mouse/Xenopus knockouts recapitulate CAKUT.; Changed rating: AMBER; Changed publications: 36414417; Changed phenotypes: congenital anomaly of kidney and urinary tract, MONDO:0019719, ARHGEF6-related
Infertility and Recurrent Pregnancy Loss v1.165 AK7 Zornitza Stark Marked gene: AK7 as ready
Infertility and Recurrent Pregnancy Loss v1.165 AK7 Zornitza Stark Gene: ak7 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.165 Zornitza Stark Copied gene AK7 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.165 AK7 Zornitza Stark gene: AK7 was added
gene: AK7 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,ClinGen,ClinGen
disputed tags were added to gene: AK7.
Mode of inheritance for gene: AK7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK7 were set to 40376536; 39285691; 39254435; 38492416; 34854019; 34529793; 29365104
Phenotypes for gene: AK7 were set to spermatogenic failure 27, MONDO:0054731
Mendeliome v1.4927 AK7 Zornitza Stark changed review comment from: Four additional unrelated families with biallelic AK7 variants and male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) reported (PMID 34854019 – homozygous p.E616K missense; PMID 38492416 – homozygous p.Lys385* nonsense; PMID 29365104 – homozygous p.Leu673Pro missense; PMID 39254435 – homozygous splice‑site c.871‑4ACA>A). Functional assays consistently show loss of AK7 protein in patient sperm and disrupted axonemal structure.; to: Four additional unrelated families with biallelic AK7 variants and male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) reported (PMID 34854019 – homozygous p.E616K missense; PMID 38492416 – homozygous p.Lys385* nonsense; PMID 29365104 – homozygous p.Leu673Pro missense; PMID 39254435 – homozygous splice‑site c.871‑4ACA>A). Functional assays consistently show loss of AK7 protein in patient sperm and disrupted axonemal structure.

DISPUTED by ClinGen for the association with PCD.

LIMITED by ClinGen for the association with spermatogenic failure but in 2023. The two most recent papers not considered as part of the curation.
Mendeliome v1.4927 AK7 Zornitza Stark Publications for gene: AK7 were set to
Mendeliome v1.4926 AK7 Zornitza Stark Phenotypes for gene: AK7 were changed from Primary ciliary dyskinesia, MONDO:0016575 to spermatogenic failure 27, MONDO:0054731
Mendeliome v1.4925 AK7 Zornitza Stark Classified gene: AK7 as Green List (high evidence)
Mendeliome v1.4925 AK7 Zornitza Stark Gene: ak7 has been classified as Green List (High Evidence).
Mendeliome v1.4924 AK7 Zornitza Stark reviewed gene: AK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 40376536, 39285691, 39254435, 38492416, 34854019, 34529793, 29365104; Phenotypes: spermatogenic failure 27, MONDO:0054731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v1.31 MYH7B Zornitza Stark Classified gene: MYH7B as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v1.31 MYH7B Zornitza Stark Gene: myh7b has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v1.30 MYH7B Zornitza Stark All sources for gene: MYH7B were removed
Hypertrophic cardiomyopathy v1.29 MYH7B Zornitza Stark edited their review of gene: MYH7B: Changed publications: 32207065
Hypertrophic cardiomyopathy v1.29 MYH7B Zornitza Stark Marked gene: MYH7B as ready
Hypertrophic cardiomyopathy v1.29 MYH7B Zornitza Stark Gene: myh7b has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v1.29 MYH7B Zornitza Stark Phenotypes for gene: MYH7B were changed from Hypertrophic cardiomyopathy, MONDO:0005045, MYH7B-related; Hearing loss disorder, MONDO:0005365, MYH7B-related to Hypertrophic cardiomyopathy, MONDO:0005045, MYH7B-related
Hypertrophic cardiomyopathy v1.28 MYH7B Zornitza Stark Publications for gene: MYH7B were set to 36963494; 32207065; 26752647; 25528277
Hypertrophic cardiomyopathy v1.27 MYH7B Zornitza Stark Deleted their comment
Hypertrophic cardiomyopathy v1.27 MYH7B Zornitza Stark changed review comment from: PMID 32207065 reports 4 families with heterozygous MYH7B loss‑of‑function variants causing hypertrophic cardiomyopathy (HCM) and provides variant‑specific expression loss plus a Myh7b knockout rat model.

PMID 36963494 and PMID 25528277 describe the same autosomal‑recessive MYH7B hearing‑loss family (3 affected siblings) and present biochemical assays for two missense variants, expanding the phenotypic spectrum to severe sensorineural hearing loss with ocular anomalies.

PMID 26752647 reports a homozygous missense MYH7B variant in a child with arthrogryposis and cardiomyopathy, adding a novel recessive syndrome.

The bi-allelic association is RED.; to: PMID 32207065 reports 4 families with heterozygous MYH7B loss‑of‑function variants causing hypertrophic cardiomyopathy (HCM) and provides variant‑specific expression loss plus a Myh7b knockout rat model.
Hypertrophic cardiomyopathy v1.27 Zornitza Stark Copied gene MYH7B from panel Mendeliome
Hypertrophic cardiomyopathy v1.27 MYH7B Zornitza Stark gene: MYH7B was added
gene: MYH7B was added to Hypertrophic cardiomyopathy. Sources: Expert Review Amber,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYH7B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7B were set to 36963494; 32207065; 26752647; 25528277
Phenotypes for gene: MYH7B were set to Hypertrophic cardiomyopathy, MONDO:0005045, MYH7B-related; Hearing loss disorder, MONDO:0005365, MYH7B-related
Mendeliome v1.4924 MYH7B Zornitza Stark Phenotypes for gene: MYH7B were changed from to Hypertrophic cardiomyopathy, MONDO:0005045, MYH7B-related; Hearing loss disorder, MONDO:0005365, MYH7B-related
Mendeliome v1.4923 MYH7B Zornitza Stark Publications for gene: MYH7B were set to
Mendeliome v1.4922 MYH7B Zornitza Stark Mode of inheritance for gene: MYH7B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4921 MYH7B Zornitza Stark Classified gene: MYH7B as Amber List (moderate evidence)
Mendeliome v1.4921 MYH7B Zornitza Stark Gene: myh7b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4920 MYH7B Zornitza Stark edited their review of gene: MYH7B: Added comment: PMID 32207065 reports 4 families with heterozygous MYH7B loss‑of‑function variants causing hypertrophic cardiomyopathy (HCM) and provides variant‑specific expression loss plus a Myh7b knockout rat model.

PMID 36963494 and PMID 25528277 describe the same autosomal‑recessive MYH7B hearing‑loss family (3 affected siblings) and present biochemical assays for two missense variants, expanding the phenotypic spectrum to severe sensorineural hearing loss with ocular anomalies.

PMID 26752647 reports a homozygous missense MYH7B variant in a child with arthrogryposis and cardiomyopathy, adding a novel recessive syndrome.

The bi-allelic association is RED.; Changed rating: AMBER; Changed publications: 36963494, 32207065, 26752647, 25528277; Changed phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045, MYH7B-related, Hearing loss disorder, MONDO:0005365, MYH7B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Defects of intrinsic and innate immunity v1.42 IL12RB2 Zornitza Stark edited their review of gene: IL12RB2: Changed phenotypes: Immunodeficiency disease MONDO:0021094, IL12RB1-related
Defects of intrinsic and innate immunity v1.42 IL12RB2 Zornitza Stark Phenotypes for gene: IL12RB2 were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease MONDO:0021094, IL12RB1-related; Susceptibility to mycobacteria and Salmonella
Defects of intrinsic and innate immunity v1.41 IL12RB2 Zornitza Stark Publications for gene: IL12RB2 were set to 30578351
Defects of intrinsic and innate immunity v1.40 IL12RB2 Zornitza Stark Mode of inheritance for gene: IL12RB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.39 IL12RB2 Zornitza Stark edited their review of gene: IL12RB2: Added comment: PMID 31158284 reports single individual with high impact variant and Mendelian Susceptibility to Mycobacterial Disease (MSMD). PMID 42012883 reports two individuals with disseminated coccidioidomycosis and missense variants but one of these has an implausibly high population frequency.; Changed publications: 30578351, 31158284, 42012883; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4920 IL12RB2 Zornitza Stark Publications for gene: IL12RB2 were set to 30578351
Mendeliome v1.4919 IL12RB2 Zornitza Stark Mode of inheritance for gene: IL12RB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4918 IL12RB2 Zornitza Stark edited their review of gene: IL12RB2: Added comment: PMID 31158284 reports single individual with high impact variant and Mendelian Susceptibility to Mycobacterial Disease (MSMD).
PMID 42012883 reports two individuals with disseminated coccidioidomycosis and missense variants but one of these has an implausibly high population frequency.; Changed publications: 30578351, 31158284, 42012883; Changed phenotypes: Inborn error of immunity, MONDO:0003778, IL12RB2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.805 Zornitza Stark Copied gene MELK from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.805 MELK Zornitza Stark gene: MELK was added
gene: MELK was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MELK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MELK were set to 41973119
Phenotypes for gene: MELK were set to Neurodevelopmental disorder, MONDO:0700092, MELK-related
Autism v0.251 Zornitza Stark Copied gene MELK from panel Mendeliome
Autism v0.251 MELK Zornitza Stark gene: MELK was added
gene: MELK was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MELK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MELK were set to 41973119
Phenotypes for gene: MELK were set to Neurodevelopmental disorder, MONDO:0700092, MELK-related
Infertility and Recurrent Pregnancy Loss v1.164 Sangavi Sivagnanasundram Added reviews for gene NUP210L from panel Mendeliome
Mendeliome v1.4918 NUP210L Sangavi Sivagnanasundram reviewed gene: NUP210L: Rating: GREEN; Mode of pathogenicity: None; Publications: 42055687, 33332558; Phenotypes: spermatogenic failure, MONDO:0004983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4918 MELK Zornitza Stark changed review comment from: PMID 41973119 reports four unrelated individuals from four families each carrying a heterozygous loss‑of‑function MELK variant (stop‑gain or start‑loss) and presenting with autism spectrum disorder (ASD). Mouse cortex MELK knockdown replicates cortical progenitor defects, and the authors propose MELK haploinsufficiency as a rare risk factor for ASD.

Parental segregation information lacking. One of the variants is present in 10 hets in gnomAD.
Sources: Literature; to: PMID 41973119 reports four unrelated individuals from four families each carrying a heterozygous loss‑of‑function MELK variant (stop‑gain or start‑loss) and presenting with autism spectrum disorder (ASD). Mouse cortex MELK knockdown replicates cortical progenitor defects, and the authors propose MELK haploinsufficiency as a rare risk factor for ASD.

Parental segregation information lacking. One of the variants is present in 10 hets in gnomAD. Plenty of other LoF in gnomAD.

Sources: Literature
Mendeliome v1.4918 MELK Zornitza Stark Marked gene: MELK as ready
Mendeliome v1.4918 MELK Zornitza Stark Gene: melk has been classified as Red List (Low Evidence).
Mendeliome v1.4918 MELK Zornitza Stark gene: MELK was added
gene: MELK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MELK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MELK were set to 41973119
Phenotypes for gene: MELK were set to Neurodevelopmental disorder, MONDO:0700092, MELK-related
Review for gene: MELK was set to RED
Added comment: PMID 41973119 reports four unrelated individuals from four families each carrying a heterozygous loss‑of‑function MELK variant (stop‑gain or start‑loss) and presenting with autism spectrum disorder (ASD). Mouse cortex MELK knockdown replicates cortical progenitor defects, and the authors propose MELK haploinsufficiency as a rare risk factor for ASD.

Parental segregation information lacking. One of the variants is present in 10 hets in gnomAD.
Sources: Literature
Mendeliome v1.4917 ANAPC13 Zornitza Stark Marked gene: ANAPC13 as ready
Mendeliome v1.4917 ANAPC13 Zornitza Stark Gene: anapc13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4917 Zornitza Stark Copied gene ANAPC13 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4917 ANAPC13 Zornitza Stark gene: ANAPC13 was added
gene: ANAPC13 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ANAPC13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC13 were set to 41997520
Phenotypes for gene: ANAPC13 were set to Infertility disorder, MONDO:0005047, ANAPC13-related
Infertility and Recurrent Pregnancy Loss v1.163 ANAPC13 Zornitza Stark Marked gene: ANAPC13 as ready
Infertility and Recurrent Pregnancy Loss v1.163 ANAPC13 Zornitza Stark Gene: anapc13 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.163 ANAPC13 Zornitza Stark Classified gene: ANAPC13 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.163 ANAPC13 Zornitza Stark Gene: anapc13 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.162 ANAPC13 Zornitza Stark gene: ANAPC13 was added
gene: ANAPC13 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ANAPC13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC13 were set to 41997520
Phenotypes for gene: ANAPC13 were set to Infertility disorder, MONDO:0005047, ANAPC13-related
Review for gene: ANAPC13 was set to AMBER
Added comment: Three individuals reported with biallelic variants in this gene and oocyte maturation arrest. Two missense variants across the three cases. Supportive functional work including mouse model.
Sources: Literature
Mendeliome v1.4916 CDK5RAP3 Sangavi Sivagnanasundram changed review comment from: CDK5RAP3 functions as a regulator that restricts UFMylation which is important for protein function.
No pathogenic variants reported in ClinVar across the gene. Currently, no OMIM entry for this GDA.

This publication reports two probands with a severe neurodevelopmental disorder. Affected probands presented with foetal growth restriction, foetal akinesia, pontocerebellar hypoplasia, arthrogryposis and hepatic pathology. A homozygous deep‑intronic splice variant (c.334+243G>A) was identified in both probands.
Supportive function assay showed loss of CDK5RAP3 protein and rescue by antisense-oligonucleotides however only one patient-derived cell line was used.

Gene to be RED. More evidence is required to upgrade to AMBER.
Sources: Literature; to: CDK5RAP3 functions as a regulator that restricts UFMylation which is important for protein function.
No pathogenic variants reported in ClinVar across the gene. Currently, no OMIM entry for this GDA.

This publication reports two probands with a severe neurodevelopmental disorder. Affected probands presented with foetal growth restriction, foetal akinesia, pontocerebellar hypoplasia, arthrogryposis and hepatic pathology. A homozygous deep‑intronic splice variant (c.334+243G>A) was identified in both probands.
Supportive function assay showed loss of CDK5RAP3 protein and rescue by antisense-oligonucleotides however only one patient-derived cell line was used.

Gene to be RED. More evidence is required to upgrade to the GDA.
Sources: Literature
Mendeliome v1.4916 CDK5RAP3 Sangavi Sivagnanasundram gene: CDK5RAP3 was added
gene: CDK5RAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK5RAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5RAP3 were set to 42045457
Phenotypes for gene: CDK5RAP3 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CDK5RAP3 was set to RED
Added comment: CDK5RAP3 functions as a regulator that restricts UFMylation which is important for protein function.
No pathogenic variants reported in ClinVar across the gene. Currently, no OMIM entry for this GDA.

This publication reports two probands with a severe neurodevelopmental disorder. Affected probands presented with foetal growth restriction, foetal akinesia, pontocerebellar hypoplasia, arthrogryposis and hepatic pathology. A homozygous deep‑intronic splice variant (c.334+243G>A) was identified in both probands.
Supportive function assay showed loss of CDK5RAP3 protein and rescue by antisense-oligonucleotides however only one patient-derived cell line was used.

Gene to be RED. More evidence is required to upgrade to AMBER.
Sources: Literature
Mendeliome v1.4915 C17orf74 Zornitza Stark Marked gene: C17orf74 as ready
Mendeliome v1.4915 C17orf74 Zornitza Stark Gene: c17orf74 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4915 Zornitza Stark Copied gene C17orf74 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4915 C17orf74 Zornitza Stark gene: C17orf74 was added
gene: C17orf74 was added to Mendeliome. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf74.
Mode of inheritance for gene: C17orf74 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C17orf74 were set to 42028965
Phenotypes for gene: C17orf74 were set to Infertility disorder, MONDO:0005047, c17orf74-related
Microcephaly v1.440 Lucy Spencer Copied gene CECR2 from panel Mendeliome
Microcephaly v1.440 CECR2 Lucy Spencer gene: CECR2 was added
gene: CECR2 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CECR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CECR2 were set to 41964217; 37424722
Phenotypes for gene: CECR2 were set to Neurodevelopmental disorder, MONDO:0700092, CECR2-related; neural tube defects, susceptibility to MONDO:0020705, CECR2-related
Intellectual disability syndromic and non-syndromic v1.804 Lucy Spencer Copied gene CECR2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.804 CECR2 Lucy Spencer gene: CECR2 was added
gene: CECR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CECR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CECR2 were set to 41964217; 37424722
Phenotypes for gene: CECR2 were set to Neurodevelopmental disorder, MONDO:0700092, CECR2-related; neural tube defects, susceptibility to MONDO:0020705, CECR2-related
Genetic Epilepsy v1.419 Lucy Spencer Copied gene CECR2 from panel Mendeliome
Genetic Epilepsy v1.419 CECR2 Lucy Spencer gene: CECR2 was added
gene: CECR2 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CECR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CECR2 were set to 41964217; 37424722
Phenotypes for gene: CECR2 were set to Neurodevelopmental disorder, MONDO:0700092, CECR2-related; neural tube defects, susceptibility to MONDO:0020705, CECR2-related
Growth failure v1.109 Sarah Milton Copied gene ERBB2 from panel Mendeliome
Growth failure v1.109 ERBB2 Sarah Milton gene: ERBB2 was added
gene: ERBB2 was added to Growth failure. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Clefting disorders v0.319 Sarah Milton Copied gene ERBB2 from panel Mendeliome
Clefting disorders v0.319 ERBB2 Sarah Milton gene: ERBB2 was added
gene: ERBB2 was added to Clefting disorders. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Mendeliome v1.4914 ERBB2 Sarah Milton reviewed gene: ERBB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 42060361; Phenotypes: Syndromic disease, MONDO:0002254, ERBB2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4914 CECR2 Lucy Spencer Classified gene: CECR2 as Green List (high evidence)
Mendeliome v1.4914 CECR2 Lucy Spencer Gene: cecr2 has been classified as Green List (High Evidence).
Mendeliome v1.4913 CECR2 Lucy Spencer gene: CECR2 was added
gene: CECR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CECR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CECR2 were set to 41964217; 37424722
Phenotypes for gene: CECR2 were set to Neurodevelopmental disorder, MONDO:0700092, CECR2-related; neural tube defects, susceptibility to MONDO:0020705, CECR2-related
Review for gene: CECR2 was set to GREEN
Added comment: PMID 41964217 reports six individuals from six unrelated families with heterozygous nonsense, frameshift or missense CECR2 variants causing a neurodevelopmental disorder characterized by developmental and speech delay, growth restriction, microcephaly/small head circumference, intellectual disability and variable congenital anomalies. Other common features included gastrointestinal dysmotility, abnormal brain morphology, cardiac anomalies, ophthalmologic anomalies, and seizures/epilepsy in 3 patients. Two variants were confirmed de novo (1 missense 1 nonsense), inheritance information was no available for the other 4. All variant were either absent from gnomad v4 or had only 1 het. all missense were towards the end of the protein p.1385-1428.

PMID 37424722 9 CECR2 variants in 12 patients with neural tube defects. All variants were missense from p. 327-1023 and 5 of them had over 11 hets in gnomad. Phenotypes included anencephaly, hydrocephalus, spina bifida, atelectasis, visceral congestion and more. The paper mentions a mouse model has previous shown LOF of CECR2 results in NTDs and that high homocysteine levels could further reduce CECR2 expression. Functional analysis on 4 missense in this cohort showed reduced CECR2 protein expression on western blot for 3, exposure to homocysteine thiolactone further reduced this expression in increase apoptosis activity while folic acid supplementation counteracted CECR2 expression decline and reduced apoptosis. No inheritance information was available for these variants.

Green for the neurodevelopmental disorder, amber/red for neural tube defects similar to other genes with this association ie VANGL2.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.161 C17orf74 Zornitza Stark changed review comment from: Four males reported with heterozygous variants in this gene and oligoasthenoteratozoospermia (OAT). Some functional data presented.
Sources: Literature; to: Four males reported with heterozygous variants in this gene and oligoasthenoteratozoospermia (OAT). Some functional data presented.

HGNC approved name is SPEM2.

Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.161 C17orf74 Zornitza Stark Marked gene: C17orf74 as ready
Infertility and Recurrent Pregnancy Loss v1.161 C17orf74 Zornitza Stark Gene: c17orf74 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.161 C17orf74 Zornitza Stark Classified gene: C17orf74 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.161 C17orf74 Zornitza Stark Gene: c17orf74 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.160 C17orf74 Zornitza Stark gene: C17orf74 was added
gene: C17orf74 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
new gene name tags were added to gene: C17orf74.
Mode of inheritance for gene: C17orf74 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C17orf74 were set to 42028965
Phenotypes for gene: C17orf74 were set to Infertility disorder, MONDO:0005047, c17orf74-related
Review for gene: C17orf74 was set to AMBER
Added comment: Four males reported with heterozygous variants in this gene and oligoasthenoteratozoospermia (OAT). Some functional data presented.
Sources: Literature
Mendeliome v1.4912 PTGIS Zornitza Stark Marked gene: PTGIS as ready
Mendeliome v1.4912 PTGIS Zornitza Stark Gene: ptgis has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4912 Zornitza Stark Copied gene PTGIS from panel Stroke
Mendeliome v1.4912 PTGIS Zornitza Stark gene: PTGIS was added
gene: PTGIS was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PTGIS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTGIS were set to 42033196
Phenotypes for gene: PTGIS were set to Vascular disorder, MONDO:0005385, PTGIS-related
Stroke v1.50 PTGIS Zornitza Stark changed review comment from: Five individuals from four families reported with biallelic variants in this gene and recurrent cervical internal carotid artery vasospasm (RCICAV). Three different LoF variants observed in compound het or homozygous state. Human carotid artery endothelial cells expressing these truncated variants exhibited markedly reduced PTGIS protein and prostacyclin metabolite production. Prostacyclin is a potent vasodilator, hence impaired biosynthesis is consistent with predisposition to vasospasm.
Sources: Literature; to: Five individuals from four families reported with biallelic variants in this gene and recurrent cervical internal carotid artery vasospasm (RCICAV). Three different LoF variants observed in compound het or homozygous state. Human carotid artery endothelial cells expressing these truncated variants exhibited markedly reduced PTGIS protein and prostacyclin metabolite production. Prostacyclin is a potent vasodilator, hence impaired biosynthesis is consistent with predisposition to vasospasm.

Amber rating as recurrent rather than unique variants across the families and stroke is usually a multifactorial condition.

Sources: Literature
Stroke v1.50 PTGIS Zornitza Stark Marked gene: PTGIS as ready
Stroke v1.50 PTGIS Zornitza Stark Gene: ptgis has been classified as Amber List (Moderate Evidence).
Stroke v1.50 PTGIS Zornitza Stark Classified gene: PTGIS as Amber List (moderate evidence)
Stroke v1.50 PTGIS Zornitza Stark Gene: ptgis has been classified as Amber List (Moderate Evidence).
Stroke v1.49 PTGIS Zornitza Stark gene: PTGIS was added
gene: PTGIS was added to Stroke. Sources: Literature
Mode of inheritance for gene: PTGIS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTGIS were set to 42033196
Phenotypes for gene: PTGIS were set to Vascular disorder, MONDO:0005385, PTGIS-related
Review for gene: PTGIS was set to AMBER
Added comment: Five individuals from four families reported with biallelic variants in this gene and recurrent cervical internal carotid artery vasospasm (RCICAV). Three different LoF variants observed in compound het or homozygous state. Human carotid artery endothelial cells expressing these truncated variants exhibited markedly reduced PTGIS protein and prostacyclin metabolite production. Prostacyclin is a potent vasodilator, hence impaired biosynthesis is consistent with predisposition to vasospasm.
Sources: Literature
Disorders of immune dysregulation v1.45 TLR1 Zornitza Stark Marked gene: TLR1 as ready
Disorders of immune dysregulation v1.45 TLR1 Zornitza Stark Gene: tlr1 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v1.45 TLR1 Zornitza Stark Phenotypes for gene: TLR1 were changed from Leprosy, protection against} {Leprosy, susceptibility to, 5} MIM#613223; Inborn error of immunity, MONDO:0003778, TLR1-related to Inborn error of immunity, MONDO:0003778, TLR1-related
Disorders of immune dysregulation v1.44 Zornitza Stark Copied gene TLR1 from panel Mendeliome
Disorders of immune dysregulation v1.44 TLR1 Zornitza Stark gene: TLR1 was added
gene: TLR1 was added to Disorders of immune dysregulation. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: TLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TLR1 were set to 42048460
Phenotypes for gene: TLR1 were set to Leprosy, protection against} {Leprosy, susceptibility to, 5} MIM#613223; Inborn error of immunity, MONDO:0003778, TLR1-related
Mendeliome v1.4911 TLR1 Zornitza Stark Phenotypes for gene: TLR1 were changed from Leprosy, protection against} {Leprosy, susceptibility to, 5} MIM#613223 to Leprosy, protection against} {Leprosy, susceptibility to, 5} MIM#613223; Inborn error of immunity, MONDO:0003778, TLR1-related
Mendeliome v1.4910 TLR1 Zornitza Stark Publications for gene: TLR1 were set to
Mendeliome v1.4909 TLR1 Zornitza Stark Mode of inheritance for gene: TLR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4908 TLR1 Zornitza Stark reviewed gene: TLR1: Rating: RED; Mode of pathogenicity: None; Publications: 42048460; Phenotypes: Inborn error of immunity, MONDO:0003778, TLR1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.233 TNNI3 Zornitza Stark Marked gene: TNNI3 as ready
Cardiomyopathy_Paediatric v0.233 TNNI3 Zornitza Stark Gene: tnni3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.233 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from Cardiomyopathy, dilated, 2A,; Cardiomyopathy, familial hypertrophic, 7; Cardiomyopathy, dilated, 1FF; Hypertrophic cardiomyopathy to Cardiomyopathy, dilated, 1FF, MIM#613286 Cardiomyopathy, hypertrophic, 7, MIM# 613690 Cardiomyopathy, familial restrictive, MIM#1115210
Cardiomyopathy_Paediatric v0.232 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to
Cardiomyopathy_Paediatric v0.231 TNNI3 Zornitza Stark edited their review of gene: TNNI3: Changed phenotypes: Cardiomyopathy, dilated, 1FF, MIM#613286 Cardiomyopathy, hypertrophic, 7, MIM# 613690 Cardiomyopathy, familial restrictive, MIM#1115210
Cardiomyopathy_Paediatric v0.231 TNNI3 Zornitza Stark reviewed gene: TNNI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35838873, 41918167; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4908 THRB Zornitza Stark Phenotypes for gene: THRB were changed from Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650 to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650; Macular dystrophy, MONDO:0031166, THRB-related
Mendeliome v1.4907 THRB Zornitza Stark Publications for gene: THRB were set to 25135573; 31590893
Mendeliome v1.4906 THRB Zornitza Stark edited their review of gene: THRB: Changed publications: 25135573, 31590893, 40295579
Mendeliome v1.4906 THRB Zornitza Stark changed review comment from: 12 individuals with macular dystrophy from 3 families reported with variants in THRB. Two families had the variant NM_001354712.2:c.283 + 1G > A, and one the novel variant NM_001354712.2:c.283G > A. Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants, possibly suggestive of GoF mechanism.; to: 12 individuals with macular dystrophy from 3 families reported with variants in THRB. Two families had the variant NM_001354712.2:c.283 + 1G > A, and one the novel variant NM_001354712.2:c.283G > A. Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants, possibly suggestive of GoF mechanism.

AMBER for this association.
Mendeliome v1.4906 THRB Zornitza Stark edited their review of gene: THRB: Added comment: 12 individuals with macular dystrophy from 3 families reported with variants in THRB. Two families had the variant NM_001354712.2:c.283 + 1G > A, and one the novel variant NM_001354712.2:c.283G > A. Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants, possibly suggestive of GoF mechanism.; Changed phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650, Macular dystrophy, MONDO:0031166, THRB-related
Mendeliome v1.4906 Zornitza Stark Added reviews for gene THRB from panel Macular Dystrophy/Stargardt Disease
Macular Dystrophy/Stargardt Disease v0.62 THRB Zornitza Stark Marked gene: THRB as ready
Macular Dystrophy/Stargardt Disease v0.62 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.62 THRB Zornitza Stark Classified gene: THRB as Amber List (moderate evidence)
Macular Dystrophy/Stargardt Disease v0.62 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.61 THRB Zornitza Stark gene: THRB was added
gene: THRB was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: THRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THRB were set to 40295579
Phenotypes for gene: THRB were set to Macular dystrophy, MONDO:0031166, THRB-related
Review for gene: THRB was set to AMBER
Added comment: 12 individuals with macular dystrophy from 3 families reported with variants in THRB. Two families had the variant NM_001354712.2:c.283 + 1G > A, and one the novel variant NM_001354712.2:c.283G > A. Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants, possibly suggestive of GoF mechanism.
Sources: Literature
Mendeliome v1.4905 RHEB Zornitza Stark Phenotypes for gene: RHEB were changed from Neurodevelopmental disorder MONDO:0700092, RHEB-related; Intellectual disability; Macrocephaly; Focal cortical dysplasia to Neurodevelopmental disorder MONDO:0700092, RHEB-related; Intellectual disability; Macrocephaly; Focal cortical dysplasia, MONDO:0019009, RHEB-related
Mendeliome v1.4904 RHEB Zornitza Stark edited their review of gene: RHEB: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, RHEB-related, Intellectual disability, Macrocephaly, Focal cortical dysplasia, MONDO:0019009, RHEB-related
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.50 RHEB Zornitza Stark Marked gene: RHEB as ready
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.50 RHEB Zornitza Stark Gene: rheb has been classified as Amber List (Moderate Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.50 RHEB Zornitza Stark Classified gene: RHEB as Amber List (moderate evidence)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.50 RHEB Zornitza Stark Gene: rheb has been classified as Amber List (Moderate Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.49 RHEB Zornitza Stark gene: RHEB was added
gene: RHEB was added to Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly. Sources: Literature
somatic tags were added to gene: RHEB.
Mode of inheritance for gene: RHEB was set to Other
Publications for gene: RHEB were set to 41940182; 35687047
Phenotypes for gene: RHEB were set to Focal cortical dysplasia, MONDO:0019009, RHEB-related
Review for gene: RHEB was set to AMBER
Added comment: Somatic mosaic RHEB variants causing focal cortical dysplasia type IIa/IIb were reported in two independent individuals (PMIDs 41940182, 35687047)
Sources: Literature
Mendeliome v1.4904 RHEB Zornitza Stark Tag somatic tag was added to gene: RHEB.
Mendeliome v1.4904 RHEB Zornitza Stark edited their review of gene: RHEB: Added comment: Somatic mosaic RHEB variants causing focal cortical dysplasia type IIa/IIb were reported in two independent individuals (PMIDs 41940182, 35687047); Changed publications: 31337748, 29051493, 39993836, 41940182, 35687047
Mendeliome v1.4904 RHEB Zornitza Stark edited their review of gene: RHEB: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4904 MLH3 Zornitza Stark Marked gene: MLH3 as ready
Mendeliome v1.4904 MLH3 Zornitza Stark Gene: mlh3 has been classified as Green List (High Evidence).
Mendeliome v1.4904 Zornitza Stark Copied gene MLH3 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4904 MLH3 Zornitza Stark gene: MLH3 was added
gene: MLH3 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: MLH3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLH3 were set to 2000973; 41102564; 33517345; 32469048
Phenotypes for gene: MLH3 were set to Infertility disorder, MONDO:0005047, MLH3-related
Infertility and Recurrent Pregnancy Loss v1.159 MLH3 Zornitza Stark Marked gene: MLH3 as ready
Infertility and Recurrent Pregnancy Loss v1.159 MLH3 Zornitza Stark Gene: mlh3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.159 MLH3 Zornitza Stark Classified gene: MLH3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.159 MLH3 Zornitza Stark Gene: mlh3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.158 MLH3 Zornitza Stark gene: MLH3 was added
gene: MLH3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: MLH3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLH3 were set to 2000973; 41102564; 33517345; 32469048
Phenotypes for gene: MLH3 were set to Infertility disorder, MONDO:0005047, MLH3-related
Review for gene: MLH3 was set to GREEN
Added comment: PMIDs 42000973, 41102564, 33517345 and 32469048 collectively report 12 individuals from 11 unrelated families with biallelic loss‑of‑function MLH3 variants causing early embryonic arrest (4 families), unexplained recurrent pregnancy loss (5 families), severe oligozoospermia (1 family) and non‑obstructive azoospermia (1 family). Functional studies in mouse or cell models show impaired gametogenesis.
Sources: Literature
Incidentalome v0.436 MLH3 Zornitza Stark Marked gene: MLH3 as ready
Incidentalome v0.436 MLH3 Zornitza Stark Gene: mlh3 has been classified as Red List (Low Evidence).
Incidentalome v0.436 MLH3 Zornitza Stark Phenotypes for gene: MLH3 were changed from to Colorectal cancer, hereditary nonpolyposis, type 7, MIM# 614385
Incidentalome v0.435 MLH3 Zornitza Stark Mode of inheritance for gene: MLH3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.434 MLH3 Zornitza Stark Classified gene: MLH3 as Red List (low evidence)
Incidentalome v0.434 MLH3 Zornitza Stark Gene: mlh3 has been classified as Red List (Low Evidence).
Incidentalome v0.433 MLH3 Zornitza Stark reviewed gene: MLH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorectal cancer, hereditary nonpolyposis, type 7, MIM# 614385; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.803 MACF1 Lucy Spencer Phenotypes for gene: MACF1 were changed from Lissencephaly 9 with complex brainstem malformation, MIM# 618325 to Lissencephaly 9 with complex brainstem malformation, MIM#618325; Neurodevelopmental disorder (MONDO:0700092), MACF1-related
Intellectual disability syndromic and non-syndromic v1.802 MACF1 Lucy Spencer Mode of inheritance for gene: MACF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.801 Lucy Spencer Added reviews for gene MACF1 from panel Mendeliome
Genetic Epilepsy v1.418 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.417 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.416 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4903 ITGAL Zornitza Stark Marked gene: ITGAL as ready
Mendeliome v1.4903 ITGAL Zornitza Stark Gene: itgal has been classified as Green List (High Evidence).
Mendeliome v1.4903 Zornitza Stark Copied gene ITGAL from panel Susceptibility to Viral Infections
Mendeliome v1.4903 ITGAL Zornitza Stark gene: ITGAL was added
gene: ITGAL was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ITGAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAL were set to 41758928
Phenotypes for gene: ITGAL were set to Epidermodysplasia verruciformis, susceptibility to, 6, MIM#621588
Susceptibility to Viral Infections v1.12 ITGAL Zornitza Stark Marked gene: ITGAL as ready
Susceptibility to Viral Infections v1.12 ITGAL Zornitza Stark Gene: itgal has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v1.12 ITGAL Zornitza Stark Classified gene: ITGAL as Green List (high evidence)
Susceptibility to Viral Infections v1.12 ITGAL Zornitza Stark Gene: itgal has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v1.11 ITGAL Zornitza Stark gene: ITGAL was added
gene: ITGAL was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: ITGAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAL were set to 41758928
Phenotypes for gene: ITGAL were set to Epidermodysplasia verruciformis, susceptibility to, 6, MIM#621588
Review for gene: ITGAL was set to GREEN
Added comment: 6 individuals from 4 families, including 2 parent-child pairs reported with biallelic variants in this gene and susceptibility to HPV resulting in lifelong occurrence of disseminated flat warts. Some supportive functional data.

Three different homozygous variants identified, two LoF and one missense.
Sources: Literature
Dystonia and Chorea v0.348 CACNA1B Zornitza Stark Marked gene: CACNA1B as ready
Dystonia and Chorea v0.348 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Red List (Low Evidence).
Mitochondrial disease v1.24 TMEM65 Zornitza Stark Publications for gene: TMEM65 were set to 28295037
Mitochondrial disease v1.23 TMEM65 Zornitza Stark edited their review of gene: TMEM65: Added comment: PMID 41980949 provides mouse whole‑body, neuronal‑specific and skeletal‑muscle‑specific TMEM65 knockout models that recapitulate severe mitochondrial encephalomyopathy and adult‑onset myopathy; rescue of early lethality by MCU knockout demonstrates that loss‑of‑function of TMEM65 is pathogenic.; Changed publications: 28295037, 41980949
Mendeliome v1.4902 TMEM65 Zornitza Stark edited their review of gene: TMEM65: Changed rating: AMBER
Mendeliome v1.4902 TMEM65 Zornitza Stark edited their review of gene: TMEM65: Added comment: PMID 41980949 provides mouse whole‑body, neuronal‑specific and skeletal‑muscle‑specific TMEM65 knockout models that recapitulate severe mitochondrial encephalomyopathy and adult‑onset myopathy; rescue of early lethality by MCU knockout demonstrates that loss‑of‑function of TMEM65 is pathogenic.; Changed rating: RED; Changed publications: 41980949; Changed phenotypes: Mitochondrial disease, MONDO:0044970
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.365 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Gastrointestinal neuromuscular disease v1.32 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v1.31 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 40329538; 33720042
Gastrointestinal neuromuscular disease v1.30 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623) to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.366 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Gastrointestinal neuromuscular disease v1.29 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v1.28 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Gastrointestinal neuromuscular disease v1.27 ERBB2 Chirag Patel Marked gene: ERBB2 as ready
Gastrointestinal neuromuscular disease v1.28 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v1.27 ERBB2 Chirag Patel Gene: erbb2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.365 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 40329538; 33720042
Deafness_IsolatedAndComplex v1.365 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623) to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Deafness_IsolatedAndComplex v1.365 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v1.196 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623) to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Hereditary Neuropathy v1.195 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 40329538; 33720042
Deafness_IsolatedAndComplex v1.364 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.364 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Hereditary Neuropathy v1.195 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.364 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.364 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.29 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Deafness_IsolatedAndComplex v1.363 ERBB2 Chirag Patel Marked gene: ERBB2 as ready
Deafness_IsolatedAndComplex v1.363 ERBB2 Chirag Patel Gene: erbb2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v1.194 ERBB2 Chirag Patel Marked gene: ERBB2 as ready
Hereditary Neuropathy v1.194 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Hereditary Neuropathy v1.194 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Hereditary Neuropathy v1.194 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.29 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Hirschsprung disease v0.31 ERBB2 Chirag Patel Marked gene: ERBB2 as ready
Hirschsprung disease v0.31 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.29 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 33497358
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.31 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.30 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623) to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.30 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 40329538; 33720042
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.30 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.30 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Hirschsprung disease v0.30 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.28 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598 to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.27 ERBB3 Chirag Patel Publications for gene: ERBB3 were set to 17701904; 31752936; 33497358
Arthrogryposis v1.27 ERBB3 Chirag Patel Publications for gene: ERBB3 were set to 17701904; 31752936
Arthrogryposis v1.26 ERBB3 Chirag Patel reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33497358; Phenotypes: Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.26 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Arthrogryposis v1.26 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.25 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.25 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.24 Chirag Patel Added reviews for gene ERBB3 from panel Hereditary Neuropathy
Arthrogryposis v1.23 ERBB3 Chirag Patel Classified gene: ERBB3 as Green List (high evidence)
Arthrogryposis v1.23 ERBB3 Chirag Patel Gene: erbb3 has been classified as Green List (High Evidence).
Arthrogryposis v1.23 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623) to Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy
Arthrogryposis v1.22 ERBB2 Chirag Patel Publications for gene: ERBB2 were set to 40329538; 33720042
Arthrogryposis v1.22 ERBB2 Chirag Patel Mode of inheritance for gene: ERBB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.22 ERBB2 Chirag Patel Marked gene: ERBB2 as ready
Arthrogryposis v1.22 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.22 ERBB2 Chirag Patel Classified gene: ERBB2 as Red List (low evidence)
Arthrogryposis v1.22 ERBB2 Chirag Patel Gene: erbb2 has been classified as Red List (Low Evidence).
Arthrogryposis v1.21 ERBB2 Chirag Patel changed review comment from: Main paper for cases described in PMID 33720042.
2 siblings from consanguineous Turkish family with intestinal dysmotility, severe constipation (aganglionosis in submucosa at rectum), peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, sensorineural hearing loss, and clubfeet. They had a homozygous rare missense variant in ERBB2 gene (A710V) and parents were heterozygous carriers. No functional studies; to: Main paper for cases described in PMID 33720042.
2 siblings from consanguineous Turkish family with intestinal dysmotility, severe constipation (aganglionosis in submucosa at rectum), peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, sensorineural hearing loss, and clubfeet. They had a homozygous rare missense variant in ERBB2 gene (A710V) and parents were heterozygous carriers. Western blot analysis revealed a drastic decrease of both ERBB2 and ERBB3 phosphorylation. Other papers showed mice knockout of Erbb2 results in the absence or severe depletion of various neural crest–derived cells.
Mendeliome v1.4902 ERBB2 Chirag Patel changed review comment from: Main paper for cases described in PMID 33720042.
2 siblings from consanguineous Turkish family with intestinal dysmotility, severe constipation (aganglionosis in submucosa at rectum), peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, sensorineural hearing loss, and clubfeet. They had a homozygous rare missense variant in ERBB2 gene (A710V) and parents were heterozygous carriers. No functional studies; to: Main paper for cases described in PMID 33720042.
2 siblings from consanguineous Turkish family with intestinal dysmotility, severe constipation (aganglionosis in submucosa at rectum), peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, sensorineural hearing loss, and clubfeet. They had a homozygous rare missense variant in ERBB2 gene (A710V) and parents were heterozygous carriers. Western blot analysis revealed a drastic decrease of both ERBB2 and ERBB3 phosphorylation. Other papers showed mice knockout of Erbb2 results in the absence or severe depletion of various neural crest–derived cells.
Arthrogryposis v1.21 ERBB3 Chirag Patel Classified gene: ERBB3 as Green List (high evidence)
Arthrogryposis v1.21 ERBB3 Chirag Patel Gene: erbb3 has been classified as Green List (High Evidence).
Arthrogryposis v1.21 ERBB3 Chirag Patel Classified gene: ERBB3 as Green List (high evidence)
Arthrogryposis v1.21 ERBB3 Chirag Patel Gene: erbb3 has been classified as Green List (High Evidence).
Hirschsprung disease v0.29 Chirag Patel Copied gene ERBB2 from panel Mendeliome
Hirschsprung disease v0.29 ERBB2 Chirag Patel gene: ERBB2 was added
gene: ERBB2 was added to Hirschsprung disease. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Hereditary Neuropathy v1.193 Chirag Patel Copied gene ERBB2 from panel Mendeliome
Hereditary Neuropathy v1.193 ERBB2 Chirag Patel gene: ERBB2 was added
gene: ERBB2 was added to Hereditary Neuropathy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Gastrointestinal neuromuscular disease v1.27 Chirag Patel Copied gene ERBB2 from panel Mendeliome
Gastrointestinal neuromuscular disease v1.27 ERBB2 Chirag Patel gene: ERBB2 was added
gene: ERBB2 was added to Gastrointestinal neuromuscular disease. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Deafness_IsolatedAndComplex v1.363 Chirag Patel Copied gene ERBB2 from panel Mendeliome
Deafness_IsolatedAndComplex v1.363 ERBB2 Chirag Patel gene: ERBB2 was added
gene: ERBB2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Mendeliome v1.4902 MACF1 Lucy Spencer changed review comment from: Biallelic disease

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.

Neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant; to: Biallelic disease

Myasthenic syndrome AMBER:
PMID: 30842214 Oury 2019 1 patient with myasthenic syndrome (ptosis, weakness of extraocular muscles and neck flexors and difficulty swallowing, onset in childhood chet missense p.Leu2208Phe p.Thr1799Ala (in MANE select Leu3768Phe Thr3359Ala). A 2nd patient with mild adult onset limb girdle myasthenic syndrome, homozygous for p.Val1563Met (in MANE select: Val3123Met) also reported in PMID: 37721175 Polavarapu 2024.

Neurodevelopmental disorder GREEN:
PMID: 40925378; Dekker 2025- biallelic patients with a neurodevelopmental disorder. 9 unrelated patients across the main paper and supplementary data, all but 1 have homozygous or compound heterozygous missense spread across the gene, 1 has a homozygous nonsense. All have some degree of ID or developmental delay with variable additional features including microcephaly, hypotonia, muscle weakness, ataxia, or hypomyelination. The majority of their variants are in the plankin domain which is very large p.583-1533, however this is a mix of both recessive and dominant variants. Almost all of the missense are rare in gnomad however one p.Leu1349Met has over 1000 hets and 2 homs.

Also in this papers supplementary data is a review of other biallelic cases in the literature. all but 1 have compound het missense scattered across the gene
PMID: 24476948 1 with fetal akinesia
PMID: 32010038 1 with spastic tetraplegia, dystonia, joint contracture, feeding difficulty and dev delay
PMID: 33600046 3 patients; proximal and distal limb atrophy and weakness in one, axonal polyneuropathy with exotropia in another, and infantile muscular atrophy and weakness in the 3rd.
PMID: 29667327 1 with West syndrome
PMID: 297066461 with corpus callosum hypoplasia. this individual has a chet missense and NMD variant
Arthrogryposis v1.21 Chirag Patel Copied gene ERBB2 from panel Mendeliome
Arthrogryposis v1.21 ERBB2 Chirag Patel gene: ERBB2 was added
gene: ERBB2 was added to Arthrogryposis. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERBB2 were set to 40329538; 33720042
Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Hereditary Neuropathy v1.192 ERBB3 Chirag Patel Marked gene: ERBB3 as ready
Hereditary Neuropathy v1.192 ERBB3 Chirag Patel Gene: erbb3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.192 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hereditary Neuropathy v1.192 ERBB3 Chirag Patel Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Arthrogryposis v1.20 Chirag Patel Added reviews for gene ERBB3 from panel Gastrointestinal neuromuscular disease
Hereditary Neuropathy v1.191 Chirag Patel Copied gene ERBB3 from panel Mendeliome
Hereditary Neuropathy v1.191 ERBB3 Chirag Patel gene: ERBB3 was added
gene: ERBB3 was added to Hereditary Neuropathy. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERBB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERBB3 were set to 17701904; 31752936; 33720042; 33497358
Phenotypes for gene: ERBB3 were set to Lethal congenital contractural syndrome 2, MIM# 607598; Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v1.4902 MACF1 Lucy Spencer reviewed gene: MACF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30842214, 37721175, 40925378, 33600046, 24476948, 32010038, 29667327, 297066461; Phenotypes: Congenital myasthenic syndrome, MONDO:0018940, MACF1-related, Neurodevelopmental disorder (MONDO:0700092), MACF1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4902 ERBB2 Chirag Patel reviewed gene: ERBB2: Rating: RED; Mode of pathogenicity: None; Publications: 33497358; Phenotypes: Visceral neuropathy, familial, 2, autosomal recessive, MIM # 619465, Complex neurocristinopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4902 ERBB2 Chirag Patel Phenotypes for gene: ERBB2 were changed from Visceral neuropathy, familial, 2, autosomal recessive, MIM# 619465; Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453 to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453; Hirschsprung disease (HSCR, aganglionic megacolon, MIM#142623)
Mendeliome v1.4901 ATP11C Chirag Patel Publications for gene: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472; 37314652
Mendeliome v1.4900 ATP11C Chirag Patel Phenotypes for gene: ATP11C were changed from X-linked congenital hemolytic anemia, MONDO:0060455 to X-linked congenital hemolytic anemia, MONDO:0060455
Mendeliome v1.4899 ATP11C Chirag Patel Phenotypes for gene: ATP11C were changed from X-linked congenital hemolytic anemia, MONDO:0060455 to X-linked congenital hemolytic anemia, MONDO:0060455
Mendeliome v1.4900 ATP11C Chirag Patel Phenotypes for gene: ATP11C were changed from Hemolytic anemia, congenital, X-linked MIM#301015 to X-linked congenital hemolytic anemia, MONDO:0060455
Mendeliome v1.4899 ATP11C Chirag Patel Classified gene: ATP11C as Green List (high evidence)
Mendeliome v1.4899 ATP11C Chirag Patel Gene: atp11c has been classified as Green List (High Evidence).
Mendeliome v1.4898 ATP11C Chirag Patel Marked gene: ATP11C as ready
Mendeliome v1.4898 ATP11C Chirag Patel Gene: atp11c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4898 Chirag Patel Added reviews for gene ATP11C from panel Red cell disorders
Red cell disorders v1.61 ATP11C Chirag Patel Marked gene: ATP11C as ready
Red cell disorders v1.61 ATP11C Chirag Patel Gene: atp11c has been classified as Green List (High Evidence).
Red cell disorders v1.61 ATP11C Chirag Patel Phenotypes for gene: ATP11C were changed from X-linked congenital hemolytic anemia, MONDO:0060455 to X-linked congenital hemolytic anemia, MONDO:0060455
Red cell disorders v1.60 ATP11C Chirag Patel Phenotypes for gene: ATP11C were changed from Hemolytic anemia, congenital, X-linked MIM#301015 to X-linked congenital hemolytic anemia, MONDO:0060455
Red cell disorders v1.59 ATP11C Chirag Patel Publications for gene: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Red cell disorders v1.58 ATP11C Chirag Patel Classified gene: ATP11C as Green List (high evidence)
Red cell disorders v1.58 ATP11C Chirag Patel Gene: atp11c has been classified as Green List (High Evidence).
Red cell disorders v1.57 ATP11C Chirag Patel reviewed gene: ATP11C: Rating: GREEN; Mode of pathogenicity: None; Publications: 42018644; Phenotypes: X-linked congenital hemolytic anemia, MONDO:0060455; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Dystonia and Chorea v0.348 SRRM4 Chirag Patel Marked gene: SRRM4 as ready
Dystonia and Chorea v0.348 SRRM4 Chirag Patel Gene: srrm4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.800 SRRM4 Chirag Patel Marked gene: SRRM4 as ready
Intellectual disability syndromic and non-syndromic v1.800 SRRM4 Chirag Patel Gene: srrm4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.416 SRRM4 Chirag Patel Marked gene: SRRM4 as ready
Genetic Epilepsy v1.416 SRRM4 Chirag Patel Gene: srrm4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.800 Chirag Patel Copied gene SRRM4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.800 SRRM4 Chirag Patel gene: SRRM4 was added
gene: SRRM4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SRRM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM4 were set to 41958152
Phenotypes for gene: SRRM4 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM4-related
Mode of pathogenicity for gene: SRRM4 was set to Other
Genetic Epilepsy v1.416 Chirag Patel Copied gene SRRM4 from panel Mendeliome
Genetic Epilepsy v1.416 SRRM4 Chirag Patel gene: SRRM4 was added
gene: SRRM4 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SRRM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM4 were set to 41958152
Phenotypes for gene: SRRM4 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM4-related
Mode of pathogenicity for gene: SRRM4 was set to Other
Dystonia and Chorea v0.348 Chirag Patel Copied gene SRRM4 from panel Mendeliome
Dystonia and Chorea v0.348 SRRM4 Chirag Patel gene: SRRM4 was added
gene: SRRM4 was added to Dystonia and Chorea. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SRRM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM4 were set to 41958152
Phenotypes for gene: SRRM4 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM4-related
Mode of pathogenicity for gene: SRRM4 was set to Other
Mendeliome v1.4897 SRRM4 Chirag Patel Classified gene: SRRM4 as Green List (high evidence)
Mendeliome v1.4897 SRRM4 Chirag Patel Gene: srrm4 has been classified as Green List (High Evidence).
Mendeliome v1.4896 SRRM4 Chirag Patel Classified gene: SRRM4 as Green List (high evidence)
Mendeliome v1.4896 SRRM4 Chirag Patel Gene: srrm4 has been classified as Green List (High Evidence).
Mendeliome v1.4895 SRRM4 Chirag Patel Marked gene: SRRM4 as ready
Mendeliome v1.4895 SRRM4 Chirag Patel Gene: srrm4 has been classified as Red List (Low Evidence).
Mendeliome v1.4895 SRRM4 Chirag Patel changed review comment from: 3 unrelated individuals with developmental delay, absent speech, intellectual impairment, epilepsy, early‑onset dystonia and chorea (6mths-20mths). Trio WES/WGS identified a de novo canonical splice‑donor variant in SRRM4 in each individual (c.464+2T>C or c.464+2T>A). SRRM4 is an exclusively neural-expressed splicing-factor gene. RNA-sequencing in patient fibroblasts revealed 2 variant-specific mutant SRRM4-mRNA isoforms (1 x isoform lacking exon 5, and 1 x isoform containing a 69-nucleotide elongation of exon 5) suggestive of a mechanism other than loss-of-function. Additionally, they uncovered altered splicing patterns of known SRRM4 downstream mRNA-substrates in patient cells compared to SRRM4 expression-activated control fibroblasts.
Sources: Literature; to: 3 unrelated individuals with developmental delay, absent speech, intellectual impairment, epilepsy, early‑onset dystonia and chorea (6mths-20mths). Trio WES/WGS identified a rare de novo canonical splice‑donor variant in SRRM4 in each individual (c.464+2T>C or c.464+2T>A). SRRM4 is an exclusively neural-expressed splicing-factor gene. RNA-sequencing in patient fibroblasts revealed 2 variant-specific mutant SRRM4-mRNA isoforms (1 x isoform lacking exon 5, and 1 x isoform containing a 69-nucleotide elongation of exon 5) suggestive of a mechanism other than loss-of-function. Additionally, they uncovered altered splicing patterns of known SRRM4 downstream mRNA-substrates in patient cells compared to SRRM4 expression-activated control fibroblasts.
Sources: Literature
Mendeliome v1.4895 SRRM4 Chirag Patel gene: SRRM4 was added
gene: SRRM4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SRRM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM4 were set to 41958152
Phenotypes for gene: SRRM4 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM4-related
Mode of pathogenicity for gene: SRRM4 was set to Other
Review for gene: SRRM4 was set to GREEN
Added comment: 3 unrelated individuals with developmental delay, absent speech, intellectual impairment, epilepsy, early‑onset dystonia and chorea (6mths-20mths). Trio WES/WGS identified a de novo canonical splice‑donor variant in SRRM4 in each individual (c.464+2T>C or c.464+2T>A). SRRM4 is an exclusively neural-expressed splicing-factor gene. RNA-sequencing in patient fibroblasts revealed 2 variant-specific mutant SRRM4-mRNA isoforms (1 x isoform lacking exon 5, and 1 x isoform containing a 69-nucleotide elongation of exon 5) suggestive of a mechanism other than loss-of-function. Additionally, they uncovered altered splicing patterns of known SRRM4 downstream mRNA-substrates in patient cells compared to SRRM4 expression-activated control fibroblasts.
Sources: Literature
Retinitis pigmentosa v0.247 CFAP20 Zornitza Stark Phenotypes for gene: CFAP20 were changed from Retinitis pigmentosa (MONDO:0019200), CFAP20-related to Retinitis pigmentosa 107, MIM# 621587
Retinitis pigmentosa v0.246 CFAP20 Zornitza Stark reviewed gene: CFAP20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 107, MIM# 621587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4894 CFAP20 Zornitza Stark Phenotypes for gene: CFAP20 were changed from Retinitis pigmentosa (MONDO:0019200), CFAP20-related to Retinitis pigmentosa 107, MIM# 621587
Mendeliome v1.4893 CFAP20 Zornitza Stark reviewed gene: CFAP20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 107, MIM# 621587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.799 RPS4X Chirag Patel Marked gene: RPS4X as ready
Intellectual disability syndromic and non-syndromic v1.799 RPS4X Chirag Patel Gene: rps4x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.799 Chirag Patel Copied gene RPS4X from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.799 RPS4X Chirag Patel gene: RPS4X was added
gene: RPS4X was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RPS4X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: RPS4X were set to 42031741
Phenotypes for gene: RPS4X were set to Neurodevelopmental disorder, MONDO:0700092, RPS4X-related
Mendeliome v1.4893 RPS4X Chirag Patel Marked gene: RPS4X as ready
Mendeliome v1.4893 RPS4X Chirag Patel Gene: rps4x has been classified as Green List (High Evidence).
Mendeliome v1.4893 RPS4X Chirag Patel Classified gene: RPS4X as Green List (high evidence)
Mendeliome v1.4893 RPS4X Chirag Patel Gene: rps4x has been classified as Green List (High Evidence).
Mendeliome v1.4892 RPS4X Chirag Patel gene: RPS4X was added
gene: RPS4X was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS4X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: RPS4X were set to 42031741
Phenotypes for gene: RPS4X were set to Neurodevelopmental disorder, MONDO:0700092, RPS4X-related
Review for gene: RPS4X was set to GREEN
Added comment: PMID 42031741 reports 7 affected males from 6 unrelated families with neurodevelopmental disorder (developmental delay, developmental language disorder, intellectual disability, ASD, ADHD). There were 5 different rare variants identified (4 x missense, 1 frameshift variant), and all variants were all maternally inherited. Most were predicted to be deleterious.

Patient fibroblasts carrying the p.Arg221Gln variant showed ~30 % reduced RPS4X protein. Zebrafish rps4x morpholino knock‑down caused brain defects that were rescued by wild‑type mRNA but not by mutant mRNA. However, their ability to assign pathogenicity to the majority of variants was limited.
Sources: Literature
Dystonia and Chorea v0.347 DRD1 Chirag Patel Marked gene: DRD1 as ready
Dystonia and Chorea v0.347 DRD1 Chirag Patel Gene: drd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.798 DRD1 Chirag Patel Marked gene: DRD1 as ready
Intellectual disability syndromic and non-syndromic v1.798 DRD1 Chirag Patel Gene: drd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.798 Chirag Patel Copied gene DRD1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.798 DRD1 Chirag Patel gene: DRD1 was added
gene: DRD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: DRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRD1 were set to 41966088; 37048120
Phenotypes for gene: DRD1 were set to Neurodevelopmental disorder, MONDO:0700092, DRD1-related
Dystonia and Chorea v0.347 Chirag Patel Copied gene DRD1 from panel Mendeliome
Dystonia and Chorea v0.347 DRD1 Chirag Patel gene: DRD1 was added
gene: DRD1 was added to Dystonia and Chorea. Sources: Expert Review Green,Literature
Mode of inheritance for gene: DRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRD1 were set to 41966088; 37048120
Phenotypes for gene: DRD1 were set to Neurodevelopmental disorder, MONDO:0700092, DRD1-related
Mendeliome v1.4891 DRD1 Chirag Patel Marked gene: DRD1 as ready
Mendeliome v1.4891 DRD1 Chirag Patel Gene: drd1 has been classified as Green List (High Evidence).
Mendeliome v1.4891 DRD1 Chirag Patel Classified gene: DRD1 as Green List (high evidence)
Mendeliome v1.4891 DRD1 Chirag Patel Gene: drd1 has been classified as Green List (High Evidence).
Mendeliome v1.4890 DRD1 Chirag Patel gene: DRD1 was added
gene: DRD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRD1 were set to 41966088; 37048120
Phenotypes for gene: DRD1 were set to Neurodevelopmental disorder, MONDO:0700092, DRD1-related
Review for gene: DRD1 was set to GREEN
Added comment: PMID 41966088 and 37048120 reports 9 individuals from 4 unrelated consanguineous families with rare homozygous DRD1 missense variants (p.Thr37Met, p.Asp103Asn, p.Tyr37Lys). The clinical presentation was infantile‑onset generalized dystonia, axial hypotonia and severe neurodevelopmental impairment. Parents were heterozygous carriers in each family. Variant‑specific live‑cell functional assays demonstrate loss‑of‑function and partial rescue, supporting pathogenicity.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.797 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MONDO:0014484 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Intellectual disability syndromic and non-syndromic v1.799 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MONDO:0014484 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Intellectual disability syndromic and non-syndromic v1.799 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MONDO:0014484 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Intellectual disability syndromic and non-syndromic v1.798 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MIM#616080 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Intellectual disability syndromic and non-syndromic v1.798 CDK6 Chirag Patel Classified gene: CDK6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.798 CDK6 Chirag Patel Gene: cdk6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.798 CDK6 Chirag Patel Publications for gene: CDK6 were set to 23918663; 40801391; 41856556
Intellectual disability syndromic and non-syndromic v1.797 CDK6 Chirag Patel Publications for gene: CDK6 were set to 23918663; 40801391
Intellectual disability syndromic and non-syndromic v1.797 CDK6 Chirag Patel Classified gene: CDK6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.797 CDK6 Chirag Patel Gene: cdk6 has been classified as Green List (High Evidence).
Microcephaly v1.439 CDK6 Chirag Patel Classified gene: CDK6 as Green List (high evidence)
Microcephaly v1.439 CDK6 Chirag Patel Gene: cdk6 has been classified as Green List (High Evidence).
Microcephaly v1.438 CDK6 Chirag Patel Classified gene: CDK6 as Green List (high evidence)
Microcephaly v1.438 CDK6 Chirag Patel Gene: cdk6 has been classified as Green List (High Evidence).
Microcephaly v1.437 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MONDO:0014484 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Microcephaly v1.437 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MONDO:0014484 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Microcephaly v1.436 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MIM#616080 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Microcephaly v1.436 CDK6 Chirag Patel Publications for gene: CDK6 were set to 23918663; 40801391
Microcephaly v1.435 Chirag Patel Added reviews for gene CDK6 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.796 Chirag Patel Added reviews for gene CDK6 from panel Mendeliome
Mendeliome v1.4889 CDK6 Chirag Patel Phenotypes for gene: CDK6 were changed from Microcephaly 12, primary, autosomal recessive, MIM#616080 to Microcephaly 12, primary, autosomal recessive, MONDO:0014484
Mendeliome v1.4888 CDK6 Chirag Patel Publications for gene: CDK6 were set to 23918663; 40801391
Mendeliome v1.4887 CDK6 Chirag Patel Classified gene: CDK6 as Green List (high evidence)
Mendeliome v1.4887 CDK6 Chirag Patel Gene: cdk6 has been classified as Green List (High Evidence).
Mendeliome v1.4886 CDK6 Chirag Patel reviewed gene: CDK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 41856556; Phenotypes: Microcephaly 12, primary, autosomal recessive, MONDO:0014484; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4886 BMP10 Chirag Patel Phenotypes for gene: BMP10 were changed from Pulmonary arterial hypertension MONDO:0015924, BMP10-related to Pulmonary arterial hypertension MONDO:0015924, BMP10-related
Mendeliome v1.4885 BMP10 Chirag Patel Publications for gene: BMP10 were set to 30578383
Mendeliome v1.4885 BMP10 Chirag Patel Phenotypes for gene: BMP10 were changed from Pulmonary arterial hypertension MONDO:0015924, BMP10-related to Pulmonary arterial hypertension MONDO:0015924, BMP10-related
Mendeliome v1.4885 BMP10 Chirag Patel Phenotypes for gene: BMP10 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, BMP10-related
Mendeliome v1.4884 Chirag Patel Added reviews for gene BMP10 from panel Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension v1.59 BMP10 Chirag Patel reviewed gene: BMP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 41882294; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMP10-related; Mode of inheritance: None
Pulmonary Arterial Hypertension v1.59 BMP10 Chirag Patel Deleted their review
Pulmonary Arterial Hypertension v1.59 BMP10 Chirag Patel edited their review of gene: BMP10: Added comment: PMID 41882294 included one individual with CHD-associated PAH and a heterozygous frameshift variant in BMP10 (p.Asn321Lysfs*6). The variant is absent from gnomAD v4.1.0 but classified as VUS, and has no segregation information or functional experiments.; Changed rating: AMBER
Pulmonary Arterial Hypertension v1.59 BMP10 Chirag Patel reviewed gene: BMP10: Rating: RED; Mode of pathogenicity: None; Publications: 41882294; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMP10-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.795 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.793 PDS5B Chirag Patel Publications for gene: PDS5B were set to 41810376
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.795 PDS5B Chirag Patel Publications for gene: PDS5B were set to 41810376
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from 41810376 to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.794 PDS5B Chirag Patel Publications for gene: PDS5B were set to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.793 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from 41810376 to 41810376
Intellectual disability syndromic and non-syndromic v1.793 PDS5B Chirag Patel Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Intellectual disability syndromic and non-syndromic v1.793 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.793 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.793 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.793 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.792 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to 41810376
Intellectual disability syndromic and non-syndromic v1.792 PDS5B Chirag Patel Marked gene: PDS5B as ready
Intellectual disability syndromic and non-syndromic v1.792 PDS5B Chirag Patel Gene: pds5b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4883 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Mendeliome v1.4883 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.792 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.792 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.792 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092, PDS5B-related to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.792 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Intellectual disability syndromic and non-syndromic v1.791 PDS5B Chirag Patel Tag preprint was removed from gene: PDS5B.
Mendeliome v1.4882 PDS5B Chirag Patel Tag preprint was removed from gene: PDS5B.
Mendeliome v1.4882 PDS5B Chirag Patel Phenotypes for gene: PDS5B were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092, PDS5B-related
Mendeliome v1.4881 PDS5B Chirag Patel Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Intellectual disability syndromic and non-syndromic v1.791 PDS5A Chirag Patel Tag preprint was removed from gene: PDS5A.
Mendeliome v1.4880 PDS5A Chirag Patel Tag preprint was removed from gene: PDS5A.
Intellectual disability syndromic and non-syndromic v1.791 PDS5A Chirag Patel Classified gene: PDS5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.791 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v1.4880 PDS5A Chirag Patel Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690; 41810376
Intellectual disability syndromic and non-syndromic v1.790 PDS5A Chirag Patel Publications for gene: PDS5A were set to 30158690; 41810376
Intellectual disability syndromic and non-syndromic v1.790 PDS5A Chirag Patel Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Intellectual disability syndromic and non-syndromic v1.789 PDS5A Chirag Patel Phenotypes for gene: PDS5A were changed from complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related to complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related
Intellectual disability syndromic and non-syndromic v1.788 PDS5A Chirag Patel Phenotypes for gene: PDS5A were changed from complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related to complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related
Intellectual disability syndromic and non-syndromic v1.788 PDS5A Chirag Patel Phenotypes for gene: PDS5A were changed from Complex neurodevelopmental disorder, MONDO:0100038 to complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related
Mendeliome v1.4879 PDS5A Chirag Patel Phenotypes for gene: PDS5A were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Complex neurodevelopmental disorder, MONDO:0100038, PDS5A -related
Mendeliome v1.4878 PDS5A Chirag Patel Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Mendeliome v1.4877 PDS5A Chirag Patel Classified gene: PDS5A as Green List (high evidence)
Mendeliome v1.4877 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Rasopathy v0.114 Chirag Patel Added reviews for gene RASA2 from panel Mendeliome
Fetal anomalies v1.581 Chirag Patel Added reviews for gene RASA2 from panel Mendeliome
Mendeliome v1.4876 FBLN2 Chirag Patel changed review comment from: 2 unrelated individuals with idiopathic PAH from a large cohort with rare heterozygous missense (p.(Leu774Pro)) or splice (c.2842+1G>C) variant in FBLN2. The variants are located within the calcium-binding domain which could reduce
calcium binding affinity. No segregation studies or functional studies performed.; to: 2 unrelated individuals with idiopathic PAH from a large cohort with rare heterozygous missense (p.(Leu774Pro)) or splice (c.2842+1G>C) variant in FBLN2. The variants are located within the calcium-binding domain which could reduce calcium binding affinity. No segregation studies or functional studies performed.
Pulmonary Arterial Hypertension v1.59 FBLN2 Chirag Patel changed review comment from: 2 unrelated individuals with idiopathic PAH from a large cohort with rare heterozygous missense (p.(Leu774Pro)) or splice (c.2842+1G>C) variant in FBLN2. The variants are located within the calcium-binding domain which could reduce
calcium binding affinity. No segregation studies or functional studies performed.; to: 2 unrelated individuals with idiopathic PAH from a large cohort with rare heterozygous missense (p.(Leu774Pro)) or splice (c.2842+1G>C) variant in FBLN2. The variants are located within the calcium-binding domain which could reduce calcium binding affinity. No segregation studies or functional studies performed.
Pulmonary Arterial Hypertension v1.59 Chirag Patel Added reviews for gene FBLN2 from panel Mendeliome
Mendeliome v1.4876 FBLN2 Chirag Patel reviewed gene: FBLN2: Rating: RED; Mode of pathogenicity: None; Publications: 41882294; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, FBLN2-related; Mode of inheritance: None
Mendeliome v1.4876 PTCHD3 Chirag Patel Marked gene: PTCHD3 as ready
Mendeliome v1.4876 PTCHD3 Chirag Patel Gene: ptchd3 has been classified as Red List (Low Evidence).
Mendeliome v1.4876 PTCHD3 Chirag Patel Phenotypes for gene: PTCHD3 were changed from Syndromic disease, MONDO:0002254 to Nevoid basal cell carcinoma syndrome, MONDO:0007187
Mendeliome v1.4875 PTCHD3 Chirag Patel gene: PTCHD3 was added
gene: PTCHD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTCHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTCHD3 were set to 41848310
Phenotypes for gene: PTCHD3 were set to Syndromic disease, MONDO:0002254
Review for gene: PTCHD3 was set to RED
Added comment: 2 individuals from 1 unrelated family (father-daughter) with a monoallelic variant in PTCHD3 presenting with Basal Cell Nevus Syndrome (BCNS). Clinical features include multiple odontogenic keratocysts, facial pigmented nevi, hypertelorism, and frontal-parietal bone protrusion. The authors propose the variant activates the Hedgehog pathway, supported by molecular docking simulations and increased expression of matrix metalloproteinases in patient-derived fibroblasts.
Sources: Literature
Ataxia v1.205 NEFM Chirag Patel Marked gene: NEFM as ready
Ataxia v1.205 NEFM Chirag Patel Gene: nefm has been classified as Red List (Low Evidence).
Ataxia v1.205 Chirag Patel Copied gene NEFM from panel Mendeliome
Ataxia v1.205 NEFM Chirag Patel gene: NEFM was added
gene: NEFM was added to Ataxia. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEFM were set to 41913087
Phenotypes for gene: NEFM were set to Cerebellar ataxia, MONDO:0000437
Mendeliome v1.4874 NEFM Chirag Patel Marked gene: NEFM as ready
Mendeliome v1.4874 NEFM Chirag Patel Gene: nefm has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.787 MDGA1 Chirag Patel Marked gene: MDGA1 as ready
Intellectual disability syndromic and non-syndromic v1.787 MDGA1 Chirag Patel Gene: mdga1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4874 NEFM Chirag Patel gene: NEFM was added
gene: NEFM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEFM were set to 41913087
Phenotypes for gene: NEFM were set to Cerebellar ataxia, MONDO:0000437
Review for gene: NEFM was set to RED
Added comment: 2 individuals from 1 family with compound heterozygous rare missense variants in NEFM, which encodes for a neurofilament protein. They presented with pure cerebellar ataxia (post-puberty onset of dysmetria of upper and lower limbs, speech ataxia, wide-based stance, and gait oscillations). The variants segregated within the family. Evidence is supported by in silico analysis predicting dysregulation of phosphorylation sites, though experimental functional validation of the patient variants was not performed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.787 Chirag Patel Copied gene MDGA1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.787 MDGA1 Chirag Patel gene: MDGA1 was added
gene: MDGA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MDGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA1 were set to 41862769; 40585099
Phenotypes for gene: MDGA1 were set to Neurodevelopmental disorder, MONDO:0700092, MDGA1-related
Mendeliome v1.4873 MDGA1 Chirag Patel Classified gene: MDGA1 as Amber List (moderate evidence)
Mendeliome v1.4873 MDGA1 Chirag Patel Gene: mdga1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4873 MDGA1 Chirag Patel Classified gene: MDGA1 as Amber List (moderate evidence)
Mendeliome v1.4873 MDGA1 Chirag Patel Gene: mdga1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4873 MDGA1 Chirag Patel Classified gene: MDGA1 as Amber List (moderate evidence)
Mendeliome v1.4873 MDGA1 Chirag Patel Gene: mdga1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4872 MDGA1 Chirag Patel Classified gene: MDGA1 as Amber List (moderate evidence)
Mendeliome v1.4872 MDGA1 Chirag Patel Gene: mdga1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4871 MDGA1 Chirag Patel Marked gene: MDGA1 as ready
Mendeliome v1.4871 MDGA1 Chirag Patel Gene: mdga1 has been classified as Red List (Low Evidence).
Mendeliome v1.4871 MDGA1 Chirag Patel gene: MDGA1 was added
gene: MDGA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA1 were set to 41862769; 40585099
Phenotypes for gene: MDGA1 were set to Neurodevelopmental disorder, MONDO:0700092, MDGA1-related
Review for gene: MDGA1 was set to AMBER
gene: MDGA1 was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated families with biallelic missense variants in MDGA1 presenting with autism spectrum disorder, intellectual disability, and mild dysmorphic features. Functional assays in human hippocampal neurons demonstrate that the variants disrupt the triangular extracellular structure of the protein and cause loss-of-function in the negative regulation of GABAergic synapses. Additionally, Mdga1 male knock-in (KI) and conditional male knockout (cKO) mouse models recapitulate social and communicative deficits, with behavioral and electrophysiological deficits in male KI mice being rescued by Bazedoxifene. No behavioral deficits were seen in female counterparts. But authors state that extensive future validation in larger human cohorts, including functional studies of patient-derived cells, is needed to establish utility as a reliable diagnostic biomarker.
Sources: Literature
Amelogenesis imperfecta v1.16 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Amelogenesis imperfecta v1.16 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.15 SUPT4H1 Chirag Patel Marked gene: SUPT4H1 as ready
Amelogenesis imperfecta v1.15 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Mendeliome v1.4870 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Mendeliome v1.4870 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Mendeliome v1.4869 SUPT4H1 Chirag Patel Marked gene: SUPT4H1 as ready
Mendeliome v1.4869 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.786 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.415 ATG12 Chirag Patel Marked gene: ATG12 as ready
Genetic Epilepsy v1.415 ATG12 Chirag Patel Gene: atg12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.785 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.785 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.101 ATG12 Chirag Patel Marked gene: ATG12 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.101 ATG12 Chirag Patel Gene: atg12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.785 SUPT4H1 Chirag Patel Classified gene: SUPT4H1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.785 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.784 SUPT4H1 Chirag Patel Marked gene: SUPT4H1 as ready
Intellectual disability syndromic and non-syndromic v1.784 SUPT4H1 Chirag Patel Gene: supt4h1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.415 Chirag Patel Copied gene ATG12 from panel Mendeliome
Genetic Epilepsy v1.415 ATG12 Chirag Patel gene: ATG12 was added
gene: ATG12 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092
Cerebellar and Pontocerebellar Hypoplasia v1.101 Chirag Patel Copied gene ATG12 from panel Mendeliome
Cerebellar and Pontocerebellar Hypoplasia v1.101 ATG12 Chirag Patel gene: ATG12 was added
gene: ATG12 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092
Fetal anomalies v1.580 TNXB Zornitza Stark Phenotypes for gene: TNXB were changed from Vesicoureteral reflux 8 615963; Ehlers-Danlos syndrome due to tenascin X deficiency 606408 to Vesicoureteral reflux 8 615963
Fetal anomalies v1.579 TNXB Zornitza Stark Publications for gene: TNXB were set to 19921645; 28306229; 28306225; 23620400
Fetal anomalies v1.578 TNXB Zornitza Stark Classified gene: TNXB as Amber List (moderate evidence)
Fetal anomalies v1.578 TNXB Zornitza Stark Gene: tnxb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.577 TNXB Zornitza Stark edited their review of gene: TNXB: Added comment: PMID 26408188: 6 additional individuals from 3 families with rare missense variants. De novo in one family. PMID 34059960: 3 unrelated individuals, two with LoF variants, one with missense, identified in a large cohort. PMID 36995132: five individuals, again from a large cohort presenting with obstructive uropathy, three with LoF variant and one with missense; 5th individual compound het for LoF variants.

PMID 38370350: single compound het individual reported.

MODERATE by ClinGen. Lack of segregation and other experimental data to support association, most of the data comes from observations in large cohorts of individuals with VUR/obstructive uropathy.; Changed rating: AMBER; Changed publications: 26408188, 34059960, 36995132, 38370350
Mendeliome v1.4869 TNXB Zornitza Stark Phenotypes for gene: TNXB were changed from Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408 to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408; Vesicoureteral reflux 8, MIM# 615963
Mendeliome v1.4868 TNXB Zornitza Stark Publications for gene: TNXB were set to 28306229; 28306225; 23620400
Mendeliome v1.4867 TNXB Zornitza Stark Mode of inheritance for gene: TNXB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4866 TNXB Zornitza Stark changed review comment from: Association with VUR:

PMID 26408188: 6 additional individuals from 3 families with rare missense variants. De novo in one family. PMID 34059960: 3 unrelated individuals, two with LoF variants, one with missense, identified in a large cohort. PMID 36995132: five individuals, again from a large cohort presenting with obstructive uropathy, three with LoF variant and one with missense; 5th individual compound het for LoF variants.

PMID 38370350: single compound het individual reported.

MODERATE by ClinGen. Lack of segregation and other experimental data to support association, most of the data comes from observations in large cohorts of individuals with VUR/obstructive uropathy.; to: Association with VUR:

PMID 26408188: 6 additional individuals from 3 families with rare missense variants. De novo in one family. PMID 34059960: 3 unrelated individuals, two with LoF variants, one with missense, identified in a large cohort. PMID 36995132: five individuals, again from a large cohort presenting with obstructive uropathy, three with LoF variant and one with missense; 5th individual compound het for LoF variants.

PMID 38370350: single compound het individual reported.

MODERATE by ClinGen. Lack of segregation and other experimental data to support association, most of the data comes from observations in large cohorts of individuals with VUR/obstructive uropathy.

AMBER for this association.
Mendeliome v1.4866 TNXB Zornitza Stark edited their review of gene: TNXB: Added comment: Association with VUR:

PMID 26408188: 6 additional individuals from 3 families with rare missense variants. De novo in one family. PMID 34059960: 3 unrelated individuals, two with LoF variants, one with missense, identified in a large cohort. PMID 36995132: five individuals, again from a large cohort presenting with obstructive uropathy, three with LoF variant and one with missense; 5th individual compound het for LoF variants.

PMID 38370350: single compound het individual reported.

MODERATE by ClinGen. Lack of segregation and other experimental data to support association, most of the data comes from observations in large cohorts of individuals with VUR/obstructive uropathy.; Changed publications: 28306229, 28306225, 23620400, 26408188, 34059960, 38370350, 36995132; Changed phenotypes: Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408, Vesicoureteral reflux 8, MIM# 615963; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.209 TNXB Zornitza Stark Marked gene: TNXB as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.209 TNXB Zornitza Stark Gene: tnxb has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.209 TNXB Zornitza Stark Publications for gene: TNXB were set to 23620400
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.208 TNXB Zornitza Stark Classified gene: TNXB as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.208 TNXB Zornitza Stark Gene: tnxb has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.207 TNXB Zornitza Stark edited their review of gene: TNXB: Added comment: PMID 26408188: 6 additional individuals from 3 families with rare missense variants. De novo in one family. PMID 34059960: 3 unrelated individuals, two with LoF variants, one with missense, identified in a large cohort. PMID 36995132: five individuals, again from a large cohort presenting with obstructive uropathy, three with LoF variant and one with missense; 5th individual compound het for LoF variants.

PMID 38370350: single compound het individual reported.

MODERATE by ClinGen. Lack of segregation and other experimental data to support association, most of the data comes from observations in large cohorts of individuals with VUR/obstructive uropathy.; Changed rating: AMBER; Changed publications: 23620400, 26408188, 34059960, 38370350, 36995132
Combined Immunodeficiency v1.148 B2M Zornitza Stark Classified gene: B2M as Amber List (moderate evidence)
Combined Immunodeficiency v1.148 B2M Zornitza Stark Gene: b2m has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.147 B2M Zornitza Stark reviewed gene: B2M: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 43 MIM# 241600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Amyloidosis v1.2 B2M Zornitza Stark Marked gene: B2M as ready
Amyloidosis v1.2 B2M Zornitza Stark Gene: b2m has been classified as Amber List (Moderate Evidence).
Amyloidosis v1.2 B2M Zornitza Stark Classified gene: B2M as Amber List (moderate evidence)
Amyloidosis v1.2 B2M Zornitza Stark Gene: b2m has been classified as Amber List (Moderate Evidence).
Amyloidosis v1.1 B2M Zornitza Stark Deleted their comment
Amyloidosis v1.1 B2M Zornitza Stark edited their review of gene: B2M: Added comment: LIMITED by ClinGen. Two multiplex families reported with missense variants, some functional and segregation data to support pathogenicity. PMID 37223323 reports additional proband but with same variant as in one of the previously reported families and no further supporting information; unclear if related or potentially founder variant.; Changed rating: AMBER; Changed publications: 35575118, 22693999, 37223323; Changed phenotypes: Amyloidosis, hereditary systemic 6, MIM# 620659; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4866 B2M Zornitza Stark Classified gene: B2M as Amber List (moderate evidence)
Mendeliome v1.4866 B2M Zornitza Stark Gene: b2m has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4865 B2M Zornitza Stark edited their review of gene: B2M: Added comment: Both associations are LIMITED by ClinGen. The recessive association has had limited replication over time, which is concerning, downgrade to Amber.; Changed rating: AMBER
Mendeliome v1.4865 ASTN2 Lucy Spencer reviewed gene: ASTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28940097, 34412080, 24381304, 32094338, 38674362; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, ASTN2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v1.12 Sarah Milton Copied Region FOXF1 upstream regulatory region from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.12 FOXF1 upstream regulatory region Sarah Milton Region: FOXF1 upstream regulatory region was added
Region: FOXF1 upstream regulatory region was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: FOXF1 upstream regulatory region.
Mode of inheritance for Region: FOXF1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: FOXF1 upstream regulatory region were set to PMID: 27822317, 27071622, 23034409, 24842713
Phenotypes for Region: FOXF1 upstream regulatory region were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
Intellectual disability syndromic and non-syndromic v1.784 ISCA-37448-Loss Sarah Milton Classified Region: ISCA-37448-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.784 ISCA-37448-Loss Sarah Milton Region: isca-37448-loss has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.157 ISCA-37494-Loss Sarah Milton Classified Region: ISCA-37494-Loss as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.157 ISCA-37494-Loss Sarah Milton Region: isca-37494-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.783 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.783 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.782 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.362 Sarah Milton Copied Region POU3F4 upstream regulatory region from panel Mendeliome
Deafness_IsolatedAndComplex v1.362 POU3F4 upstream regulatory region Sarah Milton Region: POU3F4 upstream regulatory region was added
Region: POU3F4 upstream regulatory region was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: POU3F4 upstream regulatory region.
Mode of inheritance for Region: POU3F4 upstream regulatory region was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: POU3F4 upstream regulatory region were set to PMID: 41170199, 35189936, 33860785
Phenotypes for Region: POU3F4 upstream regulatory region were set to Deafness, X-linked 2 MIM#304400
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.781 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.164 ISCA-46302-Gain Sarah Milton Classified Region: ISCA-46302-Gain as Green List (high evidence)
Common deletion and duplication syndromes v0.164 ISCA-46302-Gain Sarah Milton Region: isca-46302-gain has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.163 ISCA-46300-Loss Sarah Milton Classified Region: ISCA-46300-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.163 ISCA-46300-Loss Sarah Milton Region: isca-46300-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.162 ISCA-46296-Loss Sarah Milton Classified Region: ISCA-46296-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.162 ISCA-46296-Loss Sarah Milton Region: isca-46296-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.161 ISCA-37498-Loss Sarah Milton Classified Region: ISCA-37498-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.161 ISCA-37498-Loss Sarah Milton Region: isca-37498-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.160 ISCA-37494-Loss Sarah Milton Classified Region: ISCA-37494-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.160 ISCA-37494-Loss Sarah Milton Region: isca-37494-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.159 ISCA-37448-Loss Sarah Milton Classified Region: ISCA-37448-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.159 ISCA-37448-Loss Sarah Milton Region: isca-37448-loss has been classified as Green List (High Evidence).
Differences of Sex Development v1.56 SOX9 upstream regulatory region gain Sarah Milton Classified Region: SOX9 upstream regulatory region gain as Green List (high evidence)
Differences of Sex Development v1.56 SOX9 upstream regulatory region gain Sarah Milton Region: sox9 upstream regulatory region gain has been classified as Green List (High Evidence).
Mendeliome v1.4865 SOX9 upstream regulatory region gain Sarah Milton Classified Region: SOX9 upstream regulatory region gain as Green List (high evidence)
Mendeliome v1.4865 SOX9 upstream regulatory region gain Sarah Milton Region: sox9 upstream regulatory region gain has been classified as Green List (High Evidence).
Skeletal dysplasia v0.449 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Skeletal dysplasia v0.449 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.23 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Radial Ray Abnormalities v1.23 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Growth failure v1.108 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Growth failure v1.108 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4864 SHOX downstream regulatory region Sarah Milton Classified Region: SHOX downstream regulatory region as Green List (high evidence)
Mendeliome v1.4864 SHOX downstream regulatory region Sarah Milton Region: shox downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Classified Region: POU3F4 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Added comment: Comment on list classification: Well established with specific temporal bone findings
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Region: pou3f4 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Classified Region: POU3F4 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Added comment: Comment on list classification: Well established with specific temporal bone findings
Mendeliome v1.4863 POU3F4 upstream regulatory region Sarah Milton Region: pou3f4 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4862 POU3F4 upstream regulatory region Sarah Milton changed review comment from: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however functional studies have not been performed to demonstrate this as of yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature; to: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness - mixed conductive and sensorineural. A typical temporal bone deformity is often seen that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however this has not been clearly demonstrated yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Glaucoma congenital v1.13 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4862 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4862 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.22 PITX2 upstream regulatory region Sarah Milton Classified Region: PITX2 upstream regulatory region as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.22 PITX2 upstream regulatory region Sarah Milton Region: pitx2 upstream regulatory region has been classified as Green List (High Evidence).
Skeletal dysplasia v0.448 Sarah Milton Copied Region PITX1 upstream regulatory region from panel Mendeliome
Skeletal dysplasia v0.448 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: PITX1 upstream regulatory region.
Mode of inheritance for Region: PITX1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX1 upstream regulatory region were set to PMID: 30711920; 23022097; 25124102; 23587911
Phenotypes for Region: PITX1 upstream regulatory region were set to Liebenberg syndrome, MIM#186550
Hand and foot malformations v0.93 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.93 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4861 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4861 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4860 PITX1 upstream regulatory region Sarah Milton Classified Region: PITX1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4860 PITX1 upstream regulatory region Sarah Milton Region: pitx1 upstream regulatory region has been classified as Green List (High Evidence).
Regression v0.613 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Regression v0.613 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Regression v0.612 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Regression v0.612 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Ataxia v1.204 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Ataxia v1.204 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Leukodystrophy v0.395 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Leukodystrophy v0.395 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Mendeliome v1.4859 LMNB1 upstream region Sarah Milton Classified Region: LMNB1 upstream region as Green List (high evidence)
Mendeliome v1.4859 LMNB1 upstream region Sarah Milton Region: lmnb1 upstream region has been classified as Green List (High Evidence).
Craniosynostosis v1.86 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Craniosynostosis v1.86 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4858 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Mendeliome v1.4858 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Hand and foot malformations v0.92 IHH upstream regulatory region Sarah Milton Classified Region: IHH upstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.92 IHH upstream regulatory region Sarah Milton Region: ihh upstream regulatory region has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.58 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Pulmonary Arterial Hypertension v1.58 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4857 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4857 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4856 FOXF1 upstream regulatory region Sarah Milton Classified Region: FOXF1 upstream regulatory region as Green List (high evidence)
Mendeliome v1.4856 FOXF1 upstream regulatory region Sarah Milton Region: foxf1 upstream regulatory region has been classified as Green List (High Evidence).
Fetal anomalies v1.577 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Fetal anomalies v1.577 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Hand and foot malformations v0.91 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Hand and foot malformations v0.91 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4855 DLX5 downstream regulatory region Sarah Milton Classified Region: DLX5 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4855 DLX5 downstream regulatory region Sarah Milton Region: dlx5 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.3 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Facial papules v1.3 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Basal Cell Cancer v1.3 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Basal Cell Cancer v1.3 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Marked Region: ARHGAP36 downstream regulatory region as ready
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Red List (Low Evidence).
Hair disorders v0.90 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Hair disorders v0.90 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Added comment: Comment on list classification: Discussed with ZS
Mendeliome v1.4854 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Classified Region: ARHGAP36 downstream regulatory region as Green List (high evidence)
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Added comment: Comment on list classification: Discussed with ZS
Mendeliome v1.4853 ARHGAP36 downstream regulatory region Sarah Milton Region: arhgap36 downstream regulatory region has been classified as Green List (High Evidence).
Facial papules v1.2 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Facial papules v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Facial papules. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Basal Cell Cancer v1.2 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Basal Cell Cancer v1.2 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Basal Cell Cancer. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Intellectual disability syndromic and non-syndromic v1.780 SUPT4H1 Freeman A reviewed gene: SUPT4H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41842694; Phenotypes: intellectual disability, motor disability, speech impairment, dystonia, craniofacial dysmorphism, skeletal anomalies, enamel hypoplasia.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark Marked gene: CCDC134 as ready
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark Gene: ccdc134 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.447 Zornitza Stark Copied gene CCDC134 from panel Osteogenesis Imperfecta and Osteoporosis
Skeletal dysplasia v0.447 CCDC134 Zornitza Stark gene: CCDC134 was added
gene: CCDC134 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: CCDC134 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC134 were set to 32181939; 34204301; 35019224
Phenotypes for gene: CCDC134 were set to Osteogenesis imperfecta, type XXII, MIM#619795
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark Marked gene: C14orf80 as ready
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark Gene: c14orf80 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.446 Zornitza Stark Copied gene C14orf80 from panel Mendeliome
Skeletal dysplasia v0.446 C14orf80 Zornitza Stark gene: C14orf80 was added
gene: C14orf80 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
new gene name tags were added to gene: C14orf80.
Mode of inheritance for gene: C14orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C14orf80 were set to 39979680; 38252227; 30842647
Phenotypes for gene: C14orf80 were set to Primary microcephaly, MONDO:0016660
Skeletal dysplasia v0.445 APC Zornitza Stark Marked gene: APC as ready
Skeletal dysplasia v0.445 APC Zornitza Stark Gene: apc has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.445 APC Zornitza Stark gene: APC was added
gene: APC was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: APC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC were set to 30237576; 28383543; 25676610
Phenotypes for gene: APC were set to Syndromic disease, MONDO:0002254, APC-related
Review for gene: APC was set to RED
Added comment: PMID 25676610 reports 4 individuals from a Saudi consanguineous family with a homozygous APC splice‑site deletion and Cenani‑Lenz syndrome; PMID 28383543 reports another Saudi with homozygous APC splice‑site deletion and CLS; PMID 30237576 reports another Saudi individual with splice-site variant and CLS. All present with congenital limb malformations, syndactyly and scoliosis.

Likely founder variant. Possible multiple reports of same family.

All part of large cohorts with minimal additional information or functional validation, hence RED rating.
Sources: Literature
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.121 Chirag Patel Copied gene FOXA2 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.121 FOXA2 Chirag Patel gene: FOXA2 was added
gene: FOXA2 was added to Congenital hypothyroidism. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FOXA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXA2 were set to 28973288, 29329447, 30414530, 33729509, 31294511, 33999151
Phenotypes for gene: FOXA2 were set to Hypopituitarism, MONDO:0005152; Hyperinsulinism, MONDO:0002177
Pituitary hormone deficiency v0.227 TSHB Chirag Patel Marked gene: TSHB as ready
Pituitary hormone deficiency v0.227 TSHB Chirag Patel Gene: tshb has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.227 Chirag Patel Copied gene TSHB from panel Congenital hypothyroidism
Pituitary hormone deficiency v0.227 TSHB Chirag Patel gene: TSHB was added
gene: TSHB was added to Pituitary hormone deficiency. Sources: Expert Review Green,Genomics England PanelApp,Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSHB were set to 2792087; 27362444
Phenotypes for gene: TSHB were set to Congenital hypothyroidism; Hypothryoidism, congenital, nongoitrous 4, 275100; severe isolated central hypothyroidism
Callosome v0.595 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Callosome v0.595 FGF17 Zornitza Stark Gene: fgf17 has been classified as Red List (Low Evidence).
Callosome v0.595 FGF17 Zornitza Stark Phenotypes for gene: FGF17 were changed from to Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270
Callosome v0.594 FGF17 Zornitza Stark Classified gene: FGF17 as Red List (low evidence)
Callosome v0.594 FGF17 Zornitza Stark Gene: fgf17 has been classified as Red List (Low Evidence).
Callosome v0.593 FGF17 Zornitza Stark reviewed gene: FGF17: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: None
Autoimmune Lymphoproliferative Syndrome v1.12 KRAS Zornitza Stark Tag somatic tag was added to gene: KRAS.
Hand and foot malformations v0.90 ISCA-37467-Gain Sarah Milton Source Expert list was removed from Region: ISCA-37467-Gain.
Source Expert list was removed from Region: ISCA-37467-Gain.
Source Literature was added to Region: ISCA-37467-Gain.
Tag regulatory region was added to Region: ISCA-37467-Gain.
Hair disorders v0.89 Sarah Milton Copied Region ARHGAP36 downstream regulatory region from panel Mendeliome
Hair disorders v0.89 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Hair disorders. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Mendeliome v1.4852 ARHGAP36 downstream regulatory region Sarah Milton Region: ARHGAP36 downstream regulatory region was added
Region: ARHGAP36 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: ARHGAP36 downstream regulatory region.
Mode of inheritance for Region: ARHGAP36 downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: ARHGAP36 downstream regulatory region were set to PMID: 40015599; 35986704; 38713094
Phenotypes for Region: ARHGAP36 downstream regulatory region were set to Bazex-Dupre-Christol syndrome, MIM#301845
Review for Region: ARHGAP36 downstream regulatory region was set to GREEN
Added comment: ARHGAP36 is part of the Rho GTPase family and is a positive regulator of the SHH pathway.

At least 10 families have been reported in the literature with duplications in an agenic region downstream of ARHGAP36 presenting with Bazex-Dupre-Christol syndrome. This syndrome is characterised by a triad of follicular atrophoderma, hypotrichosis and basal cell neoplasms.

The duplications seen in affected individuals range from 18-135kb in size with the region thought to contain enhancers which increase expression of ARHGAP36.

Functional studies involving immunofluorescence of hair of affected individuals in telogen demonstrated increased expression of ARHGAP36.

Note: Coordinates used are the minimal region known to be duplicated in the reported cases.
Sources: Literature
Differences of Sex Development v1.55 ISCA-46303-Loss Sarah Milton Tag regulatory region was added to Region: ISCA-46303-Loss.
Skeletal dysplasia v0.444 DDX58 Zornitza Stark Marked gene: DDX58 as ready
Skeletal dysplasia v0.444 DDX58 Zornitza Stark Gene: ddx58 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.444 DDX58 Zornitza Stark changed review comment from: Comment when marking as ready: New HGNC approved name is RIGI.; to: New HGNC approved name is RIGI.

Syndrome with significant skeletal involvement.
Skeletal dysplasia v0.444 Zornitza Stark Copied gene DDX58 from panel Mendeliome
Skeletal dysplasia v0.444 DDX58 Zornitza Stark gene: DDX58 was added
gene: DDX58 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
new gene name tags were added to gene: DDX58.
Mode of inheritance for gene: DDX58 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX58 were set to 25620203; 30574673; 33495304
Phenotypes for gene: DDX58 were set to Singleton-Merten syndrome 2, MIM# 616298
Mode of pathogenicity for gene: DDX58 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v0.443 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Skeletal dysplasia v0.443 CWC27 Zornitza Stark Gene: cwc27 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.443 CWC27 Zornitza Stark changed review comment from: Highly variable phenotype characterised by RP and brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported.; to: Highly variable phenotype characterised by RP and metaphyseal chondrodysplasia, typically brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported.
Skeletal dysplasia v0.443 Zornitza Stark Copied gene CWC27 from panel Mendeliome
Skeletal dysplasia v0.443 CWC27 Zornitza Stark gene: CWC27 was added
gene: CWC27 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CWC27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWC27 were set to 28285769; 31481716
Phenotypes for gene: CWC27 were set to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Skeletal dysplasia v0.442 CSF1R Zornitza Stark Marked gene: CSF1R as ready
Skeletal dysplasia v0.442 CSF1R Zornitza Stark Gene: csf1r has been classified as Green List (High Evidence).
Skeletal dysplasia v0.442 Zornitza Stark Copied gene CSF1R from panel Brain Calcification
Skeletal dysplasia v0.442 CSF1R Zornitza Stark gene: CSF1R was added
gene: CSF1R was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: CSF1R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSF1R were set to 30982609; 33749994; 34135456
Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, MIM# 618476; BANDDOS
Skeletal dysplasia v0.441 CEP295 Zornitza Stark Classified gene: CEP295 as Green List (high evidence)
Skeletal dysplasia v0.441 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Classified gene: CEP295 as Green List (high evidence)
Skeletal dysplasia v0.440 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.439 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Marked gene: CENPJ as ready
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Gene: cenpj has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Classified gene: CENPJ as Amber List (moderate evidence)
Skeletal dysplasia v0.438 CENPJ Zornitza Stark Gene: cenpj has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.437 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPJ were set to 34068194
Phenotypes for gene: CENPJ were set to Seckel syndrome 4, MIM# 613676
Review for gene: CENPJ was set to AMBER
Added comment: PMID 34068194 reports 3 individuals from 2 unrelated families with autosomal recessive homozygous CENPJ variants presenting with Seckel syndrome. Functional assays (RT‑PCR splice assay, immunoblot, immunofluorescence) demonstrate aberrant splicing, reduced CENPJ protein and centrosome amplification, supporting pathogenicity.
Sources: Literature
Motor Neurone Disease v1.49 RBMX Zornitza Stark Marked gene: RBMX as ready
Motor Neurone Disease v1.49 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.58 RBMX Zornitza Stark Marked gene: RBMX as ready
Early-onset Dementia v1.58 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Growth failure v1.107 SLC6A17 Zornitza Stark Marked gene: SLC6A17 as ready
Growth failure v1.107 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Green List (High Evidence).
Mendeliome v1.4851 SUPT6H Zornitza Stark Marked gene: SUPT6H as ready
Mendeliome v1.4851 SUPT6H Zornitza Stark Gene: supt6h has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.780 SUPT6H Zornitza Stark Marked gene: SUPT6H as ready
Intellectual disability syndromic and non-syndromic v1.780 SUPT6H Zornitza Stark Gene: supt6h has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark Marked gene: ADGB as ready
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.156 Zornitza Stark Copied gene ADGB from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.156 ADGB Zornitza Stark gene: ADGB was added
gene: ADGB was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGB were set to 38385883; 36995441
Phenotypes for gene: ADGB were set to Infertility disorder, MONDO:0005047, ADGB-related
Mendeliome v1.4851 ADGB Zornitza Stark Marked gene: ADGB as ready
Mendeliome v1.4851 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Mendeliome v1.4851 ADGB Zornitza Stark Classified gene: ADGB as Green List (high evidence)
Mendeliome v1.4851 ADGB Zornitza Stark Gene: adgb has been classified as Green List (High Evidence).
Speech apraxia v1.40 KDM5C Zornitza Stark Classified gene: KDM5C as Green List (high evidence)
Speech apraxia v1.40 KDM5C Zornitza Stark Gene: kdm5c has been classified as Green List (High Evidence).
Speech apraxia v1.39 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Speech apraxia v1.39 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Speech apraxia v1.39 SCN8A Zornitza Stark Classified gene: SCN8A as Green List (high evidence)
Speech apraxia v1.39 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Speech apraxia v1.38 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Speech apraxia v1.38 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Speech apraxia v1.38 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Green List (high evidence)
Speech apraxia v1.38 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Speech apraxia v1.37 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Speech apraxia v1.37 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Speech apraxia v1.37 FOXP1 Zornitza Stark Classified gene: FOXP1 as Green List (high evidence)
Speech apraxia v1.37 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Green List (High Evidence).
Speech apraxia v1.36 SET Zornitza Stark Marked gene: SET as ready
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.36 SET Zornitza Stark Classified gene: SET as Green List (high evidence)
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.35 GNAI1 Zornitza Stark Marked gene: GNAI1 as ready
Speech apraxia v1.35 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Speech apraxia v1.35 GNAI1 Zornitza Stark Classified gene: GNAI1 as Green List (high evidence)
Speech apraxia v1.35 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.33 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Speech apraxia v1.33 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Speech apraxia v1.33 SLC6A1 Zornitza Stark Classified gene: SLC6A1 as Green List (high evidence)
Speech apraxia v1.33 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Speech apraxia v1.32 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Speech apraxia v1.32 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Speech apraxia v1.32 SMARCA2 Zornitza Stark Classified gene: SMARCA2 as Green List (high evidence)
Speech apraxia v1.32 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark Marked gene: CHCHD4 as ready
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mitochondrial disease v1.23 Zornitza Stark Copied gene CHCHD4 from panel Mendeliome
Mitochondrial disease v1.23 CHCHD4 Zornitza Stark gene: CHCHD4 was added
gene: CHCHD4 was added to Mitochondrial disease. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CHCHD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHCHD4 were set to 41981912; 26004228
Phenotypes for gene: CHCHD4 were set to Mitochondrial disease, MONDO:0044970, CHCHD4-related
Mendeliome v1.4850 CHCHD4 Zornitza Stark Marked gene: CHCHD4 as ready
Mendeliome v1.4850 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4850 CHCHD4 Zornitza Stark Phenotypes for gene: CHCHD4 were changed from IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression to Mitochondrial disease, MONDO:0044970, CHCHD4-related
Mendeliome v1.4849 CHCHD4 Zornitza Stark Classified gene: CHCHD4 as Red List (low evidence)
Mendeliome v1.4849 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4848 CHCHD4 Zornitza Stark reviewed gene: CHCHD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, CHCHD4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.107 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Growth failure v1.107 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Growth failure v1.106 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Intellectual disability syndromic and non-syndromic v1.780 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Intellectual disability syndromic and non-syndromic v1.779 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.779 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Microcephaly v1.434 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Microcephaly v1.433 CDK4 Lucy Spencer Classified gene: CDK4 as Green List (high evidence)
Microcephaly v1.433 CDK4 Lucy Spencer Gene: cdk4 has been classified as Green List (High Evidence).
Microcephaly v1.432 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.778 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Growth failure v1.105 Lucy Spencer Added reviews for gene CDK4 from panel Mendeliome
Mendeliome v1.4848 CDK4 Lucy Spencer Publications for gene: CDK4 were set to 40210435
Mendeliome v1.4847 CDK4 Lucy Spencer reviewed gene: CDK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41856556; Phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4847 ADGB Rylee Peters gene: ADGB was added
gene: ADGB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGB were set to 38385883; 36995441
Phenotypes for gene: ADGB were set to Infertility disorder, MONDO:0005047, ADGB-related
Review for gene: ADGB was set to GREEN
Added comment: PMID: 36995441 and PMID: 38385883 report four unrelated individuals with biallelic ADGB variants causing severe asthenoteratozoospermia. Functional studies including loss of ADGB protein in patient sperm and Adgb-/- male mice were infertile with immobile sperm.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.777 Lucy Spencer Copied gene SUPT6H from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.777 SUPT6H Lucy Spencer gene: SUPT6H was added
gene: SUPT6H was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SUPT6H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT6H were set to 41864309
Phenotypes for gene: SUPT6H were set to Neurodevelopmental disorder, MONDO:0700092, SUPT6H-related
Mendeliome v1.4846 SUPT6H Lucy Spencer Classified gene: SUPT6H as Amber List (moderate evidence)
Mendeliome v1.4846 SUPT6H Lucy Spencer Gene: supt6h has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4845 SUPT6H Lucy Spencer gene: SUPT6H was added
gene: SUPT6H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT6H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT6H were set to 41864309
Phenotypes for gene: SUPT6H were set to Neurodevelopmental disorder, MONDO:0700092, SUPT6H-related
Review for gene: SUPT6H was set to AMBER
Added comment: PMID 41864309 reports 18 individuals from 18 unrelated families with heterozygous SUPT6H variants presenting with a neurodevelopmental disorder. All individuals were from large cohorts of individuals with developmental disorders (including the DECIPHER cohort) and phenotype information was limited but features included: autism‑spectrum, developmental delay, and occasional congenital heart disease or orofacial clefting.

All but 5 of the reported variants were present in gnomad with 3 or more hets. Asp175His, Lys256Arg, Arg380Gly, Gln517Lys and Trp1065* were all absent but 3 of these individuals were only listed as having CHD or autism. It is unclear whether the variants in this cohort were de novo however 4 of the 18 variants are in DECIPHER and all listed as de novo including Arg380Gly and Trp1065* which were absent from gnomad. Arg1495Gln and Arg1660Trp were also de novo in DECIPHER but have 6 and 34 hets respectively in gnomad.

Heterozygous KO mice were not viable and parvalbumin‑specific conditional Supt6 knockout mice recapitulate motor impairment, seizures and depression‑like behavior. No functional performed on the variants.

Only 5 of the 18 variants were absent from gnomad, limited phenotype information available and the things that are listed are not very consistent or specific, inheritance information not available for the vast majority. Amber but close to green
Sources: Literature
Mendeliome v1.4844 CHCHD4 Isabelle Adant gene: CHCHD4 was added
gene: CHCHD4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHCHD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHCHD4 were set to 41981912; 26004228
Phenotypes for gene: CHCHD4 were set to IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression
Review for gene: CHCHD4 was set to RED
Added comment: 41981912
1 individual compound heterozygous for missense variant and large deletion
encompassing the whole CHCHD4 gene (and adjacent gene) of biparental inheritance,
presenting with IUGR, liver dysfunction, lactic acidosis and short-fasting
hypoglycaemia, developmental delay and regression, hypertonia and
dystonia. Early demise at 11months.
Minimal supporting biochemical evidence (protein expression studies) in patient-derived fibroblasts.

26004228 : Chchd4−/− mouse model
Biallelic Chchd4 in mouse embryos causes a developmental arrest coupled
with embryonic lethality at the onset of gastrulation. The developmental
retardation of Chchd4−/− embryos was accompanied by a major defect in the
expression of respiratory chain complex I subunit CI-20.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Autism v0.250 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Autism v0.250 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.776 Zornitza Stark Copied gene WWP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.776 WWP1 Zornitza Stark gene: WWP1 was added
gene: WWP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: WWP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WWP1 were set to 41786693; 32699206
Phenotypes for gene: WWP1 were set to Neurodevelopmental disorder, MONDO:0700092, WWP1-related
Autism v0.250 Zornitza Stark Copied gene WWP1 from panel Mendeliome
Autism v0.250 WWP1 Zornitza Stark gene: WWP1 was added
gene: WWP1 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: WWP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WWP1 were set to 41786693; 32699206
Phenotypes for gene: WWP1 were set to Neurodevelopmental disorder, MONDO:0700092, WWP1-related
Mendeliome v1.4844 WWP1 Zornitza Stark Marked gene: WWP1 as ready
Mendeliome v1.4844 WWP1 Zornitza Stark Gene: wwp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.414 PIGM Zornitza Stark Marked gene: PIGM as ready
Genetic Epilepsy v1.414 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Genetic Epilepsy v1.414 Zornitza Stark Copied gene PIGM from panel Mendeliome
Genetic Epilepsy v1.414 PIGM Zornitza Stark gene: PIGM was added
gene: PIGM was added to Genetic Epilepsy. Sources: Expert Review Green,Victorian Clinical Genetics Services
founder tags were added to gene: PIGM.
Mode of inheritance for gene: PIGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGM were set to 31445883; 16767100; 41782195; 39912323; 39425582; 39119839
Phenotypes for gene: PIGM were set to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v1.88 PIGM Zornitza Stark Publications for gene: PIGM were set to 31445883; 16767100
Congenital Disorders of Glycosylation v1.87 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Congenital Disorders of Glycosylation v1.87 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.86 PIGM Zornitza Stark edited their review of gene: PIGM: Added comment: Sufficient evidence now for Green rating.; Changed rating: GREEN
Mendeliome v1.4844 PIGM Zornitza Stark Publications for gene: PIGM were set to 31445883; 16767100
Mendeliome v1.4843 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Mendeliome v1.4843 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Mendeliome v1.4843 PIGM Zornitza Stark Classified gene: PIGM as Green List (high evidence)
Mendeliome v1.4843 PIGM Zornitza Stark Gene: pigm has been classified as Green List (High Evidence).
Mendeliome v1.4842 PIGM Zornitza Stark reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 41782195, 39912323, 39425582, 39119839, 31445883; Phenotypes: Glycosylphosphatidylinositol deficiency, MIM# 610293; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.576 Zornitza Stark removed gene:NME8 from the panel
Heterotaxy v1.45 NME8 Zornitza Stark Tag disputed tag was added to gene: NME8.
Ciliary Dyskinesia v1.77 NME8 Zornitza Stark Tag disputed tag was added to gene: NME8.
Cardiomyopathy_Paediatric v0.231 ASNA1 Zornitza Stark Tag new gene name tag was added to gene: ASNA1.
Fetal anomalies v1.575 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Fetal anomalies v1.574 EMG1 Zornitza Stark edited their review of gene: EMG1: Added comment: Affected individuals present with severe developmental delay, microcephaly, growth failure, micrognathia, joint contractures and early death. Functional studies show loss‑of‑function through protein destabilisation, reduced EMG1 levels, binucleate fibroblasts, G2/M arrest, impaired 18S rRNA processing and recapitulation of the phenotype in a mouse knock‑in model.

GDA to remain as AMBER as the same founder variant in the Hutterite population has been reported in the additional PMIDs and could potentially be the same families. Further reports would be required to upgrade to Green.; Changed publications: 19463982, 27798105, 26676230, 25708872
Intellectual disability syndromic and non-syndromic v1.775 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Intellectual disability syndromic and non-syndromic v1.774 EMG1 Zornitza Stark Tag founder tag was added to gene: EMG1.
Intellectual disability syndromic and non-syndromic v1.774 EMG1 Zornitza Stark edited their review of gene: EMG1: Added comment: Affected individuals present with severe developmental delay, microcephaly, growth failure, micrognathia, joint contractures and early death. Functional studies show loss‑of‑function through protein destabilisation, reduced EMG1 levels, binucleate fibroblasts, G2/M arrest, impaired 18S rRNA processing and recapitulation of the phenotype in a mouse knock‑in model.

GDA to remain as AMBER as the same founder variant in the Hutterite population has been reported in the additional PMIDs and could potentially be the same families. Further reports would be required to upgrade to Green.; Changed publications: 19463982, 27798105, 26676230, 25708872
Mendeliome v1.4842 EMG1 Zornitza Stark Tag founder tag was added to gene: EMG1.
Mendeliome v1.4842 EMG1 Zornitza Stark Publications for gene: EMG1 were set to 19463982
Mendeliome v1.4841 RASA2 Zornitza Stark Publications for gene: RASA2 were set to
Fetal anomalies v1.574 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Fetal anomalies v1.574 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Fetal anomalies v1.574 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Fetal anomalies v1.573 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Fetal anomalies v1.573 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.259 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Syndromic Retinopathy v0.258 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Syndromic Retinopathy v0.258 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mitochondrial disease v1.22 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Mitochondrial disease v1.21 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Mitochondrial disease v1.21 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mitochondrial disease v1.20 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Changed rating: GREEN
Mitochondrial disease v1.20 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Added comment: TOMM7 encodes translocase of outer mitochondrial membrane 7 which is involved in transporting relevant proteins from the cytosol to the mitochondrial membrane.

PMIDs 36282599, 39615461 report 10 individuals from 8 unrelated families with a recurrent biallelic TOMM7 missense variant - p.(Pro29Leu).
The clinical presentation encompassed a progeroid syndrome with severe short stature (-4 to -7SD), mandibular hypoplasia, facial dysmorphism, atrophic macular scarring, microcephaly and moyamoya disease (5/10)

Functional studies in patient cells showed differing results based on cell type. Supportive knockout mouse and zebrafish studies. Mechanism of recurrent missense variant not fully elucidated.; Changed publications: 36299998, 36282599, 39615461
Microcephaly v1.431 TOMM7 Zornitza Stark Marked gene: TOMM7 as ready
Microcephaly v1.431 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Microcephaly v1.431 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Microcephaly v1.430 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Microcephaly v1.430 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Mendeliome v1.4840 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to 36299998; 36282599
Mendeliome v1.4839 TOMM7 Zornitza Stark Classified gene: TOMM7 as Green List (high evidence)
Mendeliome v1.4839 TOMM7 Zornitza Stark Gene: tomm7 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.155 TDRD6 Zornitza Stark Publications for gene: TDRD6 were set to 39764564; 39331689
Infertility and Recurrent Pregnancy Loss v1.154 TDRD6 Zornitza Stark Classified gene: TDRD6 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.154 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Green List (High Evidence).
Mendeliome v1.4838 TDRD6 Zornitza Stark Classified gene: TDRD6 as Green List (high evidence)
Mendeliome v1.4838 TDRD6 Zornitza Stark Gene: tdrd6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.153 TDRD12 Zornitza Stark Publications for gene: TDRD12 were set to 40750267
Infertility and Recurrent Pregnancy Loss v1.152 TDRD12 Zornitza Stark Classified gene: TDRD12 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.152 TDRD12 Zornitza Stark Gene: tdrd12 has been classified as Green List (High Evidence).
Mendeliome v1.4837 TDRD12 Zornitza Stark Publications for gene: TDRD12 were set to 40750267
Mendeliome v1.4836 TDRD12 Zornitza Stark Classified gene: TDRD12 as Green List (high evidence)
Mendeliome v1.4836 TDRD12 Zornitza Stark Gene: tdrd12 has been classified as Green List (High Evidence).
Mitochondrial disease v1.20 OXA1L Zornitza Stark Publications for gene: OXA1L were set to 30201738
Mitochondrial disease v1.19 OXA1L Zornitza Stark Classified gene: OXA1L as Green List (high evidence)
Mitochondrial disease v1.19 OXA1L Zornitza Stark Gene: oxa1l has been classified as Green List (High Evidence).
Mitochondrial disease v1.18 OXA1L Zornitza Stark reviewed gene: OXA1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 40551575, 30201738; Phenotypes: Combined oxidative phosphorylation deficiency (MONDO:0000732), OXA1L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v1.18 OXA1L Zornitza Stark Deleted their review
Mendeliome v1.4835 OXA1L Zornitza Stark Publications for gene: OXA1L were set to 30201738; 16435202
Mendeliome v1.4834 OXA1L Zornitza Stark Classified gene: OXA1L as Green List (high evidence)
Mendeliome v1.4834 OXA1L Zornitza Stark Gene: oxa1l has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark Marked gene: LRRC23 as ready
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.151 Zornitza Stark Copied gene LRRC23 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.151 LRRC23 Zornitza Stark gene: LRRC23 was added
gene: LRRC23 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: LRRC23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC23 were set to 37804054; 38091523; 39054792
Phenotypes for gene: LRRC23 were set to Spermatogenic failure 92, MIM# 620848
Mendeliome v1.4833 LRRC23 Zornitza Stark Publications for gene: LRRC23 were set to 37804054; 38091523
Mendeliome v1.4832 LRRC23 Zornitza Stark Classified gene: LRRC23 as Green List (high evidence)
Mendeliome v1.4832 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.774 KLHL15 Zornitza Stark Publications for gene: KLHL15 were set to 25644381; 24817631
Intellectual disability syndromic and non-syndromic v1.773 KLHL15 Zornitza Stark Classified gene: KLHL15 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.773 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.772 KLHL15 Zornitza Stark edited their review of gene: KLHL15: Added comment: Additional male individual presenting with impaired intelligence, short stature, frequent hypoglycaemia and periodic fever.
Hemizygous variant was identified in the proband c.736 C>T p.(Arg246*) - absent from gnomAD v4.1; Changed rating: GREEN; Changed publications: 25644381, 24817631, 37452054; Changed phenotypes: intellectual disability, X-linked 103 MONDO:0010508
Mendeliome v1.4831 KLHL15 Zornitza Stark Phenotypes for gene: KLHL15 were changed from Mental retardation, X-linked 103, MIM#300982 to intellectual disability, X-linked 103 MONDO:0010508
Mendeliome v1.4830 KLHL15 Zornitza Stark Publications for gene: KLHL15 were set to 25644381; 24817631
Mendeliome v1.4829 KLHL15 Zornitza Stark Classified gene: KLHL15 as Green List (high evidence)
Mendeliome v1.4829 KLHL15 Zornitza Stark Gene: klhl15 has been classified as Green List (High Evidence).
Fetal anomalies v1.572 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Fetal anomalies v1.571 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Fetal anomalies v1.571 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Fetal anomalies v1.570 HAND1 Zornitza Stark reviewed gene: HAND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39537763, 39107573, 38551686; Phenotypes: congenital heart disease, MONDO:0005453; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.540 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Congenital Heart Defect v0.539 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Congenital Heart Defect v0.539 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Mendeliome v1.4828 HAND1 Zornitza Stark Publications for gene: HAND1 were set to 31286141; 29016838; 29317578; 29179274; 28112363; 27942761; 26581070
Mendeliome v1.4827 HAND1 Zornitza Stark Classified gene: HAND1 as Green List (high evidence)
Mendeliome v1.4827 HAND1 Zornitza Stark Gene: hand1 has been classified as Green List (High Evidence).
Hair disorders v0.88 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 31332722
Hair disorders v0.87 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Hair disorders v0.87 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.772 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to PMID: 28973399
Intellectual disability syndromic and non-syndromic v1.771 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.771 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.27 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 26996949
Chromosome Breakage Disorders v1.26 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Chromosome Breakage Disorders v1.26 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.25 GTF2E2 Zornitza Stark edited their review of gene: GTF2E2: Added comment: 3 additional unrelated families presenting with brittle, tiger‑tail banded hair, ichthyosis, short stature, microcephaly, developmental delay, anemia, autism spectrum disorder and abnormal hemoglobin fractions reported with biallelic variants.; Changed rating: GREEN; Changed publications: 26996949, 37793898, 31064989, 28973399
Mendeliome v1.4826 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to 26996949
Mendeliome v1.4825 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Green List (high evidence)
Mendeliome v1.4825 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 SMARCA2 Hali Van Niel gene: SMARCA2 was added
gene: SMARCA2 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA2 were set to 41530369; 39931922; 32694869
Phenotypes for gene: SMARCA2 were set to Nicolaides-Baraitser syndrome (MIM#601358); Blepharophimosis-impaired intellectual development syndrome (MIM#619293)
Review for gene: SMARCA2 was set to GREEN
Added comment: Two reported individual with CAS and de novo missense variants (c.2870 A > G; p.(Gln957Arg); c.3484 C > T; p.(Arg1162Cys)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic findings from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SMARCA2 variant (Supp Table 6).

Phenotype dependent on variant position along gene (PMID: 32694869). Both phenotypes implicated with CAS.
Sources: Expert List, Literature
Speech apraxia v1.31 SLC6A1 Hali Van Niel gene: SLC6A1 was added
gene: SLC6A1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A1 were set to 41530369; 39931922
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy (MIM#616421
Review for gene: SLC6A1 was set to GREEN
Added comment: Reported individual with CAS and de novo missense variant (c.1097_1098delinsCT; p.(Leu366Pro)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

Mitchel et al. (2025; PMID: 39931922) report two individuals with dysarthria and SLC6A1 variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 SETD5 Hali Van Niel gene: SETD5 was added
gene: SETD5 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 41530369; 39931922
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, 23 (MIM#615761)
Review for gene: SETD5 was set to GREEN
Added comment: Reported individual with CAS and de novo splicing variant (c.2347-7 A > G) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report five individuals SETD5 variants (4 with CAS, 1 with dysarthria).

Unspecified speech delay/impairment reported commonly in individuals with SETD5 variants (PMID: 29484850)
Sources: Expert List, Literature
Speech apraxia v1.31 GNAI1 Hali Van Niel changed review comment from: Reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369), Validated C4 finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype has variable expressivity ranging from mild to severe (PMID: 33473207); to: Reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369), Validated C4 finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype is variable ranging from mild to severe (PMID: 33473207)
Speech apraxia v1.31 SET Hali Van Niel gene: SET was added
gene: SET was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SET were set to 41530369; 39931922
Phenotypes for gene: SET were set to Intellectual developmental disorder, 58 (MIM#618106).
Review for gene: SET was set to GREEN
Added comment: Reported individual with CAS and de novo nonsense variant (c.103_104del; p.(Ile35*)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SET variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature; to: Individual with CAS reported with nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369).

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 PPP2R5D Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature; to: Individual with CAS reported with de novo missense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature
Mendeliome v1.4824 RASA2 Rylee Peters reviewed gene: RASA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 41854160, 25049390; Phenotypes: Noonan syndrome MONDO:0018997, RASA2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia and Chorea v0.346 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Dystonia and Chorea v0.345 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Dystonia and Chorea v0.345 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.344 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia
Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1
The sibling was not tested but both healthy parents were identified as heterozygous.; Changed rating: GREEN; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Intellectual disability syndromic and non-syndromic v1.770 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Intellectual disability syndromic and non-syndromic v1.769 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.769 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.768 GSX2 Zornitza Stark edited their review of gene: GSX2: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.768 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia
Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1
The sibling was not tested but both healthy parents were identified as heterozygous.; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Cerebral Palsy v1.412 GSX2 Zornitza Stark Publications for gene: GSX2 were set to 31412107
Cerebral Palsy v1.411 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Cerebral Palsy v1.411 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.410 GSX2 Zornitza Stark edited their review of gene: GSX2: Changed rating: GREEN
Cerebral Palsy v1.410 GSX2 Zornitza Stark edited their review of gene: GSX2: Added comment: PMID 39119454: Additional report of siblings from a consanguineous family affected with diencephalic-mesencephalic junction dysplasia Proband was tested, and a homozygous variant was identified: c.747G>C (p.Trp249Cys) - variant is absent in gnomAD v4.1 The sibling was not tested but both healthy parents were identified as heterozygous.; Changed publications: 31412107, 39119454; Changed phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 2 618646, Intellectual disability, Dystonia, Spastic tetra paresis
Mendeliome v1.4824 GSX2 Zornitza Stark Publications for gene: GSX2 were set to PMID: 31412107
Mendeliome v1.4823 GSX2 Zornitza Stark Classified gene: GSX2 as Green List (high evidence)
Mendeliome v1.4823 GSX2 Zornitza Stark Gene: gsx2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 PPP2R5D Hali Van Niel gene: PPP2R5D was added
gene: PPP2R5D was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5D were set to 41530369; 39931922; 32074998
Phenotypes for gene: PPP2R5D were set to Intellectual developmental disorder 35 (MIM#616355)
Review for gene: PPP2R5D was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature
Bone Marrow Failure v1.145 RPL18 Zornitza Stark Publications for gene: RPL18 were set to PMID: 28280134, 32075953
Bone Marrow Failure v1.144 RPL18 Zornitza Stark reviewed gene: RPL18: Rating: AMBER; Mode of pathogenicity: None; Publications: 41851260, 40510848; Phenotypes: Diamond-Blackfan anemia 18, MONDO:0032668; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.57 RPL18 Zornitza Stark Phenotypes for gene: RPL18 were changed from Diamond-Blackfan anemia 18, MIM# 618310 to Diamond-Blackfan anaemia 18, MIM# 618310
Red cell disorders v1.56 RPL18 Zornitza Stark Publications for gene: RPL18 were set to 28280134; 32075953
Red cell disorders v1.55 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

All variants are absent from gnomAD.; Changed publications: 28280134, 32075953, 40510848, 41851260; Changed phenotypes: Diamond-Blackfan anemia 18, MIM# 618310
Mendeliome v1.4822 RPL18 Zornitza Stark changed review comment from: Three recent studies add 3 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

PMID 28280134 reports one autosomal‑dominant family (father‑son) with heterozygous p.L51S; patient mononuclear cells display 36S pre‑rRNA accumulation, indicating a ribosome‑biogenesis defect.

All variants are absent from gnomAD.; to: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

All variants are absent from gnomAD.
Diamond Blackfan anaemia v1.22 RPL18 Zornitza Stark Phenotypes for gene: RPL18 were changed from Diamond-Blackfan anemia 18, MIM# 618310 to Diamond-Blackfan anaemia 18, MIM# 618310
Diamond Blackfan anaemia v1.21 RPL18 Zornitza Stark Publications for gene: RPL18 were set to 28280134; 32075953
Diamond Blackfan anaemia v1.20 RPL18 Zornitza Stark changed review comment from: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.; to: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.
Diamond Blackfan anaemia v1.20 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Two recent studies add 2 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

Variants are absent from gnomAD.; Changed publications: 28280134, 32075953, 41851260, 40510848; Changed phenotypes: Diamond-Blackfan anaemia 18, MIM# 618310
Speech apraxia v1.31 SCN8A Hali Van Niel gene: SCN8A was added
gene: SCN8A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN8A were set to 41530369; 39931922
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia (MIM#614306)
Review for gene: SCN8A was set to GREEN
Added comment: One reported individual with CAS and de novo missense variant, c.417 G > A; p.(Met139Ile) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report two individuals with CAS and SCN8A variants (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel changed review comment from: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369)

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature; to: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 41530369, 39931922; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 KDM5C Hali Van Niel Deleted their review
Speech apraxia v1.31 EHMT1 Hali Van Niel changed review comment from: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369)

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List; to: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List
Speech apraxia v1.31 EBF3 Hali Van Niel changed review comment from: Additional individuals:

One with dysarthria reported with de novo deletion in EBF3 (c.708_710delCAA; p.(Asn237del)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 4 individuals with EBF3 variants (1 with CAS, 3 with dysarthria); to: Additional individuals:

One with dysarthria reported with de novo deletion in EBF3 (c.708_710delCAA; p.(Asn237del)) (Van Niel et al., 2026; PMID: 41530369) Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 4 individuals with EBF3 variants (1 with CAS, 3 with dysarthria)
Speech apraxia v1.31 CAMTA1 Hali Van Niel changed review comment from: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature; to: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369) Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature
Speech apraxia v1.31 CACNA1A Hali Van Niel changed review comment from: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature; to: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic findings from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 GNAI1 Hali Van Niel reviewed gene: GNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 41530369, 9931922, 33473207); Phenotypes: Neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities (MIM#619854); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.4822 RPL18 Zornitza Stark edited their review of gene: RPL18: Changed rating: AMBER
Mendeliome v1.4822 RPL18 Zornitza Stark edited their review of gene: RPL18: Added comment: Three recent studies add 3 unrelated families with Diamond‑Blackfan anaemia and RPL18 variants.

PMID 40510848 reports one autosomal‑recessive family with compound‑heterozygous missense variants (p.Phe43Ser, p.Asp348Asn). LIMITED evidence for this MOI.

Leschchynska2026 describes one autosomal‑dominant family (3 affected family members) with heterozygous p.G133R and VACTERL anomalies and anaemia; functional assays show protein instability and 22 % reduced protein synthesis. However, another RPS6 variant co-segregates with disease also.

PMID 28280134 reports one autosomal‑dominant family (father‑son) with heterozygous p.L51S; patient mononuclear cells display 36S pre‑rRNA accumulation, indicating a ribosome‑biogenesis defect.

All variants are absent from gnomAD.; Changed rating: GREEN; Changed publications: 41851260, 40510848, 28280134; Changed phenotypes: Diamond-Blackfan anemia 18, MONDO:0032668
Speech apraxia v1.31 GNAI1 Hali Van Niel Deleted their review
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Microcephaly v1.429 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Microcephaly v1.429 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Microcephaly v1.429 Zornitza Stark Copied gene OLA1 from panel Mendeliome
Microcephaly v1.429 OLA1 Zornitza Stark gene: OLA1 was added
gene: OLA1 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Intellectual disability syndromic and non-syndromic v1.768 Zornitza Stark Copied gene OLA1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.768 OLA1 Zornitza Stark gene: OLA1 was added
gene: OLA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Mendeliome v1.4822 OLA1 Zornitza Stark Marked gene: OLA1 as ready
Mendeliome v1.4822 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Mendeliome v1.4822 OLA1 Zornitza Stark Phenotypes for gene: OLA1 were changed from Neurodevelopmental disorder with hypermobility to Neurodevelopmental disorder, MONDO:0700092, OLA1-related
Mendeliome v1.4821 OLA1 Zornitza Stark Classified gene: OLA1 as Green List (high evidence)
Mendeliome v1.4821 OLA1 Zornitza Stark Gene: ola1 has been classified as Green List (High Evidence).
Mendeliome v1.4820 OLA1 Zornitza Stark reviewed gene: OLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, OLA1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hair disorders v0.86 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 27049303; 27550540
Hair disorders v0.85 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Hair disorders v0.85 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Hair disorders v0.84 KREMEN1 Zornitza Stark reviewed gene: KREMEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28813618; Phenotypes: ectodermal dysplasia 13, hair/tooth type, MONDO:0044305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.112 KREMEN1 Zornitza Stark changed review comment from: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (parse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene); to: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (sparse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene)
Ectodermal Dysplasia v0.112 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 29526031; 29526031
Ectodermal Dysplasia v0.111 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Ectodermal Dysplasia v0.111 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.110 KREMEN1 Zornitza Stark edited their review of gene: KREMEN1: Changed rating: GREEN
Ectodermal Dysplasia v0.110 KREMEN1 Zornitza Stark edited their review of gene: KREMEN1: Added comment: Two additional unrelated families with suspected tooth agenesis reported in PMID 28813618.
Probands presented with mild clinical features of ectodermal dysplasia (parse hair, dry skin, sparse eyebrows and eyelashes, protruded lips, and heat intolerance)
Homozygous variants were identified in each proband (c.146C>G, p.T49R and c.773_778del - both rare in gnomAD v4.1 for AR gene); Changed publications: 29526031, 29526031, 28813618
Mendeliome v1.4820 KREMEN1 Zornitza Stark Publications for gene: KREMEN1 were set to 27049303; 27550540
Mendeliome v1.4819 KREMEN1 Zornitza Stark Classified gene: KREMEN1 as Green List (high evidence)
Mendeliome v1.4819 KREMEN1 Zornitza Stark Gene: kremen1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.436 Zornitza Stark removed gene:SUPT4H1 from the panel
Intellectual disability syndromic and non-syndromic v1.767 NPRL2 Lucy Spencer Classified gene: NPRL2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.767 NPRL2 Lucy Spencer Gene: nprl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.766 NPRL2 Lucy Spencer edited their review of gene: NPRL2: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.766 NPRL2 Lucy Spencer changed review comment from: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Borderline amber/green for this panel
Sources: Literature; to: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Sources: Literature
Mendeliome v1.4818 OLA1 Fahaz Nazer gene: OLA1 was added
gene: OLA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Neurodevelopmental disorder with hypermobility
Review for gene: OLA1 was set to GREEN
Added comment: Autosomal recessive NDD with hypermobility

14 affected individuals from 9 unrelated families
6 individuals had significant microcephaly. All have ID.

Variant in Family 1: Arg143* - proven to cause complete loss of OLA1 protein on Western Blot.

Ola1 null mice are small for gestational age, exhibit developmental delay, and have high perinatal lethality

Functional evidence (C.Elegans model):
Assessed 2 independent LOF alleles.
Notable behavioral effects (reduced bending, and response to touch)
GABAergic motor neurons shows abnormal axonal architecture and projection defects
Sources: Literature
Skeletal dysplasia v0.435 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Skeletal dysplasia v0.435 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Intellectual disability syndromic and non-syndromic v1.766 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.766 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Amelogenesis imperfecta v1.15 Sarah Milton Copied gene SUPT4H1 from panel Mendeliome
Amelogenesis imperfecta v1.15 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Mendeliome v1.4818 SUPT4H1 Sarah Milton gene: SUPT4H1 was added
gene: SUPT4H1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT4H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT4H1 were set to 41842694
Phenotypes for gene: SUPT4H1 were set to Syndromic disease, MONDO:0002254, SUPT4H1-related
Review for gene: SUPT4H1 was set to GREEN
Added comment: SUPT4H1 encodes SPT4 which is a subunit of the DSIF complex that regulates RNA polymerase II transcription.

PMID 41842694 reports six individuals from three unrelated families with biallelic loss‑of‑function SUPT4H1 variants. 2 families were consanguineous, the other was not noted to have been.

Clinical presentations of affected individuals included moderate to severe intellectual disability, dystonia, speech impairment, dysmorphism, skeletal anomalies including vertebral fusion/bifid vertebrae and complete enamel hypoplasia in 6/6 individuals.
Variable additional features included epilepsy, spasticity and congenital heart defects.

Variants were homozygous with one extension and 2 missense variants. Loss of function presumed mechanism.

Supportive functional studies included altered transcriptomics and proteomics of other genes/proteins across patient samples. C. elegans knockout and variant knock‑in models demonstrated altered movement and behaviour.
Sources: Literature
Bleeding and Platelet Disorders v1.78 KLKB1 Zornitza Stark Classified gene: KLKB1 as Green List (high evidence)
Bleeding and Platelet Disorders v1.78 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Green List (High Evidence).
Mendeliome v1.4817 KLKB1 Zornitza Stark Publications for gene: KLKB1 were set to 15461630; 33073460
Mendeliome v1.4816 KLKB1 Zornitza Stark Classified gene: KLKB1 as Green List (high evidence)
Mendeliome v1.4816 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.765 LMAN2L Zornitza Stark Publications for gene: LMAN2L were set to PMID: 31020005; 26566883
Intellectual disability syndromic and non-syndromic v1.764 LMAN2L Zornitza Stark Classified gene: LMAN2L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.764 LMAN2L Zornitza Stark Gene: lman2l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Added comment: Upgrade AR GDA to Green given the reports of biallelic variants in affected individuals.
No new reports supportive of the AD GDA association.

PMID: 40221759 and 37667433 report two additional probands presenting with ID, global DD and other neurodevelopmental features. Both probands were compound heterozygous.; Changed rating: GREEN; Changed publications: 40221759, 37667433
Mendeliome v1.4815 LMAN2L Zornitza Stark Publications for gene: LMAN2L were set to 31020005; 26566883
Mendeliome v1.4814 LMAN2L Zornitza Stark Classified gene: LMAN2L as Green List (high evidence)
Mendeliome v1.4814 LMAN2L Zornitza Stark Gene: lman2l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 NPRL2 Zornitza Stark Marked gene: NPRL2 as ready
Intellectual disability syndromic and non-syndromic v1.763 NPRL2 Zornitza Stark Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4813 ATG12 Zornitza Stark Marked gene: ATG12 as ready
Mendeliome v1.4813 ATG12 Zornitza Stark Gene: atg12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Zornitza Stark Marked gene: ATG12 as ready
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Zornitza Stark Gene: atg12 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark Marked gene: NSMCE3 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark Marked gene: NSMCE3 as ready
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.147 NSMCE3 Zornitza Stark Publications for gene: NSMCE3 were set to 27427983
Combined Immunodeficiency v1.146 NSMCE3 Zornitza Stark Classified gene: NSMCE3 as Green List (high evidence)
Combined Immunodeficiency v1.146 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.145 NSMCE3 Zornitza Stark edited their review of gene: NSMCE3: Changed rating: GREEN
Combined Immunodeficiency v1.145 NSMCE3 Zornitza Stark edited their review of gene: NSMCE3: Added comment: Total of five families with severe childhood‑onset lung disease, variable combined T‑cell/B‑cell immunodeficiency and chromosome breakage. Three of these families were homozygous for the same missense variant, p.(Leu264Phe) - articles below.

PMID: 40728043 | 1x paediatric case of lethal lung disease no history of failure to thrive, recurrent infections, or immunodeficiency. Compound heterozygous for p.(Lys260Ter) and p.(Pro105Ser).

PMID: 33741030 | five patients from two unrelated families with biallelic NSMCE3 missense variants did not reveal immunodeficiency; though all presented with severe lung disease. All five patients were homozygous for a single missense variant in NSMCE3, p.(Leu264Phe), that was previously identified in the initial report (PMID: 27427983).

PMID: 27427983 | 2x unrelated families with chromosome breakage syndrome with severe lung disease, 1xhom for p.(Leu264Phe), the other cHet for different missense.; Changed publications: 27427983, 40728043, 33741030
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 Zornitza Stark Copied gene NSMCE3 from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.11 NSMCE3 Zornitza Stark gene: NSMCE3 was added
gene: NSMCE3 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NSMCE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE3 were set to 27427983; 40728043; 33741030
Phenotypes for gene: NSMCE3 were set to Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241
Chromosome Breakage Disorders v1.25 Zornitza Stark Copied gene NSMCE3 from panel Mendeliome
Chromosome Breakage Disorders v1.25 NSMCE3 Zornitza Stark gene: NSMCE3 was added
gene: NSMCE3 was added to Chromosome Breakage Disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NSMCE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE3 were set to 27427983; 40728043; 33741030
Phenotypes for gene: NSMCE3 were set to Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241
Mendeliome v1.4813 NSMCE3 Zornitza Stark Publications for gene: NSMCE3 were set to 27427983
Mendeliome v1.4812 NSMCE3 Zornitza Stark Classified gene: NSMCE3 as Green List (high evidence)
Mendeliome v1.4812 NSMCE3 Zornitza Stark Gene: nsmce3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.763 Sangavi Sivagnanasundram Copied gene ATG12 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.763 ATG12 Sangavi Sivagnanasundram gene: ATG12 was added
gene: ATG12 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4811 ATG12 Sangavi Sivagnanasundram edited their review of gene: ATG12: Changed phenotypes: ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4811 ATG12 Sangavi Sivagnanasundram Phenotypes for gene: ATG12 were changed from Neurodevelopmental disorder, MONDO:0700092 to ATG12-related neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4810 ATG12 Sangavi Sivagnanasundram Classified gene: ATG12 as Green List (high evidence)
Mendeliome v1.4810 ATG12 Sangavi Sivagnanasundram Gene: atg12 has been classified as Green List (High Evidence).
Mendeliome v1.4809 ATG12 Sangavi Sivagnanasundram gene: ATG12 was added
gene: ATG12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: ATG12 was set to GREEN
Added comment: PMID 41895291 reports six individuals from five unrelated families with biallelic loss-of-function ATG12 variants causing a childhood‑onset neurodevelopmental disorder characterized by developmental delay, intellectual disability, congenital ataxia, hypotonia, seizures and cerebellar vermis hypoplasia. The paper reports on functional evidence supportive of pathogenicity.

Note: one of the reported variants (c.363+3A>T) had an FAF of 0.01706% in gnomAD and hasn't been reported in any other affected individuals.
Sources: Literature
Speech apraxia v1.31 FOXP1 Hali Van Niel gene: FOXP1 was added
gene: FOXP1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to (PMID: 41530369; 34109629; 39931922)
Phenotypes for gene: FOXP1 were set to intellectual disability-severe speech delay-mild dysmorphism syndrome (MONDO: 0013352)
Review for gene: FOXP1 was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369)

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: AMBER; Mode of pathogenicity: None; Publications: (PMID: 41530369, 39931922); Phenotypes: intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 GNAI1 Hali Van Niel gene: GNAI1 was added
gene: GNAI1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: GNAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAI1 were set to PMID: 41530369; 39931922; 33473207
Phenotypes for gene: GNAI1 were set to neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities (MIM#619854)
Review for gene: GNAI1 was set to AMBER
Added comment: One reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype has variable expressivity ranging from mild to severe (PMID: 33473207)
Sources: Expert List, Literature
Mendeliome v1.4808 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Mendeliome v1.4808 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4808 MT-TQ Zornitza Stark Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700; 38730005; 32588991
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark Marked gene: FOXJ3 as ready
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.413 Zornitza Stark Copied gene FOXJ3 from panel Mendeliome
Genetic Epilepsy v1.413 FOXJ3 Zornitza Stark gene: FOXJ3 was added
gene: FOXJ3 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FOXJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ3 were set to 41803108
Phenotypes for gene: FOXJ3 were set to Focal epilepsy, MONDO:0005384, FOXJ3-related
Mendeliome v1.4807 FOXJ3 Zornitza Stark Marked gene: FOXJ3 as ready
Mendeliome v1.4807 FOXJ3 Zornitza Stark Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Zornitza Stark Marked Region: ISCA-46303-Loss as ready
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Clefting disorders v0.318 ISCA-46303-Loss Zornitza Stark Marked Region: ISCA-46303-Loss as ready
Clefting disorders v0.318 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Congenital Heart Defect v0.538 FLNA Zornitza Stark Marked gene: FLNA as ready
Congenital Heart Defect v0.538 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Congenital Heart Defect v0.538 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to cardiac valvular dysplasia, X-linked MONDO:0010753
Congenital Heart Defect v0.537 FLNA Zornitza Stark Publications for gene: FLNA were set to
Congenital Heart Defect v0.536 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Fetal anomalies v1.570 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from ReNU syndrome (MIM# 620851), AD to ReNU syndrome (MIM# 620851)
Fetal anomalies v1.569 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Fetal anomalies v1.569 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Speech apraxia v1.31 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Speech apraxia v1.31 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Speech apraxia v1.31 CAMTA1 Zornitza Stark Classified gene: CAMTA1 as Green List (high evidence)
Speech apraxia v1.31 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Green List (High Evidence).
Speech apraxia v1.30 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Speech apraxia v1.30 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence).
Speech apraxia v1.30 EHMT1 Zornitza Stark Classified gene: EHMT1 as Green List (high evidence)
Speech apraxia v1.30 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Hali Van Niel changed review comment from: Three reported individuals with CAS in LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature; to: Three reported individuals with CAS and LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Cardiomyopathy_Paediatric v0.231 Zornitza Stark removed gene:NDUFA5 from the panel
Intellectual disability syndromic and non-syndromic v1.762 Zornitza Stark removed gene:NDUFA5 from the panel
Speech apraxia v1.29 EHMT1 Hali Van Niel gene: EHMT1 was added
gene: EHMT1 was added to Speech apraxia. Sources: Expert List
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHMT1 were set to PMID: 41530369; PMID: 38290825
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1 (MIM#610253)
Review for gene: EHMT1 was set to GREEN
Added comment: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369)

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Mitochondrial disease v1.18 NDUFA5 Zornitza Stark Phenotypes for gene: NDUFA5 were changed from Complex I deficiency to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark reviewed gene: NDUFA5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, NDUFA5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4807 NDUFA5 Zornitza Stark Marked gene: NDUFA5 as ready
Mendeliome v1.4807 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Mendeliome v1.4807 NDUFA5 Zornitza Stark Phenotypes for gene: NDUFA5 were changed from Complex I deficiency to Mitochondrial disease, MONDO:0044970, NDUFA5-related
Mendeliome v1.4806 NDUFA5 Zornitza Stark reviewed gene: NDUFA5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, NDUFA5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.761 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.761 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Cardiomyopathy_Paediatric v0.230 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.230 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Mendeliome v1.4806 Zornitza Stark Copied gene NDUFA5 from panel Mitochondrial disease
Mendeliome v1.4806 NDUFA5 Zornitza Stark gene: NDUFA5 was added
gene: NDUFA5 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark Classified gene: NDUFA5 as Green List (high evidence)
Mitochondrial disease v1.17 NDUFA5 Zornitza Stark Gene: ndufa5 has been classified as Green List (High Evidence).
Speech apraxia v1.29 EBF3 Hali Van Niel reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41530369, PMID: 39931922; Phenotypes: hypotonia, ataxia, and delayed development syndrome (MIM#617330); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v1.29 CAMTA1 Hali Van Niel gene: CAMTA1 was added
gene: CAMTA1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to PMID: 41530369; PMID: 39931922; PMID: 33131045
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioural abnormalities (MIM#614756)
Review for gene: CAMTA1 was set to GREEN
Added comment: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature
Skeletal Dysplasia_Fetal v0.250 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Skeletal Dysplasia_Fetal v0.250 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Skeletal Dysplasia_Fetal. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Skeletal dysplasia v0.434 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Skeletal dysplasia v0.434 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Fetal anomalies v1.568 Zornitza Stark Copied gene WDHD1 from panel Mendeliome
Fetal anomalies v1.568 WDHD1 Zornitza Stark gene: WDHD1 was added
gene: WDHD1 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Mendeliome v1.4805 WDHD1 Zornitza Stark Marked gene: WDHD1 as ready
Mendeliome v1.4805 WDHD1 Zornitza Stark Gene: wdhd1 has been classified as Green List (High Evidence).
Mendeliome v1.4805 WDHD1 Zornitza Stark Classified gene: WDHD1 as Green List (high evidence)
Mendeliome v1.4805 WDHD1 Zornitza Stark Gene: wdhd1 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.41 Zornitza Stark Added reviews for gene CD3D from panel Severe Combined Immunodeficiency
Genomic newborn screening: ICoNS v0.40 Zornitza Stark Copied gene ARSB from panel Craniosynostosis
Genomic newborn screening: ICoNS v0.40 ARSB Zornitza Stark gene: ARSB was added
gene: ARSB was added to Genomic newborn screening: ICoNS. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSB were set to Mucopolysaccharidosis VI (MPS6, MIM# 253200
Hypertrophic cardiomyopathy v1.26 POPDC2 Zornitza Stark Classified gene: POPDC2 as Green List (high evidence)
Hypertrophic cardiomyopathy v1.26 POPDC2 Zornitza Stark Gene: popdc2 has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Speech apraxia v1.29 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Speech apraxia v1.29 CACNA1A Zornitza Stark Classified gene: CACNA1A as Green List (high evidence)
Speech apraxia v1.29 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Speech apraxia v1.28 CACNA1A Hali Van Niel gene: CACNA1A was added
gene: CACNA1A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to (PMID: 41530369); (PMID: 39931922)
Phenotypes for gene: CACNA1A were set to CACNA1A-related complex neurodevelopmental disorder (MONDO:0100254)
Review for gene: CACNA1A was set to GREEN
Added comment: Three reported individuals with CAS in LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark Marked gene: CAPZA1 as ready
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.150 Zornitza Stark Copied gene CAPZA1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.150 CAPZA1 Zornitza Stark gene: CAPZA1 was added
gene: CAPZA1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CAPZA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPZA1 were set to 41858859
Phenotypes for gene: CAPZA1 were set to Infertility disorder, MONDO:0005047
Mendeliome v1.4804 CAPZA1 Zornitza Stark Marked gene: CAPZA1 as ready
Mendeliome v1.4804 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4804 CAPZA1 Zornitza Stark Classified gene: CAPZA1 as Amber List (moderate evidence)
Mendeliome v1.4804 CAPZA1 Zornitza Stark Gene: capza1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4803 CAPZA1 Zornitza Stark gene: CAPZA1 was added
gene: CAPZA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPZA1 were set to 41858859
Phenotypes for gene: CAPZA1 were set to Infertility disorder, MONDO:0005047
Review for gene: CAPZA1 was set to AMBER
Added comment: PMID 41858859 reports four individuals from different families with autosomal recessive asthenozoospermia due to a homozygous missense variant c.11T>C (p.Phe4Ser) in CAPZA1. Segregation analysis confirms biallelic inheritance, and mouse knockout and in‑vitro assays demonstrate reduced CAPZA1 protein and disrupted sperm flagellar structure, providing supportive functional evidence.
Sources: Literature
Brain Calcification v2.9 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Brain Calcification v2.8 XPR1 Zornitza Stark edited their review of gene: XPR1: Added comment: PMID 41834789 reports 13 affected individuals from 4 consanguineous families with a homozygous loss‑of‑function missense variant (c.1811G>A; p.Arg604Gln) causing neonatal‑onset severe multisystem disease (brain calcifications, developmental delay, hypophosphataemia, cardiopulmonary involvement). Likely founder variant. Remains to be seen whether the biallelic disease relates specifically to this variant. Amber for this association -- caution with other variants warranted.; Changed publications: 25938945, 41834789; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4802 XPR1 Zornitza Stark Publications for gene: XPR1 were set to 25938945
Mendeliome v1.4801 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4800 XPR1 Zornitza Stark edited their review of gene: XPR1: Added comment: PMID 41834789 reports 13 affected individuals from 4 consanguineous families with a homozygous loss‑of‑function missense variant (c.1811G>A; p.Arg604Gln) causing neonatal‑onset severe multisystem disease (brain calcifications, developmental delay, hypophosphataemia, cardiopulmonary involvement).

Likely founder variant. Remains to be seen whether the biallelic disease relates specifically to this variant. Amber for this association -- caution with other variants warranted.; Changed publications: 41834789; Changed phenotypes: Basal ganglia calcification, idiopathic, 6, MONDO:0014628; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v1.54 Sarah Milton Copied Region SOX9 upstream regulatory region gain from panel Mendeliome
Differences of Sex Development v1.54 SOX9 upstream regulatory region gain Sarah Milton Region: SOX9 upstream regulatory region gain was added
Region: SOX9 upstream regulatory region gain was added to Differences of Sex Development. Sources: Literature
regulatory region tags were added to Region: SOX9 upstream regulatory region gain.
Mode of inheritance for Region: SOX9 upstream regulatory region gain was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: SOX9 upstream regulatory region gain were set to PMID: 37551848; 30552336; 31661700
Phenotypes for Region: SOX9 upstream regulatory region gain were set to 46XX sex reversal 2, MIM#278850
Penetrance for Region: SOX9 upstream regulatory region gain were set to Incomplete
Mendeliome v1.4800 SOX9 upstream regulatory region gain Sarah Milton changed review comment from: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature; to: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region affecting XYSR enhancer however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature
Mendeliome v1.4800 SOX9 upstream regulatory region gain Sarah Milton Region: SOX9 upstream regulatory region gain was added
Region: SOX9 upstream regulatory region gain was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: SOX9 upstream regulatory region gain.
Mode of inheritance for Region: SOX9 upstream regulatory region gain was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: SOX9 upstream regulatory region gain were set to PMID: 37551848; 30552336; 31661700
Phenotypes for Region: SOX9 upstream regulatory region gain were set to 46XX sex reversal 2, MIM#278850
Penetrance for Region: SOX9 upstream regulatory region gain were set to Incomplete
Review for Region: SOX9 upstream regulatory region gain was set to GREEN
Added comment: The upstream regulatory region of SOX9 has been demonstrated to have key roles in transcription factor binding including binding of SRY.

Increased dosage of this agenic region has been demonstrated in a number of individuals to result in 46XX sex reversal with a varying phenotype from DSD to phenotypic male.

The coordinates used in this entry are the minimal critical region however reported duplications range from 3.7kb to 780kb.
Incomplete penetrance has been observed.

Supportive functional studies in the form of mouse models and luciferase reporter assays have been published.

Note: Duplications of this region in 46,XY individuals don't result in a phenotype. Refer to ISCA-46303 loss entry.
Sources: Literature
Congenital Heart Defect v0.535 FLNA Sangavi Sivagnanasundram reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29334594, 20301392; Phenotypes: cardiac valvular dysplasia, X-linked MONDO:0010753; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v1.53 ISCA-46303-Loss Sarah Milton Publications for Region: ISCA-46303-Loss were changed from PMID: 24934569, 26663529, 19234473, 26152199, 30552336 to PMID: 41272840, 24934569, 26663529, 19234473, 26152199, 30552336
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen
Clefting disorders v0.318 ISCA-46303-Loss Sarah Milton Phenotypes for Region: ISCA-46303-Loss were changed from to Pierre Robin syndrome MIM#261800
Tag regulatory region was added to Region: ISCA-46303-Loss.
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.158 ISCA-46303-Loss Sarah Milton Phenotypes for Region: ISCA-46303-Loss were changed from to Campomelic dysplasia MIM#114290, Acampomelic campomelic dysplasia MIM#114290, 46XY sex reversal 10 MIM#616425, Pierre Robin syndrome MIM#261800
Publications for Region: ISCA-46303-Loss were changed from PMID: 24934569, 26663529, 19234473, 26152199, 30552336 to PMID: 41272840. 24934569, 26663529, 19234473, 26152199, 30552336
Tag regulatory region was added to Region: ISCA-46303-Loss.
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 have been associated with Pierre Robin syndrome, campomelic dysplasia, acampomelic dysplasia as well as 46,XY sex reversal.

This region has been curated by Clingen for the Pierre Robin syndrome phenotype and has been called HI3. Coordinates were based on the largest region found in affected individuals.

There are a number of enhancer elements within this region of which there are proposed to be four clusters: a proximal cluster between 50-375 kb, a sex-determining interval RevSex region between 517-595 kb, a distal cluster between 601 and 932 kb, and a PRS cluster between 1.03–1.26 Mb. Defining genotype phenotype has not been conclusively established within the literature in this region however there are some noted correlations.

Incomplete penetrance has been noted for the 46,XY sex reversal with approx 75% of individuals with deletions in this region demonstrating a DSD phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia. Note that loss of SOX9 function does not cause sex reversal in individuals with a 46,XX karyotype. See additional entry for gain of this region.

Sources: ClinGen
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton Classified Region: ISCA-46303-Loss as Green List (high evidence)
Common deletion and duplication syndromes v0.157 ISCA-46303-Loss Sarah Milton Region: isca-46303-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v0.156 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton Classified Region: ISCA-46303-Loss as Green List (high evidence)
Clefting disorders v0.317 ISCA-46303-Loss Sarah Milton Region: isca-46303-loss has been classified as Green List (High Evidence).
Clefting disorders v0.316 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia..
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia.
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Incomplete penetrance has been noted with approx 75% of individuals with deletions in this region demonstrating a 46,XY sex reversal phenotype ranging from ambiguous genitalia to typical female external genitalia..
Sources: ClinGen
Differences of Sex Development v1.52 ISCA-46303-Loss Sarah Milton changed review comment from: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen; to: Deletion of the upstream enhancer of SOX9 has been shown to be associated with Pierre Robin syndrome in a number of affected individuals and this region has been curated by Clingen to be HI3. Coordinates were based on the largest region found in affected individuals.

It should be noted deletions of upstream enhancer elements of SOX9 of different sizes have also been associated with male to female sex reversal. Exact coordinates and critical regions are still being defined in the literature.
Sources: ClinGen
Clefting disorders v0.316 TBX15 Zornitza Stark Marked gene: TBX15 as ready
Clefting disorders v0.316 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Clefting disorders v0.316 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from COUSIN SYNDROME to Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845; Cleft palate, MONDO:0016064, TBX15-related
Clefting disorders v0.315 TBX15 Zornitza Stark Publications for gene: TBX15 were set to
Clefting disorders v0.314 TBX15 Zornitza Stark Mode of inheritance for gene: TBX15 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting disorders v0.313 TBX15 Zornitza Stark Classified gene: TBX15 as Green List (high evidence)
Clefting disorders v0.313 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Clefting disorders v0.312 TBX15 Zornitza Stark reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068278, 24039145, 41904889, 40693652, 36124393; Phenotypes: Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845, Cleft palate, MONDO:0016064, TBX15-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4799 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from Cousin syndrome, MIM# 260660 to Cousin syndrome, MIM# 260660; Cleft palate, MONDO:0016064, TBX15-related
Mendeliome v1.4798 TBX15 Zornitza Stark Publications for gene: TBX15 were set to 19068278; 24039145
Mendeliome v1.4797 TBX15 Zornitza Stark Mode of inheritance for gene: TBX15 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4796 TBX15 Zornitza Stark edited their review of gene: TBX15: Changed publications: 41904889, 40693652, 36124393, 40693652
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.; to: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.

PMID 40693652 reports a further individual with biallelic TBX15 missense (c.709A>G) causing a milder form of Cousin syndrome.
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: Cleft palate, multiple skeletal abnormalities. Three families reported.; to: Cousin syndrome: Cleft palate, multiple skeletal abnormalities. Three families reported.
Mendeliome v1.4796 TBX15 Zornitza Stark changed review comment from: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.; to: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.

Evidence for mono allelic is Amber, given borderline number of families and postulated association with a relatively common phenotype, which is typically not monogenic.
Mendeliome v1.4796 TBX15 Zornitza Stark edited their review of gene: TBX15: Added comment: PMID 36124393 reports 2 individuals from 2 unrelated families with de novo heterozygous TBX15 missense (c.370A>C, c.1549C>A) causing soft palate dysplasia; PMID 41904889 reports 3 individuals from 1 family with heterozygous TBX15 nonsense (c.1231C>T) co‑segregating with submucous cleft palate. All heterozygous variants are loss‑of‑function, supported by luciferase reporter loss, ChIP loss of promoter binding, and immunofluorescence mis‑localisation.; Changed publications: 41904889, 40693652, 36124393; Changed phenotypes: Pelviscapular dysplasia (Cousin syndrome), MONDO:0009845, Cleft palate, MONDO:0016064, TBX15-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.760 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Intellectual disability syndromic and non-syndromic v1.759 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.758 SLC20A2 Zornitza Stark Classified gene: SLC20A2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.758 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.757 SLC20A2 Zornitza Stark changed review comment from: Progressive neurological condition, ID is not part of the phenotype.; to: Mono-allelic association: Progressive neurological condition, ID is not part of the phenotype.
Intellectual disability syndromic and non-syndromic v1.757 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

Gene is classically associated with a milder mono-allelic disorder, which typically does not involve ID.; Changed rating: AMBER; Changed publications: 41458256, 35881308; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v2.8 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463
Brain Calcification v2.7 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Brain Calcification v2.6 SLC20A2 Zornitza Stark changed review comment from: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; to: Bi-allelic association:

PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.
Brain Calcification v2.6 SLC20A2 Zornitza Stark changed review comment from: Over 50 families reported. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache.; to: Mono-allelic association: Over 50 families reported. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache.
Brain Calcification v2.6 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; Changed publications: 22327515, 23334463, 24209445, 23437308, 32705272, 27943094; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Classified gene: SLC20A2 as Amber List (moderate evidence)
Genetic Epilepsy v1.412 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.411 SLC20A2 Zornitza Stark gene: SLC20A2 was added
gene: SLC20A2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC20A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC20A2 were set to 41458256; 35881308
Phenotypes for gene: SLC20A2 were set to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Review for gene: SLC20A2 was set to AMBER
Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

Gene is classically associated with a milder mono-allelic disorder, which typically does not involve seizures.
Sources: Literature
Mendeliome v1.4796 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463; 24209445; 23437308; 32705272; 27943094
Mendeliome v1.4795 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4794 SLC20A2 Zornitza Stark edited their review of gene: SLC20A2: Added comment: PMID 41458256: Reports a single individual a homozygous nonsense SLC20A2 variant presenting with infantile primary familial brain calcification, cerebral arterial vasculopathy and ischaemic stroke. Individual exhibited seizures, hypotonia, poor feeding, and extensive ischaemic changes.

PMID 35881308: reports two siblings from a consanguineous Turkish family with a homozygous splice‑site loss‑of‑function variant NM_006749.5:c.1794+1G>A. The affected children presented with severe paediatric‑onset features resembling congenital CMV infection: growth retardation, bilateral cataracts, microcephaly, seizures, cerebral atrophy, corpus callosum hypoplasia and brain microcalcifications.

PMID 34267336 reports a consanguineous family including a 55‑year‑old woman homozygous for the missense variant c.211C>T (p.Arg71Cys) who had extensive basal ganglia calcifications, psychiatric manifestations and progressive Parkinsonism.; Changed publications: 22327515, 23334463, 41458256, 35881308, 34267336; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.149 PADI6 Zornitza Stark changed review comment from: Inheritance is biallelic: PMID 34987164 reports 13 unrelated families (14 patients) with biallelic loss‑of‑function PADI6 variants causing early embryonic arrest (2‑7 cell stage) and female infertility.; to: PMID 34987164 reports 13 unrelated families (14 patients) with biallelic loss‑of‑function PADI6 variants causing early embryonic arrest (2‑7 cell stage) and female infertility.
Infertility and Recurrent Pregnancy Loss v1.149 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 29693651; 33583041; 33221824; 27730629; 27545678
Infertility and Recurrent Pregnancy Loss v1.148 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164; Phenotypes: Oocyte/zygote/embryo maturation arrest 16, #MIM 617234; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v1.11 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 27545678; 33221824; 32928291
Imprinting disorders v1.10 PADI6 Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v1.9 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164, 35296332; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4794 PADI6 Zornitza Stark Publications for gene: PADI6 were set to 29693651; 33583041; 32928291; 33221824; 27545678
Mendeliome v1.4793 PADI6 Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4792 PADI6 Zornitza Stark reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: 34987164, 35296332; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4792 KDM1A Zornitza Stark Phenotypes for gene: KDM1A were changed from Cleft palate, psychomotor retardation, and distinctive facial features 616728; Multiple myeloma to Cleft palate, psychomotor retardation, and distinctive facial features 616728; Multiple myeloma; ACTH-independent macronodular adrenal hyperplasia 3, MONDO:0700299
Mendeliome v1.4791 KDM1A Zornitza Stark Publications for gene: KDM1A were set to 29559475; 27094131
Mendeliome v1.4790 Zornitza Stark Added reviews for gene KDM1A from panel Primary nodular adrenocortical disease
Growth failure v1.104 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Growth failure v1.103 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.757 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Intellectual disability syndromic and non-syndromic v1.756 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.428 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Microcephaly v1.427 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4789 MAU2 Zornitza Stark Phenotypes for gene: MAU2 were changed from Cornelia de Lange syndrome MONDO:0016033, MAU2-related to Cornelia de Lange syndrome 7, MIM# 621570
Mendeliome v1.4788 MAU2 Zornitza Stark reviewed gene: MAU2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 7, MIM# 621570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.55 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Red cell disorders v1.54 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Red cell disorders v1.53 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Red cell disorders v1.53 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Red cell disorders v1.52 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374; Changed phenotypes: Diamond-Blackfan anaemia 16, MIM# 617408
Diamond Blackfan anaemia v1.20 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Mendeliome v1.4788 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Mendeliome v1.4787 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Mendeliome v1.4787 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4786 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374
Bone Marrow Failure v1.144 RPL27 Zornitza Stark Phenotypes for gene: RPL27 were changed from Diamond-Blackfan anemia 16, MIM# 617408 to Diamond-Blackfan anaemia 16, MIM# 617408
Bone Marrow Failure v1.143 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Bone Marrow Failure v1.142 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Bone Marrow Failure v1.142 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.141 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 25424902, 38988374; Changed phenotypes: Diamond-Blackfan anaemia 16, MIM# 617408
Diamond Blackfan anaemia v1.19 RPL27 Zornitza Stark Publications for gene: RPL27 were set to 25424902
Diamond Blackfan anaemia v1.18 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
Diamond Blackfan anaemia v1.18 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v1.17 RPL27 Zornitza Stark edited their review of gene: RPL27: Added comment: PMID 38988374 reports an individual from a second unrelated family with a de novo splice‑site RPL27 variant and a DBA phenotype.; Changed rating: AMBER; Changed publications: 38988374; Changed phenotypes: Diamond-Blackfan anemia 16, MONDO:0044309; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4786 RPL4 Zornitza Stark Marked gene: RPL4 as ready
Mendeliome v1.4786 RPL4 Zornitza Stark Gene: rpl4 has been classified as Red List (Low Evidence).
Mendeliome v1.4786 Zornitza Stark Copied gene RPL4 from panel Diamond Blackfan anaemia
Mendeliome v1.4786 RPL4 Zornitza Stark gene: RPL4 was added
gene: RPL4 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL4 were set to 30213830
Phenotypes for gene: RPL4 were set to Diamond Blackfan anaemia, MONDO:0015253, RPL4-related
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark Marked gene: RPL4 as ready
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark Gene: rpl4 has been classified as Red List (Low Evidence).
Diamond Blackfan anaemia v1.17 RPL4 Zornitza Stark gene: RPL4 was added
gene: RPL4 was added to Diamond Blackfan anaemia. Sources: Literature
Mode of inheritance for gene: RPL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL4 were set to 30213830
Phenotypes for gene: RPL4 were set to Diamond Blackfan anaemia, MONDO:0015253, RPL4-related
Review for gene: RPL4 was set to RED
Added comment: PMID 30213830 reports a single individual with a de novo heterozygous splice‑site RPL4 variant presenting with Diamond‑Blackfan anemia‑like syndrome (macrocytic anemia, growth retardation, cleft lip, low‑set ears, toe anomalies, developmental delay, short stature, hearing loss). Functional assays show aberrant splicing, impaired ribosomal RNA processing, and somatic reversion via mosaic UPD15q, supporting loss‑of‑function haploinsufficiency.
Sources: Literature
Prepair 500+ v2.1 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Prepair 500+ v2.0 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v2.17 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Retinitis pigmentosa 59, MIM#613861; Congenital disorder of glycosylation, type 1bb, MIM# 621567
Prepair 1000+ v2.16 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.246 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Retinitis pigmentosa v0.245 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4785 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Developmental delay and seizures with or without movement abnormalities, MIM#617836; Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Developmental delay and seizures with or without movement abnormalities, MIM#617836; Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4784 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM#617836, Congenital disorder of glycosylation, type 1bb, MIM# 621567
Congenital Disorders of Glycosylation v1.86 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Congenital disorder of glycosylation, type 1bb, MIM# 613861 to Congenital disorder of glycosylation, type 1bb, MIM# 621567
Congenital Disorders of Glycosylation v1.85 DHDDS Zornitza Stark edited their review of gene: DHDDS: Changed phenotypes: Congenital disorder of glycosylation, type 1bb, MIM# 621567
Mendeliome v1.4784 HAT1 Monique Dunstan Tag SV/CNV was removed from gene: HAT1.
Tag STR was removed from gene: HAT1.
Tag refuted was removed from gene: HAT1.
Hereditary Pigmentary Disorders v1.5 ABCB6 Katrina Bell Deleted their review
Hereditary Pigmentary Disorders v1.5 ABCB6 Katrina Bell Deleted their comment
Stroke v1.48 ABCA1 Katrina Bell Deleted their review
Mendeliome v1.4784 HAT1 Monique Dunstan All sources for gene: HAT1 were removed
Mendeliome v1.4783 ABCA1 Katrina Bell Tag somatic was removed from gene: ABCA1.
Tag 5'UTR was removed from gene: ABCA1.
Mendeliome v1.4783 ABCA1 Katrina Bell Deleted their review
Mendeliome v1.4783 ABCA1 Katrina Bell Deleted their comment
Mendeliome v1.4783 ALG5 Monique Dunstan Deleted their review
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their review
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their comment
Mendeliome v1.4783 HAT1 Monique Dunstan Deleted their comment
Mendeliome v1.4783 ABCB6 Katrina Bell Deleted their review
Mendeliome v1.4783 ABCB6 Katrina Bell Deleted their comment
Intellectual disability syndromic and non-syndromic v1.756 CRMP1 Zornitza Stark Phenotypes for gene: CRMP1 were changed from neurodevelopmental disorder, MONDO:0700092, CRMP2-related to neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Intellectual disability syndromic and non-syndromic v1.755 CRMP1 Zornitza Stark edited their review of gene: CRMP1: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Mendeliome v1.4783 CRMP1 Zornitza Stark Phenotypes for gene: CRMP1 were changed from neurodevelopmental disorder, MONDO:0700092, CRMP2-related to neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Mendeliome v1.4782 CRMP1 Zornitza Stark edited their review of gene: CRMP1: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, CRMP1-related
Genetic Epilepsy v1.410 RYR3 Lilian Downie Added comment: Comment on mode of inheritance: Limited by clingen for AD epilepsy, not considered for AR by ClinGen.
All of the recessive DEE patients are from the 2 Chinese papers PMID 39840699, PMID: 29667327. Amber for AR DEE
Genetic Epilepsy v1.410 RYR3 Lilian Downie Mode of inheritance for gene: RYR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.409 RYR3 Lucy Spencer reviewed gene: RYR3: Rating: AMBER; Mode of pathogenicity: None; Publications: 39220738, 39840699, 25262651, 29667327, 31230720; Phenotypes: Developmental and epileptic encephalopathy MONDO:0100620, RYR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.249 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Skeletal Dysplasia_Fetal v0.248 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.248 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Fetal anomalies v1.567 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Fetal anomalies v1.566 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Fetal anomalies v1.566 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.247 Zornitza Stark Added reviews for gene GNPNAT1 from panel Skeletal dysplasia
Fetal anomalies v1.565 Zornitza Stark Added reviews for gene GNPNAT1 from panel Skeletal dysplasia
Skeletal dysplasia v0.433 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 32591345
Skeletal dysplasia v0.432 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Skeletal dysplasia v0.432 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Mendeliome v1.4782 GNPNAT1 Zornitza Stark Publications for gene: GNPNAT1 were set to 32591345
Mendeliome v1.4781 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Green List (high evidence)
Mendeliome v1.4781 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Green List (High Evidence).
Mendeliome v1.4780 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to 30665704
Mendeliome v1.4779 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Green List (high evidence)
Mendeliome v1.4779 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.77 GAS2L2 Zornitza Stark Publications for gene: GAS2L2 were set to 30665704
Ciliary Dyskinesia v1.76 GAS2L2 Zornitza Stark Classified gene: GAS2L2 as Green List (high evidence)
Ciliary Dyskinesia v1.76 GAS2L2 Zornitza Stark Gene: gas2l2 has been classified as Green List (High Evidence).
Fetal anomalies v1.564 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Fetal anomalies v1.564 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note discrepancy in head size and predominance of missense variants, hence retain Amber rating.
Fetal anomalies v1.564 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.564 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 30266093; 25388005; 30214071
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note discordant phenotype in relation to head size and predominance of missense variants, hence retain Amber rating
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.755 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 25388005; 30214071
Intellectual disability syndromic and non-syndromic v1.754 Zornitza Stark Added reviews for gene FRMD4A from panel Mendeliome
Fetal anomalies v1.563 Zornitza Stark Added reviews for gene FRMD4A from panel Mendeliome
Mendeliome v1.4778 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Mendeliome v1.4778 FRMD4A Zornitza Stark Added comment: Comment when marking as ready: Note phenotype is discordant in terms of head circumference and also evidence based on missense variants, retain Amber rating.
Mendeliome v1.4778 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4778 FRMD4A Zornitza Stark Publications for gene: FRMD4A were set to 25388005; 30214071
Fetal anomalies v1.562 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Fetal anomalies v1.561 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Fetal anomalies v1.561 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Fetal anomalies v1.560 Zornitza Stark Added reviews for gene FAM92A from panel Mendeliome
Polydactyly v0.303 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Polydactyly v0.302 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Polydactyly v0.302 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Mendeliome v1.4777 FAM92A Zornitza Stark Publications for gene: FAM92A were set to 30395363
Mendeliome v1.4776 FAM92A Zornitza Stark Classified gene: FAM92A as Green List (high evidence)
Mendeliome v1.4776 FAM92A Zornitza Stark Gene: fam92a has been classified as Green List (High Evidence).
Mendeliome v1.4775 FOXJ3 Rylee Peters Classified gene: FOXJ3 as Amber List (moderate evidence)
Mendeliome v1.4775 FOXJ3 Rylee Peters Gene: foxj3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4774 PLEKHM2 Rylee Peters Phenotypes for gene: PLEKHM2 were changed from Dilated cardiomyopathy MONDO:0005021 to Dilated cardiomyopathy, MONDO:0005021, PLEKHM2-related
Mendeliome v1.4773 PLEKHM2 Rylee Peters Publications for gene: PLEKHM2 were set to 35862026; 26464484; 38942823; 38490981; 37349842
Mendeliome v1.4772 MT-TQ Rylee Peters Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Mendeliome v1.4771 TRU-TCA1-1 Zornitza Stark Classified gene: TRU-TCA1-1 as Amber List (moderate evidence)
Mendeliome v1.4771 TRU-TCA1-1 Zornitza Stark Gene: tru-tca1-1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4770 SCP2 Zornitza Stark Phenotypes for gene: SCP2 were changed from Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724 to Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724; Craniofacial microsomia, MONDO:0015397, SCP2-related
Mendeliome v1.4769 SCP2 Zornitza Stark Publications for gene: SCP2 were set to 16685654; 26497993
Mendeliome v1.4768 SCP2 Zornitza Stark Mode of inheritance for gene: SCP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Marked gene: NLGN3 as ready
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.137 NLGN3 Chirag Patel Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425; Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4767 SCP2 Zornitza Stark edited their review of gene: SCP2: Added comment: PMID 39941065 reports 2 individuals from 2 unrelated families with de novo heterozygous missense CTDSP2 (c.332C>A, p.T111N) variants presenting with hemifacial microsomia (unilateral facial hypoplasia, ear malformations, mandibular underdevelopment). Zebrafish ctdsp2 knockout recapitulates the craniofacial phenotype and rescue by wild‑type ctdsp2 mRNA or tp53 knockout restores normal cartilage, providing functional support.; Changed publications: 26497993, 39941065; Changed phenotypes: Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724, Craniofacial microsomia, MONDO:0015397, SCP2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.136 NLGN3 Chirag Patel Mode of inheritance for gene: NLGN3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypogonadotropic hypogonadism v0.135 NLGN3 Chirag Patel Classified gene: NLGN3 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.135 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.134 Chirag Patel Added reviews for gene NLGN3 from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel reviewed gene: NLGN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 36810932; Phenotypes: Hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Marked gene: NLGN3 as ready
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.226 NLGN3 Chirag Patel Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425; hypogonadotropic hypogonadism MONDO:0018555
Pituitary hormone deficiency v0.225 NLGN3 Chirag Patel Classified gene: NLGN3 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.225 NLGN3 Chirag Patel Gene: nlgn3 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.224 Chirag Patel Copied gene NLGN3 from panel Mendeliome
Pituitary hormone deficiency v0.224 NLGN3 Chirag Patel gene: NLGN3 was added
gene: NLGN3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NLGN3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NLGN3 were set to 28584888; 12669065; 25167861
Phenotypes for gene: NLGN3 were set to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Hypogonadotropic hypogonadism v0.133 Chirag Patel Copied gene NLGN3 from panel Mendeliome
Hypogonadotropic hypogonadism v0.133 NLGN3 Chirag Patel gene: NLGN3 was added
gene: NLGN3 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NLGN3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NLGN3 were set to 28584888; 12669065; 25167861
Phenotypes for gene: NLGN3 were set to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel Marked gene: NEUROG3 as ready
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.223 Chirag Patel Copied gene NEUROG3 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.223 NEUROG3 Chirag Patel gene: NEUROG3 was added
gene: NEUROG3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NEUROG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG3 were set to 36149814; 27533310
Phenotypes for gene: NEUROG3 were set to Congenital malabsorptive diarrhea 4, MONDO:0012479; Hypogonadotropic hypogonadism, MONDO:0018555
Hypogonadotropic hypogonadism v0.132 NEUROG3 Chirag Patel Classified gene: NEUROG3 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.132 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel Marked gene: NEUROG3 as ready
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel Gene: neurog3 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.131 NEUROG3 Chirag Patel gene: NEUROG3 was added
gene: NEUROG3 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NEUROG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG3 were set to 36149814; 27533310
Phenotypes for gene: NEUROG3 were set to Congenital malabsorptive diarrhea 4, MONDO:0012479; Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: NEUROG3 was set to GREEN
Added comment: PMID 27533310 reports 4 individuals from 3 families with 2 different homozygous rare missense variants (p.L135P and p.R107S) in NEUROG3 presenting with hypogonadotropic hypogonadism, congenital malabsorptive diarrhea, neonatal diabetes and short stature. No functional studies.

PMID 36149814 describes 3 unrelated Thai patients with families with 2 different homozygous rare missense variants ((p.Thr124Arg and p.Arg95Pro) in NEUROG3 presenting with multiple pituitary hormone deficiencies (GH deficiency and hypogonadotropic hypogonadism). Luciferase reporter assay showing markedly reduced transcriptional activity for both variants and western blot confirmed protein expression, indicating loss‑of‑function.
Sources: Literature
Motor Neurone Disease v1.49 ERBB4 Zornitza Stark Classified gene: ERBB4 as Green List (high evidence)
Motor Neurone Disease v1.49 ERBB4 Zornitza Stark Gene: erbb4 has been classified as Green List (High Evidence).
Mendeliome v1.4767 ERBB4 Zornitza Stark Classified gene: ERBB4 as Green List (high evidence)
Mendeliome v1.4767 ERBB4 Zornitza Stark Gene: erbb4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Marked gene: LEPR as ready
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Gene: lepr has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.130 LEPR Chirag Patel Phenotypes for gene: LEPR were changed from Obesity, morbid, due to leptin receptor deficiency (MIM#614963) to Obesity due to leptin receptor gene deficiency, MONDO:0013992
Hypogonadotropic hypogonadism v0.129 LEPR Chirag Patel Publications for gene: LEPR were set to 17229951; 29545012
Hypogonadotropic hypogonadism v0.128 Chirag Patel Added reviews for gene LEPR from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.222 LEPR Chirag Patel Phenotypes for gene: LEPR were changed from Obesity, morbid, due to leptin receptor deficiency (MIM#614963) to Obesity due to leptin receptor gene deficiency, MONDO:0013992
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Marked gene: LEPR as ready
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Gene: lepr has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.221 LEPR Chirag Patel Publications for gene: LEPR were set to 17229951; 29545012
Pituitary hormone deficiency v0.220 LEPR Chirag Patel reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31658438; Phenotypes: Obesity due to leptin receptor gene deficiency, MONDO:0013992; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.220 Chirag Patel Copied gene LEPR from panel Mendeliome
Pituitary hormone deficiency v0.220 LEPR Chirag Patel gene: LEPR was added
gene: LEPR was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable, clinical trial tags were added to gene: LEPR.
Mode of inheritance for gene: LEPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEPR were set to 17229951; 29545012
Phenotypes for gene: LEPR were set to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Hypogonadotropic hypogonadism v0.127 Chirag Patel Copied gene LEPR from panel Mendeliome
Hypogonadotropic hypogonadism v0.127 LEPR Chirag Patel gene: LEPR was added
gene: LEPR was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable, clinical trial tags were added to gene: LEPR.
Mode of inheritance for gene: LEPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEPR were set to 17229951; 29545012
Phenotypes for gene: LEPR were set to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Marked gene: TBX3 as ready
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Gene: tbx3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.219 TBX3 Chirag Patel Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Pituitary hormone deficiency v0.218 Chirag Patel Added reviews for gene TBX3 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Marked gene: TBX3 as ready
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Gene: tbx3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.126 TBX3 Chirag Patel Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Hypogonadotropic hypogonadism v0.125 TBX3 Chirag Patel reviewed gene: TBX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40485890, 39788453, 36937985, 30550377; Phenotypes: Ulnar-mammary syndrome, MONDO:0008411; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.217 Chirag Patel Copied gene TBX3 from panel Radial Ray Abnormalities
Pituitary hormone deficiency v0.217 TBX3 Chirag Patel gene: TBX3 was added
gene: TBX3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Phenotypes for gene: TBX3 were set to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Hypogonadotropic hypogonadism v0.125 Chirag Patel Copied gene TBX3 from panel Radial Ray Abnormalities
Hypogonadotropic hypogonadism v0.125 TBX3 Chirag Patel gene: TBX3 was added
gene: TBX3 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX3 were set to 9207801; 19938096; 28145909
Phenotypes for gene: TBX3 were set to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.207 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Phenotypes for gene: TUBB3 were changed from to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Publications for gene: TUBB3 were set to
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.206 TUBB3 Chirag Patel Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.205 Chirag Patel Added reviews for gene TUBB3 from panel Tubulinopathies
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.216 Chirag Patel Copied gene TUBB3 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.216 TUBB3 Chirag Patel gene: TUBB3 was added
gene: TUBB3 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB3 were set to 34652576; 25559402
Phenotypes for gene: TUBB3 were set to TUBB3-related tubulinopathy, MONDO:0100154
Hypogonadotropic hypogonadism v0.124 TUBB3 Chirag Patel Classified gene: TUBB3 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.124 TUBB3 Chirag Patel Gene: tubb3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel Marked gene: TUBB3 as ready
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel Gene: tubb3 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.123 TUBB3 Chirag Patel gene: TUBB3 was added
gene: TUBB3 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB3 were set to 34652576; 25559402
Phenotypes for gene: TUBB3 were set to TUBB3-related tubulinopathy, MONDO:0100154
Review for gene: TUBB3 was set to GREEN
Added comment: PMID 34652576 reports 14 individuals from 13 unrelated families with the same heterozygous de novo TUBB3 rare missense variant (p.Arg262His) presenting with congenital fibrosis of the extraocular muscles (CFEOM3), facial weakness, distal contractures, early‑onset peripheral neuropathy, and Kallmann syndrome (hypogonadotropic hypogonadism with anosmia). Detailed phenotyping and functional assays show dominant altered‑function of the mutant tubulin.

PMID 25559402 reports 4 affected individuals from 1 family (mother and 3 sons) with heterozygous TUBB3 rare missense variant (p.E410K) showing CFEOM, facial weakness, developmental delay, and variable endocrine abnormalities including hypogonadotropic hypogonadism, growth‑hormone deficiency and possible hypothyroidism. No functional data.
Sources: Literature
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel Marked gene: POU6F2 as ready
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4766 POU6F2 Chirag Patel Publications for gene: POU6F2 were set to
Mendeliome v1.4765 POU6F2 Chirag Patel Phenotypes for gene: POU6F2 were changed from to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4764 POU6F2 Chirag Patel Mode of inheritance for gene: POU6F2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4763 POU6F2 Chirag Patel Classified gene: POU6F2 as Amber List (moderate evidence)
Mendeliome v1.4763 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.215 Chirag Patel Copied gene POU6F2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.215 POU6F2 Chirag Patel gene: POU6F2 was added
gene: POU6F2 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: POU6F2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POU6F2 were set to 37600690
Phenotypes for gene: POU6F2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4762 Chirag Patel Added reviews for gene POU6F2 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Marked gene: POU6F2 as ready
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Classified gene: POU6F2 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.122 POU6F2 Chirag Patel Gene: pou6f2 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.121 POU6F2 Chirag Patel gene: POU6F2 was added
gene: POU6F2 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: POU6F2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POU6F2 were set to 37600690
Phenotypes for gene: POU6F2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: POU6F2 was set to AMBER
Added comment: PMID 37600690 reports 15 individuals from 12 unrelated families with idiopathic hypogonadotropic hypogonadism (IHH). Twelve rare missense variants in functional POU domains were identified. Inheritance includes autosomal recessive (Family‑A homozygous, p.Gly601Arg variant), autosomal dominant with variable penetrance, and a de novo case (Family‑I). All variants were classified as VUS. Functional assays in a human GnRH cell line showed the p.Gly601Arg variant abolished repression of GNRH1, supporting loss‑of‑function as the disease mechanism. The p.Asn629His variant (2 families) was common the Turkish population and had no effect on functional assays.
Sources: Literature
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel Marked gene: RNF216 as ready
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel Gene: rnf216 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel Marked gene: RNF216 as ready
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel Gene: rnf216 has been classified as Green List (High Evidence).
Mendeliome v1.4761 RNF216 Chirag Patel Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism MIM#212840 to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Mendeliome v1.4760 RNF216 Chirag Patel Publications for gene: RNF216 were set to 23656588
Pituitary hormone deficiency v0.214 Chirag Patel Copied gene RNF216 from panel Differences of Sex Development
Pituitary hormone deficiency v0.214 RNF216 Chirag Patel gene: RNF216 was added
gene: RNF216 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Phenotypes for gene: RNF216 were set to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Mendeliome v1.4759 Chirag Patel Added reviews for gene RNF216 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.120 Chirag Patel Copied gene RNF216 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.120 RNF216 Chirag Patel gene: RNF216 was added
gene: RNF216 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Phenotypes for gene: RNF216 were set to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Differences of Sex Development v1.52 RNF216 Chirag Patel Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism, MIM# 212840 to Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935
Differences of Sex Development v1.51 RNF216 Chirag Patel Publications for gene: RNF216 were set to 25841028; 23656588; 38050071
Differences of Sex Development v1.51 RNF216 Chirag Patel Publications for gene: RNF216 were set to 25841028; 23656588
Differences of Sex Development v1.50 RNF216 Chirag Patel reviewed gene: RNF216: Rating: GREEN; Mode of pathogenicity: None; Publications: 38050071; Phenotypes: Cerebellar ataxia-hypogonadism syndrome, MONDO:0008935; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4758 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Mendeliome v1.4758 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.213 Chirag Patel Copied gene PLXNB1 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.213 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4758 Chirag Patel Copied gene PLXNB1 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4758 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Marked gene: PLXNB1 as ready
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Classified gene: PLXNB1 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.119 PLXNB1 Chirag Patel Gene: plxnb1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.118 PLXNB1 Chirag Patel gene: PLXNB1 was added
gene: PLXNB1 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: PLXNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNB1 were set to 35170806
Phenotypes for gene: PLXNB1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Review for gene: PLXNB1 was set to AMBER
Added comment: 6 individuals from 6 unrelated families with 6 different heterozygous missense PLXNB1 variants presenting with normosmic idiopathic hypogonadotropic hypogonadism (delayed puberty, low LH/FSH, normal olfaction). All variants were rare but classified as VUS (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, p.C1318R). 3 variants were inherited from an unaffected parent, but parental status could not be clarified for 3 variants could not be clarified. Functional assay of p.R1031H variant showed reduced membrane expression and impaired GnRH‑cell migration, supporting a dominant‑negative mechanism.
Sources: Literature
Pituitary hormone deficiency v0.212 SMCHD1 Chirag Patel Publications for gene: SMCHD1 were set to 28067909
Pituitary hormone deficiency v0.211 SMCHD1 Chirag Patel Marked gene: SMCHD1 as ready
Pituitary hormone deficiency v0.211 SMCHD1 Chirag Patel Gene: smchd1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.211 Chirag Patel Added reviews for gene SMCHD1 from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Marked gene: SMCHD1 as ready
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Gene: smchd1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.117 SMCHD1 Chirag Patel Publications for gene: SMCHD1 were set to 28067909
Hypogonadotropic hypogonadism v0.116 SMCHD1 Chirag Patel reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28067909, 38808953; Phenotypes: Arhinia, choanal atresia, microphthalmia MONDO:0011323; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.210 Chirag Patel Copied gene SMCHD1 from panel Choanal atresia
Pituitary hormone deficiency v0.210 SMCHD1 Chirag Patel gene: SMCHD1 was added
gene: SMCHD1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMCHD1 were set to 28067909
Phenotypes for gene: SMCHD1 were set to Bosma arhinia microphthalmia syndrome, MIM# 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323
Mode of pathogenicity for gene: SMCHD1 was set to Other
Hypogonadotropic hypogonadism v0.116 Chirag Patel Copied gene SMCHD1 from panel Choanal atresia
Hypogonadotropic hypogonadism v0.116 SMCHD1 Chirag Patel gene: SMCHD1 was added
gene: SMCHD1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMCHD1 were set to 28067909
Phenotypes for gene: SMCHD1 were set to Bosma arhinia microphthalmia syndrome, MIM# 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323
Mode of pathogenicity for gene: SMCHD1 was set to Other
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel Marked gene: DLG2 as ready
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel Gene: dlg2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.209 Chirag Patel Copied gene DLG2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.209 DLG2 Chirag Patel gene: DLG2 was added
gene: DLG2 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: DLG2.
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to 32341572
Phenotypes for gene: DLG2 were set to delayed puberty, self-limited, MONDO:0859205
Hypertrophic cardiomyopathy v1.25 POPDC2 Achchuthan Shanmugasundram reviewed gene: POPDC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41456958; Phenotypes: Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.431 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Skeletal dysplasia v0.431 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Skeletal dysplasia. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Radial Ray Abnormalities v1.22 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Radial Ray Abnormalities v1.22 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Radial Ray Abnormalities. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Growth failure v1.103 Sarah Milton Copied Region SHOX downstream regulatory region from panel Mendeliome
Growth failure v1.103 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Growth failure. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Mendeliome v1.4757 SHOX downstream regulatory region Sarah Milton Region: SHOX downstream regulatory region was added
Region: SHOX downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: SHOX downstream regulatory region.
Mode of inheritance for Region: SHOX downstream regulatory region was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for Region: SHOX downstream regulatory region were set to PMID: 30250174; 22791839; 23636926; 20301394
Phenotypes for Region: SHOX downstream regulatory region were set to Leri-Weill dyschondrosteosis (MIM#127300); Short stature, idiopathic familial (MIM#300582)
Penetrance for Region: SHOX downstream regulatory region were set to Incomplete
Review for Region: SHOX downstream regulatory region was set to GREEN
Added comment: Deletions downstream of the SHOX coding region are known to be associated with idiopathic short stature and Leri-Weill dyschondrosteosis.

These deletions affect a conserved non coding element.
A recurrent 47.5kb deletion has been identified in a number of individuals with highly variable severity ranging from unaffected to Madelung deformity, short stature and mesomelia.

Supportive luciferase reporter assays in animal models confirm limb enhancer activity of this region.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.148 SPATA16 Zornitza Stark Publications for gene: SPATA16 were set to 17847006; 27086357; 29065458
Infertility and Recurrent Pregnancy Loss v1.147 SPATA16 Zornitza Stark Classified gene: SPATA16 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.147 SPATA16 Zornitza Stark Gene: spata16 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.146 SPATA16 Zornitza Stark reviewed gene: SPATA16: Rating: GREEN; Mode of pathogenicity: None; Publications: 30912172, 33877510, 39045326, 40376536; Phenotypes: Spermatogenic failure 6 MIM#102530, Spermatogenic failure 6 MONDO:0007060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4756 SPATA16 Zornitza Stark Publications for gene: SPATA16 were set to 17847006; 27086357; 29065458
Mendeliome v1.4755 SPATA16 Zornitza Stark Classified gene: SPATA16 as Green List (high evidence)
Mendeliome v1.4755 SPATA16 Zornitza Stark Gene: spata16 has been classified as Green List (High Evidence).
Mendeliome v1.4754 SPATA16 Zornitza Stark reviewed gene: SPATA16: Rating: GREEN; Mode of pathogenicity: None; Publications: 40376536, 39045326, 33877510, 30912172; Phenotypes: spermatogenic failure 6, MONDO:0007060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4754 MT-TQ Rylee Peters reviewed gene: MT-TQ: Rating: AMBER; Mode of pathogenicity: None; Publications: 38730005, 32588991; Phenotypes: Mitochondrial disease (MONDO:0044970), MT-TQ-related; Mode of inheritance: MITOCHONDRIAL
Fetal anomalies v1.559 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 39994693
Phenotypes for gene: PAK2 were set to ?Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to AMBER
Added comment: Domenach (2025): bilateral pleural effusion/chylothorax in a fetus at 24 weeks. Lit review notes an additional 2/5 probands with pleural effusion (1 also having chylothorax)
Sources: Literature
Congenital Heart Defect v0.535 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 38894571
Phenotypes for gene: PAK2 were set to ?Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to GREEN
Added comment: Additional patients in Schnur 2024 have some CHD, including PDA, ASD, VSD
Sources: Literature
Syndromic Retinopathy v0.257 PAK2 Elena Savva gene: PAK2 was added
gene: PAK2 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAK2 were set to PMID: 38894571
Phenotypes for gene: PAK2 were set to Knobloch syndrome 2 MIM#618458
Review for gene: PAK2 was set to GREEN
Added comment: Additional patients in Schnur 2024 have retinal detachment/retinopathy, described in 4/4 probands with de novo missense, one of which had an additional inherited chromosomal abnormality.
Sources: Literature
Genetic Epilepsy v1.409 PAK2 Elena Savva reviewed gene: PAK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40247748; Phenotypes: ?Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4754 PLEKHM2 Rylee Peters reviewed gene: PLEKHM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 40054934; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, PLEKHM2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4754 NSMCE3 Rylee Peters reviewed gene: NSMCE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40728043, 33741030, 27427983; Phenotypes: Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.39 ALPL Lilian Downie Marked gene: ALPL as ready
Genomic newborn screening: ICoNS v0.39 ALPL Lilian Downie Gene: alpl has been classified as Red List (Low Evidence).
Genomic newborn screening: ICoNS v0.39 ALPL José Manuel González de Aledo Castillo reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genomic newborn screening: ICoNS v0.39 CD3D Lilian Downie gene: CD3D was added
gene: CD3D was added to Genomic newborn screening: ICoNS. Sources: Expert List
Mode of inheritance for gene: CD3D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD3D were set to PMID: 38022338, 36944331, 15729559, 16672702, https://doi.org/10.1016/j.jaci.2022.10.022
Phenotypes for gene: CD3D were set to primary immunodeficiency; life-threatening infections: recurrent bacterial/viral/ fungal infections; chronic diarrhoea; recurrent respiratory infections; failure to thrive. Immunologic profile shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype.; OMIM: 186790
Added comment: Gene is in Baby Detect (Liege, Belgium) gene panel
Sources: Expert List
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Marked gene: RPS26 as ready
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Gene: rps26 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Classified gene: RPS26 as Green List (high evidence)
Genomic newborn screening: ICoNS v0.38 RPS26 Lilian Downie Gene: rps26 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Marked gene: RPS19 as ready
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Gene: rps19 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Classified gene: RPS19 as Green List (high evidence)
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Added comment: Comment on list classification: Some challenges identifying variants; deep intronic, large deletions reported
Genomic newborn screening: ICoNS v0.37 RPS19 Lilian Downie Gene: rps19 has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.36 RPS19 Jorune Balciuniene changed review comment from: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation; to: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant.

Genetic testing complexities: Deep intronic pathogenic variant c.172+350C>T

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Genomic newborn screening: ICoNS v0.36 ALPL Lilian Downie gene: ALPL was added
gene: ALPL was added to Genomic newborn screening: ICoNS. Sources: Expert List
Mode of inheritance for gene: ALPL was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: ClinGen
ALPL is curated by the ClinGen Skeletal Disorders Gene Curation Expert Panel and has Definitive gene–disease validity for both ALPL-related autosomal recessive hypophosphatasia and ALPL-related autosomal dominant hypophosphatasia.
Treatment
Enzyme replacement therapy (ERT) for avoiding/reducing respiratory failure leading to long-term ventilatory support or death and for rickets or fractures, and also avoidance of bisphosphonates as a management consideration.
Asfotase alfa (ERT) improves pulmonary function, bone health and calcium homeostasis, and survival in infantile and early childhood hypophosphatasia.
Asfotase alfa improved survival in perinatal/infantile hypophosphatasia versus historical controls, with survival reported as 95% vs 42% at age 1 year and 84% vs 27% at age 5 years. Also marked benefit among treated patients needing respiratory support has been reported.
Genomic newborn screening challenges
The main genomic-screening challenge is the extreme phenotype spectrum: ALPL can cause perinatal lethal, infantile, childhood, adult, and odontohypophosphatasia presentations, and both AR and AD inheritance occur. Dominant-negative effects have been described in some autosomal dominant cases.
Another major issue is reduced penetrance/variable expressivity, especially for heterozygous ALPL variants. Penetrance in adult heterozygotes is low or incompletely understood
Variants of interest
The ALPL field has created a dedicated international variant-classification project and database
https://alplmutationdatabase.jku.at/
At the gene level, ALPL has more than 440 reported variants, including missense, nonsense, splice-site, small deletion/insertion, and other disruptive variants. Missense variants are common. Rather than a small number of recurrent variants, ALPL is characterized by broad allelic heterogeneity, with both loss-of-function and dominant-negative missense variants contributing to disease.
Genomic newborn screening inclusion
Included in most genomic newborn screening programs, but some of them just the recessive form
Traditional newborn screening
Hypophosphatasia is not part of standard routine traditional newborn screening panels. There is a pilot biochemical newborn screening study from Kumamoto Prefecture, Japan, which the authors describe as the first study on newborn screening for HPP worldwide. It used dried blood spots to measure TNAP (tissue-nonspecific alkaline phosphatase) activity in 45,632 newborns and identified one child who later showed HPP-related manifestations.
Sources: Expert List
Craniosynostosis v1.85 ARSB Judit Garcia reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 17458871, 30118150, 34948256; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genomic newborn screening: ICoNS v0.35 RPS26 Jorune Balciuniene gene: RPS26 was added
gene: RPS26 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPS26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS26 were set to 20301769, 30503522
Phenotypes for gene: RPS26 were set to Diamond-Blackfan anemia 10
Penetrance for gene: RPS26 were set to unknown
Review for gene: RPS26 was set to GREEN
Added comment: Accounts for 6-9% of all DBA.
Penetrance high, variable expressivity

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Genomic newborn screening: ICoNS v0.35 RPS24 Jorune Balciuniene gene: RPS24 was added
gene: RPS24 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPS24 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS24 were set to 39568018, 17186470, 25946618
Phenotypes for gene: RPS24 were set to Diamond-blackfan anemia 3
Penetrance for gene: RPS24 were set to unknown
Review for gene: RPS24 was set to GREEN
Added comment: Accounts for 2-3% of all DBA.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Genomic newborn screening: ICoNS v0.35 RPS17 Jorune Balciuniene gene: RPS17 was added
gene: RPS17 was added to Genomic newborn screening: ICoNS. Sources: ClinGen,Literature
Mode of inheritance for gene: RPS17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS17 were set to 20301769
Phenotypes for gene: RPS17 were set to Diamond-Blackfan anemia 4
Penetrance for gene: RPS17 were set to unknown
Review for gene: RPS17 was set to GREEN
gene: RPS17 was marked as current diagnostic
Added comment: Accounts for 1-3% of all DBA.
Penetrance seems high, variable expressivity.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: ClinGen, Literature
Genomic newborn screening: ICoNS v0.35 RPL5 Jorune Balciuniene gene: RPL5 was added
gene: RPL5 was added to Genomic newborn screening: ICoNS. Sources: ClinGen,Literature
Mode of inheritance for gene: RPL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL5 were set to 19773262
Phenotypes for gene: RPL5 were set to Diamond-Blackfan anemia 6
Penetrance for gene: RPL5 were set to Incomplete
Review for gene: RPL5 was set to GREEN
gene: RPL5 was marked as current diagnostic
Added comment: Accounts for 7-12% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Manifestation often include small gestational age, craniofacial, congenital heart, and thumb defects.

More than 90% of DBA patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: ClinGen, Literature
Genomic newborn screening: ICoNS v0.35 RPS19 Jorune Balciuniene edited their review of gene: RPS19: Added comment: Accounts for 25-30% of all DBA.
Penetrance seems to be high but incomplete with variable expressivity. Missense variants are less penetrant

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation; Set current diagnostic: yes
Genomic newborn screening: ICoNS v0.35 RPL11 Jorune Balciuniene gene: RPL11 was added
gene: RPL11 was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: RPL11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL11 were set to 19773262, 20301769
Phenotypes for gene: RPL11 were set to Diamond-Blackfan anemia 7
Penetrance for gene: RPL11 were set to Incomplete
Review for gene: RPL11 was set to GREEN
gene: RPL11 was marked as current diagnostic
Added comment: Accounts for 5%-7% of all DBA.
Pathogenic variants in RPL11 are predominantly associated with thumb abnormalities. Penetrance seems to be high but incomplete (a couple of families with asymptomatic parents reported) with variable expressivity

More than 90% of the patients present during the first year of life. The diagnosis is generally made at 3 months, of age with a range from birth to adulthood.

Treatment: Corticosteroids and red blood cell transfusions are the mainstays of therapy. Curative treatment - hematopoietic stem cell transplantation
Sources: Literature
Severe Combined Immunodeficiency v1.30 CD3D Kristina Hovhannesyan reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38022338, 36944331, 15729559, 16672702, https://doi.org/10.1016/j.jaci.2022.10.022; Phenotypes: primary immunodeficiency, life-threatening infections: recurrent bacterial/viral/ fungal infections, chronic diarrhoea, recurrent respiratory infections, failure to thrive. Immunologic profile shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype., OMIM: 186790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.32 MRAP2 Zornitza Stark Publications for gene: MRAP2 were set to 23869016; 31700171; 27474872; 26795956
Severe early-onset obesity v1.31 MRAP2 Zornitza Stark Classified gene: MRAP2 as Green List (high evidence)
Severe early-onset obesity v1.31 MRAP2 Zornitza Stark Gene: mrap2 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.30 MRAP2 Zornitza Stark edited their review of gene: MRAP2: Added comment: Multiple studies PMIDs 31700171, 27474872, 37888144, 40822950, 29704154, 39574659a report 31 individuals from 13 unrelated families carrying heterozygous loss‑of‑function MRAP2 variants that cause early‑onset severe obesity, hyperphagia, hypertension and hyperglycaemia. Functional assays in CHO and HEK293 cells demonstrate reduced MC4R/MC3R‑dependent cAMP signaling, supporting a loss‑of‑function mechanism.; Changed rating: GREEN; Changed publications: 40822950, 39574659, 37888144, 33026327, 31700171, 29704154, 27474872
Mendeliome v1.4754 MRAP2 Zornitza Stark Publications for gene: MRAP2 were set to 23869016; 31700171; 27474872; 26795956
Mendeliome v1.4753 MRAP2 Zornitza Stark Classified gene: MRAP2 as Green List (high evidence)
Mendeliome v1.4753 MRAP2 Zornitza Stark Gene: mrap2 has been classified as Green List (High Evidence).
Mendeliome v1.4752 MRAP2 Zornitza Stark edited their review of gene: MRAP2: Added comment: Multiple studies PMIDs 31700171, 27474872, 37888144, 40822950, 29704154, 39574659a report 31 individuals from 13 unrelated families carrying heterozygous loss‑of‑function MRAP2 variants that cause early‑onset severe obesity, hyperphagia, hypertension and hyperglycaemia. Functional assays in CHO and HEK293 cells demonstrate reduced MC4R/MC3R‑dependent cAMP signaling, supporting a loss‑of‑function mechanism.; Changed rating: GREEN; Changed publications: 40822950, 39574659, 37888144, 33026327, 31700171, 29704154, 27474872; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Marked gene: MOV10L1 as ready
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.146 MOV10L1 Zornitza Stark Publications for gene: MOV10L1 were set to 35476666; 20534472
Infertility and Recurrent Pregnancy Loss v1.145 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.145 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.144 MOV10L1 Zornitza Stark edited their review of gene: MOV10L1: Added comment: PMIDs 35413094 and 39122675 report five individuals from five unrelated families with biallelic MOV10L1 variants presenting with non‑obstructive azoospermia due to spermatogenic failure (maturation arrest). Immunohistochemistry, minigene splicing assays, and piRNA‑seq demonstrate loss of MOV10L1 expression and disrupted piRNA biogenesis, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 35476666, 20534472, 39122675
Mendeliome v1.4752 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Green List (high evidence)
Mendeliome v1.4752 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Green List (High Evidence).
Mendeliome v1.4751 MOV10L1 Zornitza Stark edited their review of gene: MOV10L1: Added comment: PMIDs 35413094 and 39122675 report five individuals from five unrelated families with biallelic MOV10L1 variants presenting with non‑obstructive azoospermia due to spermatogenic failure (maturation arrest). Immunohistochemistry, minigene splicing assays, and piRNA‑seq demonstrate loss of MOV10L1 expression and disrupted piRNA biogenesis, supporting pathogenicity.; Changed rating: GREEN; Changed publications: 39122675, 35413094; Changed phenotypes: Infertility disorder, MONDO:0005047, MOV10L1-related
Infertility and Recurrent Pregnancy Loss v1.144 Zornitza Stark Copied gene MOV10L1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.144 MOV10L1 Zornitza Stark gene: MOV10L1 was added
gene: MOV10L1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: MOV10L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOV10L1 were set to 35476666; 20534472
Phenotypes for gene: MOV10L1 were set to Spermatogenic failure 73, MIM#619878
Intellectual disability syndromic and non-syndromic v1.753 NPRL2 Lucy Spencer Classified gene: NPRL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.753 NPRL2 Lucy Spencer Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.752 NPRL2 Lucy Spencer gene: NPRL2 was added
gene: NPRL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NPRL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL2 were set to 26505888; 34376795; 40804712; 30093711
Phenotypes for gene: NPRL2 were set to epilepsy, familial focal, with variable foci 2 (MIM#617116)
Review for gene: NPRL2 was set to AMBER
Added comment: Intellectual disability/developmental delay has been reported in some individuals with NPRL2-related epilepsy;

PMID: 30093711 3 patients with NPRL2 variants and 2 have ID, 2 also have brain abnormalities. NPRL2 forms the GATOR1 complex with DEPDC5 and NPLR3, the paper describes the phenotype of all 3 as overlapping- ID better reported in the other genes

PMID: 40804712 1 individual with mild ID and severe speech impairment. has a frameshift variant in NPRL2

PMID: 34376795 proband with seizures and dev delay/DEE, mother had ID and seizures. both had a canonical splice in NPRL2

PMID: 26505888 1 proband with ID and temporal lobe epilepsy. Had a maternally inherited missense Thr110Ser only 1 het i gnomad

Borderline amber/green for this panel
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.751 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Intellectual disability syndromic and non-syndromic v1.750 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Genetic Epilepsy v1.409 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Genetic Epilepsy v1.408 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Mendeliome v1.4751 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Mendeliome v1.4750 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Autism v0.249 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Autism v0.248 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Angelman Rett like syndromes v1.15 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1, MIM# 309530; Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Angelman Rett like syndromes v1.14 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed phenotypes: Intellectual developmental disorder, X-linked 1, MIM# 309530, Neurodevelopmental disorder, X-linked, with poor or absent speech and behavioral abnormalities, MIM# 301164
Intellectual disability syndromic and non-syndromic v1.750 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Neurodevelopmental disorder (MONDO#0700092), PSMC5-related to Yu-Kury neurodevelopmental syndrome, MIM# 621565
Intellectual disability syndromic and non-syndromic v1.749 PSMC5 Zornitza Stark edited their review of gene: PSMC5: Changed rating: GREEN; Changed phenotypes: Yu-Kury neurodevelopmental syndrome, MIM# 621565
Mendeliome v1.4750 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Neurodevelopmental disorder (MONDO#0700092), PSMC5-related to Yu-Kury neurodevelopmental syndrome, MIM# 621565
Mendeliome v1.4749 PSMC5 Zornitza Stark reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Yu-Kury neurodevelopmental syndrome, MIM# 621565; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4749 SLIT2 Lucy Spencer changed review comment from: PMID: 26026792 reported A98T (5 hets in gnomad), S566N (111 hets in gnomad) and K904N (1 het in gnomad).

PMID: 34059960 reports another three proband with CAKUT and variants in SLIT2. D1276N (absent from gnomad), R287H (2 hets in gnomad), T757A (absent from gnomad).

6 individuals total however 1 variant is common in gnomad and another has 5 hets. No compelling functional data on the variants. The only variant with inheritance ifnromation was inherited from an unaffected parent but that was the common S566N variant.

Borderline amber/green; to: PMID: 26026792 reported A98T (5 hets in gnomad), S566N (111 hets in gnomad) and K904N (1 het in gnomad).

PMID: 34059960 reports another three proband with CAKUT and variants in SLIT2. D1276N (absent from gnomad), R287H (2 hets in gnomad), T757A (absent from gnomad).

6 individuals total however 1 variant is common in gnomad and another has 5 hets. No compelling functional data on the variants but there is a KO mouse model recapitulating the phenotype. The only variant with inheritance ifnromation was inherited from an unaffected parent but that was the common S566N variant.

Borderline amber/green
Mendeliome v1.4749 SLIT2 Lucy Spencer Phenotypes for gene: SLIT2 were changed from CAKUT MONDO:0019719, SLIT2-related to Congenital anomaly of kidney and urinary tract MONDO:0019719, SLIT2-related
Mendeliome v1.4748 SLIT2 Lucy Spencer Publications for gene: SLIT2 were set to 26026792; 15130495
Mendeliome v1.4747 SLIT2 Lucy Spencer reviewed gene: SLIT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26026792, 34059960; Phenotypes: Congenital anomaly of kidney and urinary tract MONDO:0019719, SLIT2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4747 SPRY4 Lucy Spencer changed review comment from: PMID: 31200363 identified Ser259Phe (p.236 in gnomad, only 1 het) in an individual with HH. They also had a variant in IGSF10 but it was common in gnomad. No functional data

PMID: 31781046 an individual with Kallman syndrome, identified Arg53Gln (p.30 in gnomad) which has over 80 hets and 2 homs in gnomad.

PMID: 32389901 in an individual with Kallman syndrome identified Thr68Ser (p.45 in gnomad) which only has 3 hets in gnomad. this individual also had a variant in PLXNA1 which is also amber for DSD due to high population frequencies of reported variants, and the variant in this case has 79 hets in gnomad.

PMID: 35316923 Only identified 2 common missense variants in patients with HH p.Lys177Arg and p.Ser241Tyr

So another 2 rare missense variants reported but no functional data available remains amber; to: PMID: 31200363 identified Ser259Phe (p.236 in gnomad, only 1 het) in an individual with HH. They also had a variant in IGSF10 but it was common in gnomad. No functional data

PMID: 31781046 an individual with Kallman syndrome, identified Arg53Gln (p.30 in gnomad) which has over 80 hets and 2 homs in gnomad.

PMID: 32389901 in an individual with Kallman syndrome identified Thr68Ser (p.45 in gnomad) which only has 3 hets in gnomad. this individual also had a variant in PLXNA1 which is also amber for DSD due to high population frequencies of reported variants, and the variant in this case has 79 hets in gnomad.

PMID: 35316923 Only identified 2 common missense variants in patients with HH p.Lys177Arg and p.Ser241Tyr

So another 2 rare missense variants reported but no functional data available REMAINS AMBER
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Changed phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266, Neurodevelopmental disorder, MONDO:0700092, SPRY4-related
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Changed rating: AMBER
Mendeliome v1.4747 SPRY4 Lucy Spencer edited their review of gene: SPRY4: Added comment: PMID: 28539120 identified Cys170Ser de novo in a proband with a neurodevelopmental condition. This individual also had 2 variants in AP4E1 (green and biallelic on the ID panel) one of which was a canonical splice. RED for this association; Changed rating: RED; Changed publications: 28539120; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPRY4-related
Early-onset Parkinson disease v2.55 RAB32 Lucy Spencer Publications for gene: RAB32 were set to 38614108; 38858457
Early-onset Parkinson disease v2.54 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Early-onset Parkinson disease v2.54 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.53 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Early-onset Parkinson disease v2.53 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.52 Lucy Spencer Added reviews for gene RAB32 from panel Mendeliome
Mendeliome v1.4747 RAB32 Lucy Spencer Publications for gene: RAB32 were set to 38614108; 38858457
Mendeliome v1.4746 RAB32 Lucy Spencer Classified gene: RAB32 as Green List (high evidence)
Mendeliome v1.4746 RAB32 Lucy Spencer Gene: rab32 has been classified as Green List (High Evidence).
Mendeliome v1.4745 RAB32 Lucy Spencer reviewed gene: RAB32: Rating: GREEN; Mode of pathogenicity: None; Publications: 38858457, 38614108, 38293014, 40118982, 40568674, 41103171; Phenotypes: Parkinson disease 26, autosomal dominant, susceptibility to MIM#620923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4745 SPRY4 Lucy Spencer Publications for gene: SPRY4 were set to 23643382
Mendeliome v1.4744 SPRY4 Lucy Spencer reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31200363, 31781046, 32389901, 35316923; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4744 WDHD1 Achchuthan Shanmugasundram gene: WDHD1 was added
gene: WDHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDHD1 were set to 41962535
Phenotypes for gene: WDHD1 were set to microcephalic osteodysplastic primordial dwarfism, MONDO:0000060
Review for gene: WDHD1 was set to GREEN
Added comment: PMID:41962535 (2026) reported the identification of biallelic hypomorphic variants in WDHD1 gene in 17 patients from 14 families with microcephalic primordial dwarfism (MPD) and a broad spectrum of additional abnormalities including acute liver failure. There is also functional evidence available from patient-derived fibroblasts which supports the disease association.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.207 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.206 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from Alagille syndrome, MIM#118450 to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Phenotypes for gene: JAG1 were changed from to Alagille syndrome, MIM#118450
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.205 JAG1 Chirag Patel Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel Marked gene: JAG1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel Gene: jag1 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 JAG1 Chirag Patel reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alagille syndrome, MIM#118450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.408 RYR3 Karina Sandoval reviewed gene: RYR3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39840699, 39220738, 25262651, 29667327; Phenotypes: undetermined early-onset epileptic encephalopathy (MONDO:0018614); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.39 SPPL2A Lucy Spencer Phenotypes for gene: SPPL2A were changed from Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, mycobacteriosis MIM#619549
Defects of intrinsic and innate immunity v1.38 SPPL2A Lucy Spencer Publications for gene: SPPL2A were set to 30127434
Defects of intrinsic and innate immunity v1.37 SPPL2A Lucy Spencer Classified gene: SPPL2A as Green List (high evidence)
Defects of intrinsic and innate immunity v1.37 SPPL2A Lucy Spencer Gene: sppl2a has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.37 Lucy Spencer Added reviews for gene SPPL2A from panel Mendeliome
Mendeliome v1.4744 SPPL2A Lucy Spencer Phenotypes for gene: SPPL2A were changed from Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, mycobacteriosis MIM#619549
Mendeliome v1.4743 SPPL2A Lucy Spencer Publications for gene: SPPL2A were set to 30127434
Mendeliome v1.4742 SPPL2A Lucy Spencer Classified gene: SPPL2A as Green List (high evidence)
Mendeliome v1.4742 SPPL2A Lucy Spencer Gene: sppl2a has been classified as Green List (High Evidence).
Mendeliome v1.4741 SPPL2A Lucy Spencer reviewed gene: SPPL2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30127434, 37931111, 39586751; Phenotypes: Immunodeficiency 86, mycobacteriosis MIM#619549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.69 CRX Chirag Patel Marked gene: CRX as ready
Cone-rod Dystrophy v0.69 CRX Chirag Patel Gene: crx has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.69 Chirag Patel Added reviews for gene CRX from panel Retinitis pigmentosa
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.414 SPATA22 Lucy Spencer Phenotypes for gene: SPATA22 were changed from Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143 to Spermatogenic failure 96, MIM#621001; Premature ovarian failure 25, MIM#621002
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.413 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to PMID: 35285020
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.412 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.412 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.143 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to 35285020
Infertility and Recurrent Pregnancy Loss v1.142 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.142 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Mendeliome v1.4741 SPATA22 Lucy Spencer Publications for gene: SPATA22 were set to 35285020
Mendeliome v1.4740 SPATA22 Lucy Spencer Classified gene: SPATA22 as Green List (high evidence)
Mendeliome v1.4740 SPATA22 Lucy Spencer Gene: spata22 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.411 Lucy Spencer Added reviews for gene SPATA22 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.141 Lucy Spencer Copied gene SPATA22 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.141 SPATA22 Lucy Spencer gene: SPATA22 was added
gene: SPATA22 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: SPATA22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA22 were set to 35285020
Phenotypes for gene: SPATA22 were set to Spermatogenic failure 96, MIM#621001; Premature ovarian failure 25, MIM#621002
Mendeliome v1.4739 SPATA22 Lucy Spencer reviewed gene: SPATA22: Rating: GREEN; Mode of pathogenicity: None; Publications: 34392356, 35413094, 35285020; Phenotypes: Spermatogenic failure 96, MIM#621001, Premature ovarian failure 25, MIM#621002; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pierre Robin Sequence v0.64 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Intellectual disability syndromic and non-syndromic v1.749 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Mendeliome v1.4739 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Differences of Sex Development v1.50 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Differences of Sex Development v1.50 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Differences of Sex Development v1.50 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; 46,XX or XY DSD, EMX2-related
Differences of Sex Development v1.49 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Differences of Sex Development v1.49 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Differences of Sex Development v1.48 EMX2 Krithika Murali Marked gene: EMX2 as ready
Differences of Sex Development v1.48 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.64 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Pierre Robin sequence, EMX2-related to Pierre-Robin sequence, EMX2-related
Pierre Robin Sequence v0.64 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Pierre Robin sequence, EMX2-related
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Marked gene: EMX2 as ready
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Classified gene: EMX2 as Red List (low evidence)
Pierre Robin Sequence v0.63 EMX2 Krithika Murali Gene: emx2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Marked gene: EMX2 as ready
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.115 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Schizencephaly, MIM# 269160Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; 46,XX or XY DSD, EMX2-related
Hypogonadotropic hypogonadism v0.114 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Hypogonadotropic hypogonadism v0.113 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Hypogonadotropic hypogonadism v0.113 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.749 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Intellectual disability syndromic and non-syndromic v1.748 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to complex neurodevelopmental disorder - MONDO:0100038, EMX2-related; Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; DSD, EMX2-related
Intellectual disability syndromic and non-syndromic v1.747 EMX2 Krithika Murali Classified gene: EMX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.747 EMX2 Krithika Murali Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4739 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; DSD, EMX2-related
Pierre Robin Sequence v0.62 Krithika Murali Copied gene EMX2 from panel Mendeliome
Pierre Robin Sequence v0.62 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Pierre Robin Sequence. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Mendeliome v1.4738 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Intellectual disability syndromic and non-syndromic v1.746 Krithika Murali Added reviews for gene EMX2 from panel Mendeliome
Mendeliome v1.4737 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Mendeliome v1.4737 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.112 Krithika Murali Copied gene EMX2 from panel Mendeliome
Hypogonadotropic hypogonadism v0.112 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Differences of Sex Development v1.48 Krithika Murali Copied gene EMX2 from panel Mendeliome
Differences of Sex Development v1.48 EMX2 Krithika Murali gene: EMX2 was added
gene: EMX2 was added to Differences of Sex Development. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: EMX2.
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Phenotypes for gene: EMX2 were set to Schizencephaly, MIM# 269160
Mendeliome v1.4736 EMX2 Krithika Murali reviewed gene: EMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41765865, 34829455, 33434492, 25577462; Phenotypes: Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related, 46,XX or XY DSD, EMX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.361 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006 to Deafness, autosomal recessive 36, MIM# 609006; Deafness, autosomal dominant 91, MIM# 621556
Deafness_IsolatedAndComplex v1.360 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.359 ESPN Zornitza Stark edited their review of gene: ESPN: Changed phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, autosomal dominant 91, MIM# 621556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4736 ESPN Zornitza Stark Phenotypes for gene: ESPN were changed from Deafness, autosomal recessive 36, MIM# 609006; Deafness, neurosensory, without vestibular involvement, autosomal dominant, MIM# 609006 to Deafness, autosomal recessive 36, MIM# 609006; Deafness, autosomal dominant 91, MIM# 621556
Mendeliome v1.4735 ESPN Zornitza Stark Mode of inheritance for gene: ESPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4734 ESPN Zornitza Stark edited their review of gene: ESPN: Changed phenotypes: Deafness, autosomal recessive 36, MIM# 609006, Deafness, autosomal dominant 91, MIM# 621556; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.68 UBAP1L Zornitza Stark Phenotypes for gene: UBAP1L were changed from Cone-rod dystrophy (MONDO:0015993), UBAP1L-related to Retinal dystrophy, Zeitz-Han type, MIM# 621558
Cone-rod Dystrophy v0.67 UBAP1L Zornitza Stark reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal dystrophy, Zeitz-Han type, MIM# 621558; Mode of inheritance: None
Mendeliome v1.4734 UBAP1L Zornitza Stark Phenotypes for gene: UBAP1L were changed from Cone-rod dystrophy (MONDO:0015993), UBAP1L-related to Retinal dystrophy, Zeitz-Han type, MIM# 621558
Mendeliome v1.4733 UBAP1L Zornitza Stark reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal dystrophy, Zeitz-Han type, MIM# 621558; Mode of inheritance: None
Neuromuscular Superpanel v4.429 Bryony Thompson Changed child panels to: Hereditary Neuropathy; Hereditary Spastic Paraplegia; Muscular dystrophy and myopathy_Paediatric; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Motor Neurone Disease; Rhabdomyolysis and Metabolic Myopathy; Gastrointestinal neuromuscular disease; Congenital Myasthenia; Arthrogryposis; Skeletal Muscle Channelopathies
Mendeliome v1.4733 FOXJ3 Rylee Peters changed review comment from: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects. Functional assays demonstrate loss‑of‑function, reduced PTEN, mTOR hyper‑activation and neuronal migration defects.
Sources: Literature; to: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects.

Sources: Literature
Fetal anomalies v1.558 RNU4-2 Ee Ming Wong changed review comment from: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature; to: PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature
Mendeliome v1.4733 FOXJ3 Rylee Peters gene: FOXJ3 was added
gene: FOXJ3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXJ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ3 were set to 41803108
Phenotypes for gene: FOXJ3 were set to Focal epilepsy, MONDO:0005384, FOXJ3-related
Review for gene: FOXJ3 was set to AMBER
Added comment: PMID: 41803108 reports 5 individuals from 3 unrelated families with heterozygous missense FOXJ3 variants and autosomal dominant focal epilepsy with or without focal cortical dysplasia. The missense variants, p.N351S, p.I621V and p.P253T have 10 hets, 11 hets and 8 hets in gnomAD v4, respectively. Foxj3 knockdown in mouse brains results in neuronal migration defects. Functional assays demonstrate loss‑of‑function, reduced PTEN, mTOR hyper‑activation and neuronal migration defects.
Sources: Literature
Fetal anomalies v1.558 RNU4-2 Ee Ming Wong gene: RNU4-2 was added
gene: RNU4-2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RNU4-2 were set to 38991538; 40297424; 39830270; 39423747
Phenotypes for gene: RNU4-2 were set to ReNU syndrome (MIM# 620851), AD
Mode of pathogenicity for gene: RNU4-2 was set to Other
Review for gene: RNU4-2 was set to GREEN
gene: RNU4-2 was marked as current diagnostic
Added comment: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature
Defects of intrinsic and innate immunity v1.36 Sangavi Sivagnanasundram Added reviews for gene IRF9 from panel Mendeliome
Atrial Fibrillation v1.8 Sangavi Sivagnanasundram Added reviews for gene KCNA5 from panel Mendeliome
Bleeding and Platelet Disorders v1.77 Sangavi Sivagnanasundram Added reviews for gene KLKB1 from panel Mendeliome
Mendeliome v1.4732 KCNJ3 Sangavi Sivagnanasundram Deleted their review
Mendeliome v1.4732 LMAN2L Sangavi Sivagnanasundram reviewed gene: LMAN2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 40221759, 37667433; Phenotypes: intellectual disability, autosomal recessive 52, MONDO:0014815; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4732 KLKB1 Sangavi Sivagnanasundram reviewed gene: KLKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38050365, 34847617, 33807613, 33176434, 33073460, 32202057, 31984307, 30430790; Phenotypes: inherited prekallikrein deficiency, MONDO:0012901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4732 KLF13 Sangavi Sivagnanasundram Added comment: Comment on publications: Publications weren't updated at the time of review - no new evidence has been reported.
Mendeliome v1.4732 KLF13 Sangavi Sivagnanasundram Publications for gene: KLF13 were set to
Mendeliome v1.4731 KCNJ3 Sangavi Sivagnanasundram reviewed gene: KCNJ3: Rating: AMBER; Mode of pathogenicity: None; Publications: 38597354, 37963718, 30764634; Phenotypes: Epilepsy MONDO:0005027, Hereditary spastic paraplegia MONDO:0019064, Bradycardia MONDO:0007263; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4731 KCNA5 Sangavi Sivagnanasundram reviewed gene: KCNA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 36917789, 27630060, 26129877, 34199176; Phenotypes: atrial fibrillation, familial, 7, MONDO:0012828, pulmonary arterial hypertension MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4731 HAND2 Sangavi Sivagnanasundram reviewed gene: HAND2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26676105, 26865696; Phenotypes: HAND2 related congenital heart defect MONDO:0800476; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4731 IRF9 Sangavi Sivagnanasundram reviewed gene: IRF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 30143481, 30826365; Phenotypes: immunodeficiency 65, susceptibility to viral infections, MONDO:0032848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 KREMEN1 Sangavi Sivagnanasundram reviewed gene: KREMEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28813618; Phenotypes: ectodermal dysplasia 13, hair/tooth type, MONDO:0044305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 LRRC23 Sangavi Sivagnanasundram reviewed gene: LRRC23: Rating: GREEN; Mode of pathogenicity: None; Publications: 39054792; Phenotypes: spermatogenic failure 92, MONDO:0970999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4731 EMG1 Sangavi Sivagnanasundram reviewed gene: EMG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27798105, 26676230, 25708872; Phenotypes: Bowen-Conradi syndrome, MONDO:0008879; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v1.16 NDUFA5 Natalie Tan gene: NDUFA5 was added
gene: NDUFA5 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: NDUFA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA5 were set to 41916321
Phenotypes for gene: NDUFA5 were set to Complex I deficiency
Penetrance for gene: NDUFA5 were set to Complete
Review for gene: NDUFA5 was set to GREEN
Added comment: PMID:41916321 reports 4 individuals from 3 unrelated families with biallelic variants in NDUFA5, associated with a multi-system mitochondriopathy characterised by a complex I deficiency that was functionally confirmed via transcriptomics, proteomics and respiratory chain enzymology.
Sources: Literature
Mendeliome v1.4731 POU3F4 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: POU3F4 upstream regulatory region.
Eye Anterior Segment Abnormalities v1.21 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Glaucoma congenital v1.12 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Mendeliome v1.4730 PITX2 upstream regulatory region Sarah Milton Tag SV/CNV was removed from Region: PITX2 upstream regulatory region.
Tag regulatory region was added to Region: PITX2 upstream regulatory region.
Hand and foot malformations v0.89 PITX1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: PITX1 upstream regulatory region.
Mendeliome v1.4729 PITX1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: PITX1 upstream regulatory region.
Leukodystrophy v0.394 Sarah Milton Copied Region LMNB1 upstream region from panel Mendeliome
Leukodystrophy v0.394 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Leukodystrophy. Sources: Literature
regulatory region tags were added to Region: LMNB1 upstream region.
Mode of inheritance for Region: LMNB1 upstream region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: LMNB1 upstream region were set to PMID: 30842973; 30697589; 25701871
Phenotypes for Region: LMNB1 upstream region were set to Adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215
Ataxia v1.203 Sarah Milton Copied Region LMNB1 upstream region from panel Mendeliome
Ataxia v1.203 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Ataxia. Sources: Literature
regulatory region tags were added to Region: LMNB1 upstream region.
Mode of inheritance for Region: LMNB1 upstream region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: LMNB1 upstream region were set to PMID: 30842973; 30697589; 25701871
Phenotypes for Region: LMNB1 upstream region were set to Adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215
Regression v0.611 LMNB1 upstream region Sarah Milton Tag regulatory region was added to Region: LMNB1 upstream region.
Mendeliome v1.4728 LMNB1 upstream region Sarah Milton Tag regulatory region was added to Region: LMNB1 upstream region.
Hand and foot malformations v0.88 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Mendeliome v1.4727 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Craniosynostosis v1.85 IHH upstream regulatory region Sarah Milton Tag regulatory region was added to Region: IHH upstream regulatory region.
Pulmonary Arterial Hypertension v1.57 FOXF1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: FOXF1 upstream regulatory region.
Mendeliome v1.4726 FOXF1 upstream regulatory region Sarah Milton Tag regulatory region was added to Region: FOXF1 upstream regulatory region.
Fetal anomalies v1.558 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1, much larger deletions or disruption to the region from translocations/inversions may still be causative of disease
Sources: Literature
Hand and foot malformations v0.87 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Hand and foot malformations v0.86 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1 much larger deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Mendeliome v1.4725 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1 much larger deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Mendeliome v1.4725 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Hand and foot malformations v0.86 Sarah Milton Copied Region DLX5 downstream regulatory region from panel Mendeliome
Hand and foot malformations v0.86 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Hand and foot malformations. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Fetal anomalies v1.557 Sarah Milton Copied Region DLX5 downstream regulatory region from panel Mendeliome
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Fetal anomalies. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Mendeliome v1.4724 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Review for Region: DLX5 downstream regulatory region was set to GREEN
Added comment: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature
Glaucoma congenital v1.11 Chirag Patel Copied gene WDR36 from panel Mendeliome
Glaucoma congenital v1.11 WDR36 Chirag Patel gene: WDR36 was added
gene: WDR36 was added to Glaucoma congenital. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: WDR36.
Mode of inheritance for gene: WDR36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR36 were set to 15677485; 18172102; 20813748
Phenotypes for gene: WDR36 were set to Glaucoma 1, open angle, G, MIM# 609887
Monogenic Diabetes v0.224 DYRK1B Bryony Thompson Classified gene: DYRK1B as Green List (high evidence)
Monogenic Diabetes v0.224 DYRK1B Bryony Thompson Gene: dyrk1b has been classified as Green List (High Evidence).
Monogenic Diabetes v0.223 Bryony Thompson Added reviews for gene DYRK1B from panel Mendeliome
Mendeliome v1.4723 DYRK1B Bryony Thompson Classified gene: DYRK1B as Green List (high evidence)
Mendeliome v1.4723 DYRK1B Bryony Thompson Gene: dyrk1b has been classified as Green List (High Evidence).
Mendeliome v1.4722 DYRK1B Bryony Thompson reviewed gene: DYRK1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39192769, 38170957, 34786696, 34193236, 28743892; Phenotypes: abdominal obesity-metabolic syndrome 3, MONDO:0014352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Marked gene: DUOXA1 as ready
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Gene: duoxa1 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v1.43 DUOXA1 Bryony Thompson Phenotypes for gene: DUOXA1 were changed from congenital hypothyroidism MONDO:0018612 to Inborn error of immunity, MONDO:0003778
Disorders of immune dysregulation v1.42 DUOXA1 Bryony Thompson Mode of inheritance for gene: DUOXA1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v1.41 DUOXA1 Bryony Thompson edited their review of gene: DUOXA1: Changed publications: 36166305; Changed phenotypes: Inborn error of immunity, MONDO:0003778; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v1.41 Bryony Thompson Copied gene DUOXA1 from panel Mendeliome
Disorders of immune dysregulation v1.41 DUOXA1 Bryony Thompson gene: DUOXA1 was added
gene: DUOXA1 was added to Disorders of immune dysregulation. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: DUOXA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DUOXA1 were set to 29650690; 39988947; 36740391; 31428054
Phenotypes for gene: DUOXA1 were set to congenital hypothyroidism MONDO:0018612
Mendeliome v1.4722 DUOXA1 Bryony Thompson reviewed gene: DUOXA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36166305, 31428054, 29650690; Phenotypes: Inborn error of immunity, MONDO:0003778, congenital hypothyroidism MONDO:0018612; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.58 DROSHA Bryony Thompson Classified gene: DROSHA as Red List (low evidence)
Spontaneous coronary artery dissection v0.58 DROSHA Bryony Thompson Gene: drosha has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.57 DROSHA Bryony Thompson edited their review of gene: DROSHA: Changed rating: RED
Spontaneous coronary artery dissection v0.57 Bryony Thompson Copied gene DROSHA from panel Mendeliome
Spontaneous coronary artery dissection v0.57 DROSHA Bryony Thompson gene: DROSHA was added
gene: DROSHA was added to Spontaneous coronary artery dissection. Sources: Expert Review Amber,Literature
non-coding gene tags were added to gene: DROSHA.
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 39654947; 35405010; 29339534
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Hereditary Haemorrhagic Telangiectasia v1.6 Bryony Thompson Copied gene DROSHA from panel Mendeliome
Hereditary Haemorrhagic Telangiectasia v1.6 DROSHA Bryony Thompson gene: DROSHA was added
gene: DROSHA was added to Hereditary Haemorrhagic Telangiectasia. Sources: Expert Review Amber,Literature
non-coding gene tags were added to gene: DROSHA.
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 39654947; 35405010; 29339534
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Mendeliome v1.4722 DROSHA Bryony Thompson Phenotypes for gene: DROSHA were changed from Neurodevelopmental disorder (MONDO#0700092), DROSHA-related to Neurodevelopmental disorder, MONDO:0700092; hereditary hemorrhagic telangiectasia MONDO:0019180; idiopathic spontaneous coronary artery dissection MONDO:0007385
Mendeliome v1.4721 DROSHA Bryony Thompson Publications for gene: DROSHA were set to 35405010
Mendeliome v1.4720 DROSHA Bryony Thompson reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 39654947, 35405010, 29339534; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, hereditary hemorrhagic telangiectasia MONDO:0019180, idiopathic spontaneous coronary artery dissection MONDO:0007385; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Marked gene: DRD2 as ready
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Classified gene: DRD2 as Green List (high evidence)
Dystonia and Chorea v0.344 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.343 DRD2 Bryony Thompson edited their review of gene: DRD2: Added comment: PMIDs 33200438, 34145635 and 38643909 report 7 individuals from 3 unrelated families with monoallelic gain‑of‑function DRD2 missense variants presenting with a hyperkinetic movement‑disorder spectrum—from adolescent‑onset chorea with cervical dystonia to infancy‑onset severe motor, cognitive and neuropsychiatric deficits. Functional assays demonstrate constitutive G‑protein activation and reduced arrestin‑β‑arrestin recruitment; two de novo cases confirm dominant inheritance. PMID 36456191 reports a mouse model of I212F with a hyperkinetic movement disorder.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: 38643909, 34145635, 33974399, 33200438, 36456191
Mendeliome v1.4720 DRD2 Bryony Thompson Publications for gene: DRD2 were set to
Mendeliome v1.4719 DRD2 Bryony Thompson Classified gene: DRD2 as Green List (high evidence)
Mendeliome v1.4719 DRD2 Bryony Thompson Gene: drd2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.343 Bryony Thompson Added reviews for gene DRD2 from panel Mendeliome
Mendeliome v1.4718 DRD2 Bryony Thompson edited their review of gene: DRD2: Added comment: PMIDs 33200438, 34145635 and 38643909 report 7 individuals from 3 unrelated families with monoallelic gain‑of‑function DRD2 missense variants presenting with a hyperkinetic movement‑disorder spectrum—from adolescent‑onset chorea with cervical dystonia to infancy‑onset severe motor, cognitive and neuropsychiatric deficits. Functional assays demonstrate constitutive G‑protein activation and reduced arrestin‑β‑arrestin recruitment; two de novo cases confirm dominant inheritance.
PMID 36456191 reports a mouse model of I212F with a hyperkinetic movement disorder.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: 38643909, 34145635, 33974399, 33200438, 36456191; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Marked gene: DMRT1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Classified gene: DMRT1 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.410 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 DMRT1 Bryony Thompson edited their review of gene: DMRT1: Changed rating: AMBER
Differences of Sex Development v1.47 DMRT1 Bryony Thompson edited their review of gene: DMRT1: Changed rating: AMBER
Infertility and Recurrent Pregnancy Loss v1.140 DMRT1 Bryony Thompson Publications for gene: DMRT1 were set to 26139570; 38511217; 39777458
Infertility and Recurrent Pregnancy Loss v1.139 DMRT1 Bryony Thompson Classified gene: DMRT1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.139 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 Bryony Thompson Copied gene DMRT1 from panel Mendeliome
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.409 DMRT1 Bryony Thompson gene: DMRT1 was added
gene: DMRT1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DMRT1 were set to 40442410; 39777458; 38511217; 36572623; 35366911; 32741963; 31745530; 31479588; 26139570; 26005864
Phenotypes for gene: DMRT1 were set to 46,XY disorder of sex development, MONDO:0020040
Infertility and Recurrent Pregnancy Loss v1.138 Bryony Thompson Added reviews for gene DMRT1 from panel Mendeliome
Differences of Sex Development v1.47 Bryony Thompson Added reviews for gene DMRT1 from panel Mendeliome
Mendeliome v1.4718 DMRT1 Bryony Thompson Publications for gene: DMRT1 were set to 31479588; 24934491; 29527098
Mendeliome v1.4717 DMRT1 Bryony Thompson Classified gene: DMRT1 as Green List (high evidence)
Mendeliome v1.4717 DMRT1 Bryony Thompson Gene: dmrt1 has been classified as Green List (High Evidence).
Mendeliome v1.4716 DMRT1 Bryony Thompson reviewed gene: DMRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40442410, 39777458, 38511217, 36572623, 35366911, 32741963, 31745530, 31479588, 26139570, 26005864; Phenotypes: 46,XX disorder of sex development, MONDO:0017576, 46,XY disorder of sex development, MONDO:0020040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Marked gene: DLG2 as ready
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Gene: dlg2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.111 DLG2 Bryony Thompson Publications for gene: DLG2 were set to 37860969; 32341572
Hypogonadotropic hypogonadism v0.110 DLG2 Bryony Thompson Phenotypes for gene: DLG2 were changed from Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205 to delayed puberty, self-limited, MONDO:0859205
Hypogonadotropic hypogonadism v0.109 Bryony Thompson Copied gene DLG2 from panel Mendeliome
Hypogonadotropic hypogonadism v0.109 DLG2 Bryony Thompson gene: DLG2 was added
gene: DLG2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Literature
SV/CNV tags were added to gene: DLG2.
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to 37860969; 32341572
Phenotypes for gene: DLG2 were set to Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205
Mendeliome v1.4716 DLG2 Bryony Thompson Phenotypes for gene: DLG2 were changed from Intellectual disability (MONDO#0001071), DLG2-related to Intellectual disability (MONDO#0001071), DLG2-related; delayed puberty, self-limited, MONDO:0859205
Mendeliome v1.4715 DLG2 Bryony Thompson Publications for gene: DLG2 were set to PMID: 37860969
Mendeliome v1.4714 DLG2 Bryony Thompson Classified gene: DLG2 as Green List (high evidence)
Mendeliome v1.4714 DLG2 Bryony Thompson Gene: dlg2 has been classified as Green List (High Evidence).
Mendeliome v1.4713 DLG2 Bryony Thompson reviewed gene: DLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32341572; Phenotypes: delayed puberty, self-limited, MONDO:0859205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4713 Bryony Thompson Copied gene DIP2B from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.4713 DIP2B Bryony Thompson gene: DIP2B was added
gene: DIP2B was added to Mendeliome. Sources: Expert Review Red,Genetic Health Queensland
5'UTR tags were added to gene: DIP2B.
Mode of inheritance for gene: DIP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2B were set to 17236128; 33688487
Phenotypes for gene: DIP2B were set to Mental retardation, FRA12A type, MIM# 136630
Mode of pathogenicity for gene: DIP2B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v1.745 DIP2B Bryony Thompson Publications for gene: DIP2B were set to 17236128
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Classified gene: DIP2B as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Added comment: Comment on list classification: STR added as an STR
Intellectual disability syndromic and non-syndromic v1.744 DIP2B Bryony Thompson Gene: dip2b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.743 DIP2B Bryony Thompson Deleted their comment
Intellectual disability syndromic and non-syndromic v1.743 DIP2B Bryony Thompson edited their review of gene: DIP2B: Added comment: PMID 33688487 reports two siblings from one family with a heterozygous splice‑site loss‑of‑function DIP2B variant causing moderate intellectual disability.; Changed rating: RED; Changed publications: 33688487; Changed phenotypes: intellectual disability MONDO:0001071; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dyslipidaemia v0.51 CREB3L3 Bryony Thompson Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Dyslipidaemia v0.50 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Green List (high evidence)
Dyslipidaemia v0.50 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Green List (High Evidence).
Dyslipidaemia v0.49 CREB3L3 Bryony Thompson edited their review of gene: CREB3L3: Added comment: Recent studies expand the evidence base for CREB3L3. PMID 34491909 adds a cohort of ten unrelated adults with heterozygous loss‑of‑function or missense CREB3L3 variants who present with severe adult‑onset hypertriglyceridemia, detailed lipoprotein profiling, and mouse‑model rescue of the lipid phenotype. PMID 41099101 reports six additional heterozygous CREB3L3 carriers among patients with multifactorial chylomicronemia syndrome.; Changed rating: GREEN; Changed publications: 32580631, 29954705, 27982131, 27291420, 26427795, 21666694, 41099101, 34491909
Dyslipidaemia v0.49 Bryony Thompson Added reviews for gene CREB3L3 from panel Mendeliome
Mendeliome v1.4712 CREB3L3 Bryony Thompson Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Mendeliome v1.4711 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Green List (high evidence)
Mendeliome v1.4711 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Green List (High Evidence).
Mendeliome v1.4710 CREB3L3 Bryony Thompson edited their review of gene: CREB3L3: Added comment: Recent studies expand the evidence base for CREB3L3. PMID 34491909 adds a cohort of ten unrelated adults with heterozygous loss‑of‑function or missense CREB3L3 variants who present with severe adult‑onset hypertriglyceridemia, detailed lipoprotein profiling, and mouse‑model rescue of the lipid phenotype. PMID 41099101 reports six additional heterozygous CREB3L3 carriers among patients with multifactorial chylomicronemia syndrome.; Changed rating: GREEN; Changed publications: 41099101, 34491909, 26427795; Changed phenotypes: hypertriglyceridemia, MONDO:0005347; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Deafness_IsolatedAndComplex v1.359 COL4A6 Bryony Thompson Publications for gene: COL4A6 were set to 23714752; 33840813; 41092388
Deafness_IsolatedAndComplex v1.358 COL4A6 Bryony Thompson Classified gene: COL4A6 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.358 COL4A6 Bryony Thompson Gene: col4a6 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.357 Bryony Thompson Added reviews for gene COL4A6 from panel Mendeliome
Mendeliome v1.4710 COL4A6 Bryony Thompson Publications for gene: COL4A6 were set to 23714752; 12784310; 33840813
Mendeliome v1.4709 COL4A6 Bryony Thompson Mode of inheritance for gene: COL4A6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.4708 COL4A6 Bryony Thompson Classified gene: COL4A6 as Green List (high evidence)
Mendeliome v1.4708 COL4A6 Bryony Thompson Gene: col4a6 has been classified as Green List (High Evidence).
Mendeliome v1.4707 COL4A6 Bryony Thompson reviewed gene: COL4A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 41092388, 40928595, 23714752, 39272213, 33840813; Phenotypes: hearing loss, X-linked 6, MONDO:0010484; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.4707 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Mendeliome v1.4707 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.408 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Genetic Epilepsy v1.408 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.743 WDTC1 Zornitza Stark Marked gene: WDTC1 as ready
Intellectual disability syndromic and non-syndromic v1.743 WDTC1 Zornitza Stark Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Classified gene: ABCC9 as Amber List (moderate evidence)
Dilated Cardiomyopathy v1.66 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v1.19 PI4KA Zornitza Stark Marked gene: PI4KA as ready
Arthrogryposis v1.19 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Arthrogryposis v1.19 PI4KA Zornitza Stark Classified gene: PI4KA as Amber List (moderate evidence)
Arthrogryposis v1.19 PI4KA Zornitza Stark Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.84 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Craniosynostosis v1.84 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Craniosynostosis v1.84 CHD3 Zornitza Stark Classified gene: CHD3 as Green List (high evidence)
Craniosynostosis v1.84 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Craniosynostosis v1.83 CHD3 Zornitza Stark gene: CHD3 was added
gene: CHD3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to 37086723
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to GREEN
Added comment: PMID 37086723 reports three unrelated individuals with de novo heterozygous missense CHD3 variants in the helicase domain causing syndromic craniosynostosis (metopic/sagittal) with congenital onset. The variants are absent from population databases, segregation is confirmed de novo, and the paper identifies CHD3 as one of 13 genome‑wide significant craniosynostosis genes.
Sources: Literature
Craniosynostosis v1.82 KMT5B Zornitza Stark Marked gene: KMT5B as ready
Craniosynostosis v1.82 KMT5B Zornitza Stark Gene: kmt5b has been classified as Green List (High Evidence).
Craniosynostosis v1.82 KMT5B Zornitza Stark Classified gene: KMT5B as Green List (high evidence)
Craniosynostosis v1.82 KMT5B Zornitza Stark Gene: kmt5b has been classified as Green List (High Evidence).
Craniosynostosis v1.81 KMT5B Zornitza Stark edited their review of gene: KMT5B: Changed rating: GREEN
Craniosynostosis v1.81 KMT5B Zornitza Stark gene: KMT5B was added
gene: KMT5B was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT5B were set to 37086723
Phenotypes for gene: KMT5B were set to Intellectual developmental disorder, autosomal dominant 51 MIM# 617788
Added comment: PMID 37086723 reports 3 individuals from 3 unrelated families with heterozygous de novo loss‑of‑function (2 frameshift) or missense KMT5B variants presenting with syndromic craniosynostosis (metopic) with congenital onset. Variants are absent from population databases; de novo segregation confirmed.
Sources: Literature
Craniosynostosis v1.80 JAG1 Zornitza Stark Publications for gene: JAG1 were set to 29530693; 12244552
Craniosynostosis v1.79 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Craniosynostosis v1.79 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Craniosynostosis v1.78 JAG1 Zornitza Stark edited their review of gene: JAG1: Added comment: PMID 39742518 reports 6 individuals from 5 unrelated families with heterozygous loss-of-function JAG1 variants presenting with pediatric-onset craniosynostosis in the context of Alagille syndrome.; Changed rating: GREEN; Changed publications: 29530693, 12244552, 39742518; Changed phenotypes: Alagille syndrome 1, MIM# 118450
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Classified gene: AIFM1 as Green List (high evidence)
Skeletal dysplasia v0.430 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.429 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 33439541; 28842795; 27102849
Phenotypes for gene: AIFM1 were set to spondyloepimetaphyseal dysplasia, Bieganski type, MONDO:0010275; Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, MIM# 300232
Review for gene: AIFM1 was set to GREEN
Added comment: PMID 28842795 reports 12 affected males from 6 unrelated families with X‑linked AIFM1 variants; PMID 27102849 reports 7 affected males from 2 unrelated families with the recurrent p.Asp237Gly variant; PMID 33439541 adds 2 affected males from 2 families (one novel intronic splice variant, one previously reported synonymous variant). All cases present with short stature, kyphoscoliosis, spondylometaphyseal dysplasia, cerebral hypomyelination, motor delay and progressive neurodegeneration. Functional studies show reduced AIFM1 mRNA/protein and exon‑7 skipping, supporting loss‑of‑function. X‑linked recessive inheritance with carrier mothers (occasionally mosaic) is consistently reported.
Sources: Literature
Craniosynostosis v1.78 ADNP Zornitza Stark Marked gene: ADNP as ready
Craniosynostosis v1.78 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Craniosynostosis v1.78 ADNP Zornitza Stark Classified gene: ADNP as Green List (high evidence)
Craniosynostosis v1.78 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Craniosynostosis v1.77 ADNP Zornitza Stark gene: ADNP was added
gene: ADNP was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 37086723
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome MIM#615873
Review for gene: ADNP was set to GREEN
Added comment: PMID 37086723 reports 3 individuals from 3 unrelated families with heterozygous de novo loss-of-function ADNP variants presenting with syndromic craniosynostosis (sagittal or metopic) of congenital onset.
Sources: Literature
Prepair 1000+ v2.16 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly-micromelia syndrome (MIM#251230); Microcephaly, short stature, and limb abnormalities (MIM#617604) to Microcephaly-micromelia syndrome (MIM#251230); Microcephaly, short stature, and limb abnormalities (MIM#617604); Meier-Gorlin syndrome 10, MIM# 621528
Fetal anomalies v1.556 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Skeletal dysplasia v0.428 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; Meier-Gorlin syndrome 10, MIM# 621528
Skeletal dysplasia v0.427 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, Meier-Gorlin syndrome 10, MIM# 621528
Microcephaly v1.427 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619; Meier-Gorlin syndrome 10, MIM# 621528
Microcephaly v1.426 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4707 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619; Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4706 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Skeletal Dysplasia_Fetal v0.246 DONSON Zornitza Stark edited their review of gene: DONSON: Changed phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230, MONDO:0009619, Meier-Gorlin syndrome 10, MIM# 621528
Mendeliome v1.4706 ASNA1 Sangavi Sivagnanasundram Tag new gene name tag was added to gene: ASNA1.
Mendeliome v1.4706 ASNA1 Sangavi Sivagnanasundram reviewed gene: ASNA1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008925; Phenotypes: cardiomyopathy, dilated, 2H MONDO:0859358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4706 GATAD1 Sangavi Sivagnanasundram reviewed gene: GATAD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy 2B MONDO:0013848; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4706 ABCC9 Sangavi Sivagnanasundram changed review comment from: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA, gene remain as AMBER given the two reports in affected individuals.
Sources: ClinGen; to: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA relating to DCM, gene remain as AMBER for DCM given the two reports in affected individuals.

GREEN association for Hypertrichotic osteochondrodysplasia Cantu type.

Sources: ClinGen
Mendeliome v1.4706 Sangavi Sivagnanasundram Added reviews for gene ABCC9 from panel Dilated Cardiomyopathy
Dilated Cardiomyopathy v1.65 ABCC9 Sangavi Sivagnanasundram gene: ABCC9 was added
gene: ABCC9 was added to Dilated Cardiomyopathy. Sources: ClinGen
Mode of inheritance for gene: ABCC9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC9 were set to 15034580
Phenotypes for gene: ABCC9 were set to dilated cardiomyopathy 1O MONDO:0012062
Review for gene: ABCC9 was set to AMBER
Added comment: LIMITED classified by ClinGen Dilated Cardiomyopathy GCEP on 04/03/2026 - https://search.clinicalgenome.org/CCID:004012

Two individuals reported with heart failure and idiopathic dilated cardiomyopathy with rare missense and frameshift variants. ClinGen also reports animal models however given the uncertainty of the GDA, gene remain as AMBER given the two reports in affected individuals.
Sources: ClinGen
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Deleted their comment
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel commented on gene: NKX2-1: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Marked gene: NKX2-1 as ready
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.108 NKX2-1 Chirag Patel Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Hypogonadotropic hypogonadism v0.107 NKX2-1 Chirag Patel Phenotypes for gene: NKX2-1 were changed from NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.208 NKX2-1 Chirag Patel Phenotypes for gene: NKX2-1 were changed from NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.207 NKX2-1 Chirag Patel Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Pituitary hormone deficiency v0.206 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Pituitary hormone deficiency v0.206 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel edited their review of gene: NKX2-1: Added comment: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.; Changed rating: RED; Changed publications: 33270637, 30186310; Changed phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Pituitary hormone deficiency v0.205 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.106 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.106 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.105 NKX2-1 Chirag Patel Classified gene: NKX2-1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.105 NKX2-1 Chirag Patel Gene: nkx2-1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.104 NKX2-1 Chirag Patel edited their review of gene: NKX2-1: Added comment: PMID 30186310 reports 2 affected individuals (father-daughter) from 1 unrelated family (heterozygous nonsense variant - c.338G>A p.Trp113*) presenting with hypogonadotropic hypogonadism and growth‑hormone deficiency. PMID 33270637 reports 1 affected individual (heterozygous missense variant - c.67G>C) with pituitary stalk interruption syndrome, choreoathetosis and hypogonadotropic hypogonadism. No segregation data for 2nd case. No functional validation for both variants.; Changed rating: RED; Changed publications: 33270637, 30186310; Changed phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520
Pituitary hormone deficiency v0.204 Chirag Patel Copied gene NKX2-1 from panel Mendeliome
Pituitary hormone deficiency v0.204 NKX2-1 Chirag Patel gene: NKX2-1 was added
gene: NKX2-1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Phenotypes for gene: NKX2-1 were set to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Hypogonadotropic hypogonadism v0.104 Chirag Patel Copied gene NKX2-1 from panel Mendeliome
Hypogonadotropic hypogonadism v0.104 NKX2-1 Chirag Patel gene: NKX2-1 was added
gene: NKX2-1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Royal Melbourne Hospital,Victorian Clinical Genetics Services
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Phenotypes for gene: NKX2-1 were set to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v1.4705 Chirag Patel Added reviews for gene NKX2-1 from panel Intellectual disability syndromic and non-syndromic
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v1.202 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.556 NKX2-1 Chirag Patel Mode of inheritance for gene: NKX2-1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.203 Chirag Patel Copied gene ARHGAP5 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.203 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Mendeliome v1.4704 Chirag Patel Copied gene ARHGAP5 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4704 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel Marked gene: ARHGAP5 as ready
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel Gene: arhgap5 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.103 ARHGAP5 Chirag Patel gene: ARHGAP5 was added
gene: ARHGAP5 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: ARHGAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP5 were set to 39308770; 36178483
Phenotypes for gene: ARHGAP5 were set to Kallmann syndrome MONDO:0018800
Review for gene: ARHGAP5 was set to RED
Added comment: PMID 36178483 reports 2 individuals from 2 unrelated families with heterozygous truncating variants in ARHGAP5 (p.Phe790Ilefs*2, p.Tyr502Metfs*3) presenting with hypogonadotropic hypogonadism/Kallmann syndrome (childhood onset, anosmia). One variant was de novo and the other had unknown parental status. Functional zebrafish modeling showed no robust GnRH phenotype.

PMID 39308770 reported 1 patient with hypogonadotropic hypogonadism and a heterozygous ARHGAP5 variant (p.Val269Leu - classified as VUS) but provided no detailed phenotype, segregation or functional data.
Sources: Literature
Pituitary hormone deficiency v0.202 AMH Chirag Patel Marked gene: AMH as ready
Pituitary hormone deficiency v0.202 AMH Chirag Patel Gene: amh has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.202 Chirag Patel Copied gene AMH from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.202 AMH Chirag Patel gene: AMH was added
gene: AMH was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: AMH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AMH were set to 31291191
Phenotypes for gene: AMH were set to Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4703 AMH Chirag Patel Mode of inheritance for gene: AMH was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4702 AMH Chirag Patel Phenotypes for gene: AMH were changed from Persistent Mullerian duct syndrome, type I (MIM#261550) to Persistent Mullerian duct syndrome, type I (MIM#261550); Hypogonadotropic hypogonadism, MONDO:0018555
Mendeliome v1.4701 AMH Chirag Patel Publications for gene: AMH were set to 32172781; 31291191
Mendeliome v1.4701 AMH Chirag Patel Publications for gene: AMH were set to 32172781
Mendeliome v1.4700 AMH Chirag Patel Mode of inheritance for gene: AMH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4699 Chirag Patel Added reviews for gene AMH from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.102 AMH Chirag Patel Classified gene: AMH as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v0.102 AMH Chirag Patel Gene: amh has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel Marked gene: AMH as ready
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel Gene: amh has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.101 AMH Chirag Patel gene: AMH was added
gene: AMH was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: AMH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AMH were set to 31291191
Phenotypes for gene: AMH were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: AMH was set to AMBER
Added comment: PMID 31291191 reports 3 individuals from 3 unrelated families with heterozygous missense variants in AMH gene (p.Thr99Ser, p.Pro151Ser, p.Asp238Glu). They presented with childhood‑onset hypogonadotropic hypogonadism (CHH) often with variable anosmia (Kallmann syndrome). Two variants were inherited from an affected parent, and 1 variant had unknown parental status. Functional studies demonstrated significantly reduced AMH secretion in transfected COS-7 cells, impaired GnRH‑neuron migration, and decreased GnRH release. AMH is expressed in migratory GnRH neurons in both mouse and human fetuses.
Sources: Literature
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel Marked gene: SOX11 as ready
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel Gene: sox11 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.201 Chirag Patel Copied gene SOX11 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.201 SOX11 Chirag Patel gene: SOX11 was added
gene: SOX11 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert Review,Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Mendeliome v1.4698 ACTL6A Sangavi Sivagnanasundram reviewed gene: ACTL6A: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004045; Phenotypes: ACTL6A-related BAFopathy MONDO:0700121; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.200 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Mendeliome v1.4698 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Differences of Sex Development v1.46 Chirag Patel Added reviews for gene NDNF from panel Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism v0.100 NDNF Chirag Patel reviewed gene: NDNF: Rating: AMBER; Mode of pathogenicity: None; Publications: 36245975; Phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.120 IYD Chirag Patel Phenotypes for gene: IYD were changed from Thyroid dyshormonogenesis 4, MIM# 274800 to Thyroid dyshormonogenesis 4, MIM# 274800
Congenital hypothyroidism v0.119 IYD Chirag Patel Phenotypes for gene: IYD were changed from childhood/adolescent onset hypothyroidism; Thyroid dyshormonogenesis 4, 274800; normal iodide organification; Congenital hypothyroidism; raised urinary MIT and DIT; goitre to Thyroid dyshormonogenesis 4, MIM# 274800
Congenital hypothyroidism v0.118 IYD Chirag Patel Mode of inheritance for gene: IYD was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4697 Chirag Patel Added reviews for gene IYD from panel Congenital hypothyroidism
Congenital hypothyroidism v0.117 IYD Chirag Patel Marked gene: IYD as ready
Congenital hypothyroidism v0.117 IYD Chirag Patel Gene: iyd has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.117 IYD Chirag Patel reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: 39106437, 36633921; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.555 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Fetal anomalies v1.554 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.743 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Intellectual disability syndromic and non-syndromic v1.742 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.593 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Callosome v0.592 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.408 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Genetic Epilepsy v1.407 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.122 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Muscular dystrophy and myopathy_Paediatric v1.121 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.426 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Microcephaly v1.425 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4696 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Mendeliome v1.4695 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.100 WSB2 Zornitza Stark Phenotypes for gene: WSB2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, WSB2-related to Luo-Agrawal neurodevelopmental syndrome, MIM# 621552
Cerebellar and Pontocerebellar Hypoplasia v1.99 WSB2 Zornitza Stark reviewed gene: WSB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Luo-Agrawal neurodevelopmental syndrome, MIM# 621552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4695 CADM3 Sangavi Sivagnanasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:009251; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2FF MONDO:0030433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4695 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel changed review comment from: PMID 41830586 reports 4 individuals from 4 families with heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature; to: PMID 41830586 reports 4 individuals from 4 families with rare heterozygous missense KCNJ4 variants presenting with refractory epilepsy and neurodevelopmental delay/intellectual disability. Clinical features range from isolated epilepsy to severe developmental and epileptic encephalopathy. Two variants arose de novo and two had unknown segregation status. Electrophysiology in Xenopus oocytes demonstrates variant‑specific gain‑of‑function (Gly136Ser and Glu384Lys) or loss‑of‑function effects (Val206Met and Met293Lys).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.742 Chirag Patel Copied gene KCNJ4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.742 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KCNJ4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ4 were set to 41830586
Phenotypes for gene: KCNJ4 were set to Neurodevelopmental disorder, MONDO:0700092, KCNJ4-related
Mode of pathogenicity for gene: KCNJ4 was set to Other
Genetic Epilepsy v1.407 Chirag Patel Copied gene KCNJ4 from panel Mendeliome