PanelApp (test)

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Genetic Epilepsy v1.407 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Genetic Epilepsy. 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
Mendeliome v1.4695 KCNJ4 Chirag Patel Marked gene: KCNJ4 as ready
Mendeliome v1.4695 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Mendeliome v1.4695 KCNJ4 Chirag Patel Classified gene: KCNJ4 as Green List (high evidence)
Mendeliome v1.4695 KCNJ4 Chirag Patel Gene: kcnj4 has been classified as Green List (High Evidence).
Mendeliome v1.4694 KCNJ4 Chirag Patel gene: KCNJ4 was added
gene: KCNJ4 was added to Mendeliome. Sources: 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
Review for gene: KCNJ4 was set to GREEN
Added comment: 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
Congenital Disorders of Glycosylation v1.85 Sarah Milton Added reviews for gene PIGM from panel Mendeliome
Overgrowth v1.21 Lucy Spencer Added reviews for gene SPIN4 from panel Mendeliome
Mendeliome v1.4693 SPIN4 Lucy Spencer reviewed gene: SPIN4: Rating: AMBER; Mode of pathogenicity: None; Publications: Lui-Jee-Baron syndrome MIM#301114; Phenotypes: 41780720, 41158422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v1.741 Lucy Spencer Copied gene WDTC1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.741 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Genetic Epilepsy v1.406 Lucy Spencer Copied gene WDTC1 from panel Mendeliome
Genetic Epilepsy v1.406 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Mendeliome v1.4693 WDTC1 Lucy Spencer Classified gene: WDTC1 as Amber List (moderate evidence)
Mendeliome v1.4693 WDTC1 Lucy Spencer Gene: wdtc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4692 WDTC1 Lucy Spencer gene: WDTC1 was added
gene: WDTC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDTC1 were set to 41793087
Phenotypes for gene: WDTC1 were set to Neurodevelopmental disorder MONDO:0700092, WDTC1-related
Review for gene: WDTC1 was set to AMBER
Added comment: PMID 41793087 reports 7 individuals from 6 unrelated families with heterozygous variants in WDTC1. 1 from the DDD study. 3 missense, 2 PTCs, 1 canonical splice. 2 missense and 1 PTC were de novo, no inheritance info for the splice. The other PTC was inherited from an affected mother (mild ID and seizures), and the other missense was paternally inherited from an unaffected father- this variant Arg675Gln also has 15 hets in gnomad. The other 2 missense are also present in gnomad with 2 and 7 hets, while the PTC and splice variants are absent or only have 1 het (PTCS in general are also rare in gnomad in this gene).

The features in these probands were quite general- developmental delay, intellectual disability, seizures and variable additional features such as autism, ADHD and facial dysmorphism. No experimental functional validation was provided.

Only counting the PTCs and splice due to the gnomad counts for the missense we have 4 patients from 3 families, only 1 de novo, 1 inherited from a mildly affected mother and all with a very general phenotype with no experimental evidence. Keeping as amber for the moment
Sources: Literature
Monogenic Diabetes v0.222 APPL1 Sangavi Sivagnanasundram Tag refuted tag was added to gene: APPL1.
Monogenic Diabetes v0.222 Sangavi Sivagnanasundram Added reviews for gene APPL1 from panel Mendeliome
Mendeliome v1.4691 APPL1 Sangavi Sivagnanasundram Tag refuted tag was added to gene: APPL1.
Mendeliome v1.4691 APPL1 Sangavi Sivagnanasundram reviewed gene: APPL1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004159; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4691 NME8 Sangavi Sivagnanasundram Phenotypes for gene: NME8 were changed from Ciliary dyskinesia, primary, 6, MIM# 610852 to Ciliary dyskinesia, primary, 6, MIM# 610852; primary ciliary dyskinesia MONDO:0016575
Mendeliome v1.4690 NME8 Sangavi Sivagnanasundram Added comment: Comment on phenotypes: primary ciliary dyskinesia MONDO:0016575
Mendeliome v1.4690 NME8 Sangavi Sivagnanasundram Phenotypes for gene: NME8 were changed from Ciliary dyskinesia, primary, 6, MIM# 610852 to Ciliary dyskinesia, primary, 6, MIM# 610852
Mendeliome v1.4689 NME8 Sangavi Sivagnanasundram Tag disputed tag was added to gene: NME8.
Mendeliome v1.4689 NME8 Sangavi Sivagnanasundram reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005652; Phenotypes: primary ciliary dyskinesia MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4689 PIGM Sarah Milton reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 41782195, 39912323, 39425582, 39119839, 31445883; Phenotypes: hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency, MONDO:0012465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.64 SLC6A6 Lucy Spencer edited their review of gene: SLC6A6: Changed rating: AMBER
Dilated Cardiomyopathy v1.64 SLC6A6 Lucy Spencer changed review comment from: This gene was reviewed as limited by ClinGen in 2023 however PMID: 41343195 had not yet been published at that time

PMID: 41343195 four families with Leber congenital amaurosis or early-onset retinal dystrophy, all have homozygous variants in SLC6A6- 2 missense, 1 in frame del, 1 nonsense. Thr249Ile, Ala294Thr, Phe404_Glu449del, Trp113Ter. in 1 family the variant segregated with disease as homozygous in 4 affected siblings and heterozygous in unaffected siblings. Some functional evidence available for the 2 missense demonstrating LOF effects. No clear cardiac phenotype was observed in these families.

PMIDs: 31345061, 31903486 reported Ala78Glu and Gly399Val homozygous; to: This gene was reviewed as limited by ClinGen in 2023 however PMID: 41343195 had not yet been published at that time

PMID: 41343195 four families with Leber congenital amaurosis or early-onset retinal dystrophy, all have homozygous variants in SLC6A6- 2 missense, 1 in frame del, 1 nonsense. Thr249Ile, Ala294Thr, Phe404_Glu449del, Trp113Ter. in 1 family the variant segregated with disease as homozygous in 4 affected siblings and heterozygous in unaffected siblings. Some functional evidence available for the 2 missense demonstrating LOF effects. No clear cardiac phenotype was observed in these families- still amber for the cardiac association

PMIDs: 31345061, 31903486 reported Ala78Glu and Gly399Val homozygous
Dilated Cardiomyopathy v1.64 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Aminoacidopathy v1.143 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from hypotaurinemic retinal degeneration and cardiomyopathy MONDO:0007777 to Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350
Aminoacidopathy v1.142 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31903486; 31345061
Aminoacidopathy v1.141 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Aminoacidopathy v1.141 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.67 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Cone-rod Dystrophy v0.66 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Cone-rod retinopathy; cardiomyopathy to Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350
Cone-rod Dystrophy v0.65 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Cone-rod Dystrophy v0.65 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Mendeliome v1.4689 SLC6A6 Lucy Spencer Phenotypes for gene: SLC6A6 were changed from Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy MIM#145350
Mendeliome v1.4688 SLC6A6 Lucy Spencer Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Mendeliome v1.4687 SLC6A6 Lucy Spencer Classified gene: SLC6A6 as Green List (high evidence)
Mendeliome v1.4687 SLC6A6 Lucy Spencer Gene: slc6a6 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.64 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Aminoacidopathy v1.140 Lucy Spencer Added reviews for gene SLC6A6 from panel Mendeliome
Mendeliome v1.4686 SLC6A6 Lucy Spencer reviewed gene: SLC6A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 41343195; Phenotypes: Hypotaurinemic retinal degeneration and cardiomyopathy MMI#145350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.740 SLC6A17 Lucy Spencer Publications for gene: SLC6A17 were set to 25704603; 23672601
Intellectual disability syndromic and non-syndromic v1.739 SLC6A17 Lucy Spencer Classified gene: SLC6A17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.739 SLC6A17 Lucy Spencer Gene: slc6a17 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.738 Lucy Spencer Added reviews for gene SLC6A17 from panel Mendeliome
Growth failure v1.102 Lucy Spencer Copied gene SLC6A17 from panel Mendeliome
Growth failure v1.102 SLC6A17 Lucy Spencer gene: SLC6A17 was added
gene: SLC6A17 was added to Growth failure. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC6A17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A17 were set to 25704603; 23672601; 40897375
Phenotypes for gene: SLC6A17 were set to Intellectual developmental disorder, autosomal recessive 48, MIM# 616269
Mendeliome v1.4686 SLC6A17 Lucy Spencer Publications for gene: SLC6A17 were set to 25704603; 23672601
Mendeliome v1.4685 SLC6A17 Lucy Spencer Classified gene: SLC6A17 as Green List (high evidence)
Mendeliome v1.4685 SLC6A17 Lucy Spencer Gene: slc6a17 has been classified as Green List (High Evidence).
Mendeliome v1.4684 SLC6A17 Lucy Spencer reviewed gene: SLC6A17: Rating: GREEN; Mode of pathogenicity: None; Publications: 25704603, 40897375; Phenotypes: Intellectual developmental disorder, autosomal recessive 48 MIM#616269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.737 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from pontocerebellar hypoplasia type 2A MONDO:0010190 to Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753
Intellectual disability syndromic and non-syndromic v1.736 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to 20301773
Intellectual disability syndromic and non-syndromic v1.735 TSEN54 Zornitza Stark Deleted their comment
Intellectual disability syndromic and non-syndromic v1.735 Zornitza Stark Added reviews for gene TSEN54 from panel Mendeliome
Mendeliome v1.4684 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753; Ataxia to Pontocerebellar hypoplasia type 2A 277470; Pontocerebellar hypoplasia type 4 225753
Mendeliome v1.4683 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to 24938831
Mendeliome v1.4682 TSEN54 Zornitza Stark edited their review of gene: TSEN54: Added comment: Reports from PMID 32697043, PMID 35962274, PMID 41825724, PMID 32214227, PMID 39400946, PMID 39634246, PMID 38347586, PMID 39034883, PMID 29410950, PMID 27570394, and PMID 34085948 add a total of 30 patients from 28 unrelated families with autosomal recessive TSEN54 variants (predominantly the founder missense c.919G>T) causing pontocerebellar hypoplasia with microcephaly, severe developmental delay, seizures and characteristic cerebellar‑pontine hypoplasia. PMID 39034883 provides functional validation using patient‑derived iPSC organoids that recapitulate the neuroanatomical phenotype.

MOI changed to biallelic as evidence for mono allelic association is very limited.; Changed publications: 41825724, 39634246, 39400946, 39034883, 38622473, 38347586, 35962274, 34085948, 32697043, 32214227, 29410950, 27570394, 27430971; Changed phenotypes: Pontocerebellar hypoplasia type 2A 277470, Pontocerebellar hypoplasia type 4 225753
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Ataxia v1.201 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Ataxia v1.201 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Genetic Epilepsy v1.405 MT-TY Zornitza Stark Marked gene: MT-TY as ready
Genetic Epilepsy v1.405 MT-TY Zornitza Stark Gene: mt-ty has been classified as Green List (High Evidence).
Mitochondrial disease v1.16 MT-TY Zornitza Stark Tag somatic was removed from gene: MT-TY.
Syndromic Retinopathy v0.256 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Syndromic Retinopathy v0.256 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Rhabdomyolysis and Metabolic Myopathy v1.46 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Rhabdomyolysis and Metabolic Myopathy v1.46 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Hereditary Neuropathy v1.190 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Hereditary Neuropathy v1.190 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Genetic Epilepsy v1.405 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Genetic Epilepsy v1.405 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Deafness_IsolatedAndComplex v1.356 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Deafness_IsolatedAndComplex v1.356 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Ataxia v1.201 Zornitza Stark Copied gene MT-TY from panel Mendeliome
Ataxia v1.201 MT-TY Zornitza Stark gene: MT-TY was added
gene: MT-TY was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TY.
Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL
Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411
Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Monogenic Diabetes v0.221 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Monogenic Diabetes v0.221 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Dystonia and Chorea v0.342 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Dystonia and Chorea v0.342 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Ataxia v1.200 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Ataxia v1.200 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Regression v0.610 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Regression v0.610 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Genetic Epilepsy v1.404 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Genetic Epilepsy v1.404 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Optic Atrophy v1.72 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Optic Atrophy v1.72 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Microcephaly v1.425 MT-TW Zornitza Stark Marked gene: MT-TW as ready
Microcephaly v1.425 MT-TW Zornitza Stark Gene: mt-tw has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.255 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Syndromic Retinopathy v0.255 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Regression v0.610 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Regression v0.610 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Regression. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Optic Atrophy v1.72 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Optic Atrophy v1.72 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Monogenic Diabetes v0.221 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Monogenic Diabetes v0.221 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Microcephaly v1.425 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Microcephaly v1.425 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Microcephaly. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Intellectual disability syndromic and non-syndromic v1.734 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.734 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Hereditary Neuropathy v1.189 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Hereditary Neuropathy v1.189 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Genetic Epilepsy v1.404 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Genetic Epilepsy v1.404 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Dystonia and Chorea v0.342 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Dystonia and Chorea v0.342 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Dystonia and Chorea. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Deafness_IsolatedAndComplex v1.355 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.355 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Cardiomyopathy_Paediatric v0.229 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.229 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Ataxia v1.200 Zornitza Stark Copied gene MT-TW from panel Mitochondrial disease
Ataxia v1.200 MT-TW Zornitza Stark gene: MT-TW was added
gene: MT-TW was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TW.
Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL
Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556
Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Monogenic Diabetes v0.220 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Monogenic Diabetes v0.220 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Dystonia and Chorea v0.341 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Dystonia and Chorea v0.341 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Ataxia v1.199 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Ataxia v1.199 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Regression v0.609 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Regression v0.609 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Genetic Epilepsy v1.403 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Genetic Epilepsy v1.403 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Cataract v1.3 MT-TV Zornitza Stark Marked gene: MT-TV as ready
Cataract v1.3 MT-TV Zornitza Stark Gene: mt-tv has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.45 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.45 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Regression v0.609 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Regression v0.609 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Regression. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Monogenic Diabetes v0.220 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Monogenic Diabetes v0.220 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Intellectual disability syndromic and non-syndromic v1.733 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.733 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Hereditary Neuropathy v1.188 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Hereditary Neuropathy v1.188 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Genetic Epilepsy v1.403 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Genetic Epilepsy v1.403 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Dystonia and Chorea v0.341 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Dystonia and Chorea v0.341 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Dystonia and Chorea. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Deafness_IsolatedAndComplex v1.354 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.354 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Cataract v1.3 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Cataract v1.3 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Cataract. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Cardiomyopathy_Paediatric v0.228 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.228 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Ataxia v1.199 Zornitza Stark Copied gene MT-TV from panel Mitochondrial disease
Ataxia v1.199 MT-TV Zornitza Stark gene: MT-TV was added
gene: MT-TV was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TV.
Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL
Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472; 39468830
Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Monogenic Diabetes v0.219 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Monogenic Diabetes v0.219 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Genetic Epilepsy v1.402 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Genetic Epilepsy v1.402 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Optic Atrophy v1.71 MT-TT Zornitza Stark Marked gene: MT-TT as ready
Optic Atrophy v1.71 MT-TT Zornitza Stark Gene: mt-tt has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.254 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Syndromic Retinopathy v0.254 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Rhabdomyolysis and Metabolic Myopathy v1.44 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.44 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Optic Atrophy v1.71 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Optic Atrophy v1.71 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Monogenic Diabetes v0.219 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Monogenic Diabetes v0.219 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Genetic Epilepsy v1.402 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Genetic Epilepsy v1.402 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Deafness_IsolatedAndComplex v1.353 Zornitza Stark Copied gene MT-TT from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.353 MT-TT Zornitza Stark gene: MT-TT was added
gene: MT-TT was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TT.
Mode of inheritance for gene gene: MT-TT was set to MITOCHONDRIAL
Publications for gene: MT-TT were set to 32083134; 8769114; 9367299; 1645537; 8511015; 22638997; 29760464; 30236074; 28187756; 35808913
Phenotypes for gene: MT-TT were set to Mitochondrial disease (MONDO:0044970), MT-TT-related
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Ataxia v1.198 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Ataxia v1.198 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Cataract v1.2 MT-TS2 Zornitza Stark Marked gene: MT-TS2 as ready
Cataract v1.2 MT-TS2 Zornitza Stark Gene: mt-ts2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.253 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Syndromic Retinopathy v0.253 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Monogenic Diabetes v0.218 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Monogenic Diabetes v0.218 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Monogenic Diabetes. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Intellectual disability syndromic and non-syndromic v1.732 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.732 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Hypogonadotropic hypogonadism v0.100 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Hypogonadotropic hypogonadism v0.100 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Genetic Epilepsy v1.401 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Genetic Epilepsy v1.401 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Deafness_IsolatedAndComplex v1.352 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.352 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Cataract v1.2 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Cataract v1.2 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Cataract. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Cardiomyopathy_Paediatric v0.227 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.227 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Ataxia v1.198 Zornitza Stark Copied gene MT-TS2 from panel Mitochondrial disease
Ataxia v1.198 MT-TS2 Zornitza Stark gene: MT-TS2 was added
gene: MT-TS2 was added to Ataxia. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS2.
Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL
Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285
Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related
Stroke v1.48 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Stroke v1.48 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark Marked gene: MT-TS1 as ready
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark Gene: mt-ts1 has been classified as Green List (High Evidence).
Stroke v1.48 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Stroke v1.48 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Stroke. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Rhabdomyolysis and Metabolic Myopathy v1.43 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.43 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Intellectual disability syndromic and non-syndromic v1.731 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.731 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Genetic Epilepsy v1.400 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Genetic Epilepsy v1.400 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Deafness_IsolatedAndComplex v1.351 Zornitza Stark Copied gene MT-TS1 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.351 MT-TS1 Zornitza Stark gene: MT-TS1 was added
gene: MT-TS1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TS1.
Mode of inheritance for gene gene: MT-TS1 was set to MITOCHONDRIAL
Publications for gene: MT-TS1 were set to 7669057; 9778262; 14605505; 23696415; 33279600; 7581383
Phenotypes for gene: MT-TS1 were set to Mitochondrial disease (MONDO:0044970), MT-TS1-related
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Genetic Epilepsy v1.399 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Genetic Epilepsy v1.399 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Optic Atrophy v1.70 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Optic Atrophy v1.70 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.252 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Syndromic Retinopathy v0.252 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Syndromic Retinopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Rhabdomyolysis and Metabolic Myopathy v1.42 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.42 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Optic Atrophy v1.70 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Optic Atrophy v1.70 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Optic Atrophy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Intellectual disability syndromic and non-syndromic v1.730 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Intellectual disability syndromic and non-syndromic v1.730 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Genetic Epilepsy v1.399 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Genetic Epilepsy v1.399 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Genetic Epilepsy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Cardiomyopathy_Paediatric v0.226 Zornitza Stark Copied gene MT-TR from panel Mitochondrial disease
Cardiomyopathy_Paediatric v0.226 MT-TR Zornitza Stark gene: MT-TR was added
gene: MT-TR was added to Cardiomyopathy_Paediatric. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TR.
Mode of inheritance for gene gene: MT-TR was set to MITOCHONDRIAL
Publications for gene: MT-TR were set to 15286228; 17588757; 19809478; 22781096
Phenotypes for gene: MT-TR were set to mitochondrial disease (MONDO:0044970), MT-TR-related
Stroke v1.47 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Stroke v1.47 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.69 MT-TQ Zornitza Stark Marked gene: MT-TQ as ready
Optic Atrophy v1.69 MT-TQ Zornitza Stark Gene: mt-tq has been classified as Amber List (Moderate Evidence).
Stroke v1.47 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Stroke v1.47 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Stroke. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Rhabdomyolysis and Metabolic Myopathy v1.41 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.41 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Optic Atrophy v1.69 Zornitza Stark Copied gene MT-TQ from panel Mitochondrial disease
Optic Atrophy v1.69 MT-TQ Zornitza Stark gene: MT-TQ was added
gene: MT-TQ was added to Optic Atrophy. Sources: Expert Review Amber,Expert list
mtDNA tags were added to gene: MT-TQ.
Mode of inheritance for gene gene: MT-TQ was set to MITOCHONDRIAL
Publications for gene: MT-TQ were set to 11171912; 10996779; 17003408; 11335700
Phenotypes for gene: MT-TQ were set to Mitochondrial disease (MONDO:0044970), MT-TQ-related
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark Marked gene: MT-TL2 as ready
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark Gene: mt-tl2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.40 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.40 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Hereditary Neuropathy v1.187 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Hereditary Neuropathy v1.187 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Deafness_IsolatedAndComplex v1.350 Zornitza Stark Copied gene MT-TL2 from panel Mitochondrial disease
Deafness_IsolatedAndComplex v1.350 MT-TL2 Zornitza Stark gene: MT-TL2 was added
gene: MT-TL2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TL2.
Mode of inheritance for gene gene: MT-TL2 was set to MITOCHONDRIAL
Publications for gene: MT-TL2 were set to 8923013; 12398839; 19718780; 18977334; 21819490; 15649400; 15591266; 23847141; 20022607; 29052516
Phenotypes for gene: MT-TL2 were set to Mitochondrial disease (MONDO:0044970), MT-TL2-related
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark Marked gene: MT-TM as ready
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark Gene: mt-tm has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.39 Zornitza Stark Copied gene MT-TM from panel Mitochondrial disease
Rhabdomyolysis and Metabolic Myopathy v1.39 MT-TM Zornitza Stark gene: MT-TM was added
gene: MT-TM was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert Review Green,Expert list
mtDNA tags were added to gene: MT-TM.
Mode of inheritance for gene gene: MT-TM was set to MITOCHONDRIAL
Publications for gene: MT-TM were set to 9633749; 24711008; 25468263; 30739820; 11335700; 31488384; 31022467; 29174468
Phenotypes for gene: MT-TM were set to mitochondrial disease (MONDO:0044970), MT-TM-related
Mendeliome v1.4682 SLC26A5 Lucy Spencer reviewed gene: SLC26A5: Rating: AMBER; Mode of pathogenicity: None; Publications: 38431907, 38843436; Phenotypes: Deafness, autosomal recessive 61, MIM# 613865; Mode of inheritance: None
Mendeliome v1.4682 SLC19A1 Lucy Spencer Phenotypes for gene: SLC19A1 were changed from Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131 to Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131; myelomeningocele MONDO:0019773, SLC19A1-related
Mendeliome v1.4681 SLC19A1 Lucy Spencer reviewed gene: SLC19A1: Rating: RED; Mode of pathogenicity: None; Publications: 28948692; Phenotypes: myelomeningocele MONDO:0019773. SLC19A1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4681 WWP1 Sarah Milton gene: WWP1 was added
gene: WWP1 was added to Mendeliome. Sources: 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
Review for gene: WWP1 was set to RED
Added comment: WWP1 encodes a E3 ubiquitin ligase involved in protein trafficking.

PMID: 32699206 describes 10 individuals with autism found to have missense or splice variants in WWP1 with an autism phenotype. Variants were all found to be inherited apart from 2 in which inheritance was unknown. Phenotypes of parents were not included in the publication. Authors propose variants in this gene are more common in neurodevelopmental cohorts than control populations.
All variants apart from 1 detected in affected individuals were present in gnomad v4, with allele frequencies ranging from 4 heterozygotes to 4000 heterozygotes.

PMID: 41786693 describes another affected individual with development epileptic encephalopathy and regression with a de novo missense in WWP1. This variant was present in 4 heterozygotes in gnomad v4.
Extensive functional studies were performed in this paper in mice and cell lines showing gain of function variants in WWP1 in mice embryos resulted in abnormal neuronal migration and increased neuronal apoptosis.

Further studies are needed to demonstrate a Mendelian gene disease association.
Sources: Literature
Early-onset Dementia v1.58 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Ectodermal Dysplasia v0.110 RARG Zornitza Stark Marked gene: RARG as ready
Ectodermal Dysplasia v0.110 RARG Zornitza Stark Gene: rarg has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.110 Zornitza Stark Copied gene RARG from panel Mendeliome
Ectodermal Dysplasia v0.110 RARG Zornitza Stark gene: RARG was added
gene: RARG was added to Ectodermal Dysplasia. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RARG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RARG were set to 41830175
Phenotypes for gene: RARG were set to Ectodermal dysplasia syndrome, MONDO:0019287, RARG-related
Early-onset Dementia v1.57 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4680 RARG Zornitza Stark Marked gene: RARG as ready
Mendeliome v1.4680 RARG Zornitza Stark Gene: rarg has been classified as Red List (Low Evidence).
Mendeliome v1.4680 RARG Zornitza Stark changed review comment from: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features; the variant segregates in an autosomal‑dominant pattern and functional assays demonstrate dominant‑negative loss‑of‑function, but evidence is limited to one family.
Sources: Literature; to: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features. The truncating variant does not destabilise the transcript or protein produced from this allele but instead predicts the loss of half of helix 12 of RARγ, leading to reduced responsiveness of the receptor to all-trans retinoic acid via a dominant negative mechanism. Mice heterozygous for the variant demonstrated upregulation of cytokeratin-10 in the bladder and ureteric epithelium consistent with keratinising squamous metaplasia of the urothelium.
Sources: Literature
Mendeliome v1.4680 SIPA1L3 Lucy Spencer reviewed gene: SIPA1L3: Rating: AMBER; Mode of pathogenicity: None; Publications: 34603379; Phenotypes: Cataract 45 MIM#616851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4680 RARG Zornitza Stark gene: RARG was added
gene: RARG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RARG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RARG were set to 41830175
Phenotypes for gene: RARG were set to Ectodermal dysplasia syndrome, MONDO:0019287, RARG-related
Review for gene: RARG was set to RED
Added comment: PMID 41830175 reports four affected members from a single family with a heterozygous truncating RARG variant (c.1237C>T, p.Arg413*) causing childhood‑onset urothelial keratinising squamous metaplasia (KDSM) and associated ectodermal features; the variant segregates in an autosomal‑dominant pattern and functional assays demonstrate dominant‑negative loss‑of‑function, but evidence is limited to one family.
Sources: Literature
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark Marked gene: NEU4 as ready
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark Gene: neu4 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.349 Zornitza Stark Copied gene NEU4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.349 NEU4 Zornitza Stark gene: NEU4 was added
gene: NEU4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NEU4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU4 were set to 41833579
Phenotypes for gene: NEU4 were set to Hearing loss disorder, MONDO:0005365, NEU4-related
Motor Neurone Disease v1.48 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4679 NEU4 Zornitza Stark Marked gene: NEU4 as ready
Mendeliome v1.4679 NEU4 Zornitza Stark Gene: neu4 has been classified as Red List (Low Evidence).
Mendeliome v1.4679 NEU4 Zornitza Stark gene: NEU4 was added
gene: NEU4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEU4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU4 were set to 41833579
Phenotypes for gene: NEU4 were set to Hearing loss disorder, MONDO:0005365, NEU4-related
Review for gene: NEU4 was set to RED
Added comment: NEU4 encodes neuraminidase‑14, a sialidase involved in neuraminic acid catabolism and neuronal development. PMID 41833579 reports 2 individuals from a single family with biallelic compound heterozygous missense variants presenting with congenital moderate sensorineural hearing loss. Functional assays demonstrated markedly reduced neuraminidase activity and Neu4‑/‑ mice displayed mild hearing loss, supporting pathogenicity.
Sources: Literature
Motor Neurone Disease v1.47 RBMX Lucy Spencer Publications for gene: RBMX were set to 39263607
Motor Neurone Disease v1.46 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Motor Neurone Disease v1.46 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related to Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4678 RPL9 Lucy Spencer Phenotypes for gene: RPL9 were changed from Diamond Blackfan anaemia to Diamond-Blackfan anaemia MONDO:0015253, RPL9-related
Mendeliome v1.4677 RPL9 Lucy Spencer Publications for gene: RPL9 were set to 29114930; 20116044; 31799629
Mendeliome v1.4676 RPL9 Lucy Spencer reviewed gene: RPL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 34094714, 31799629, 29114930; Phenotypes: Diamond-Blackfan anaemia MONDO:0015253, RPL9-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.45 Lucy Spencer Copied gene RBMX from panel Mendeliome
Motor Neurone Disease v1.45 RBMX Lucy Spencer gene: RBMX was added
gene: RBMX was added to Motor Neurone Disease. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: RBMX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Early-onset Dementia v1.56 Lucy Spencer Copied gene RBMX from panel Mendeliome
Early-onset Dementia v1.56 RBMX Lucy Spencer gene: RBMX was added
gene: RBMX was added to Early-onset Dementia. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: RBMX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RBMX were set to 25256757; 34260915; 37277488; 39263607
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4676 RBMX Lucy Spencer Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555; Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related
Mendeliome v1.4675 RBMX Lucy Spencer Publications for gene: RBMX were set to 25256757; 34260915; 37277488
Mendeliome v1.4674 RBMX Lucy Spencer reviewed gene: RBMX: Rating: AMBER; Mode of pathogenicity: None; Publications: 39263607; Phenotypes: Amyotrophic lateral sclerosis MONDO:0004976, RBMX-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Lysosomal Storage Disorder v1.31 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Lysosomal Storage Disorder v1.31 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.60 AP5B1 Zornitza Stark Publications for gene: AP5B1 were set to 40081374
Macular Dystrophy/Stargardt Disease v0.59 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.59 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.58 Zornitza Stark Added reviews for gene AP5B1 from panel Mendeliome
Lysosomal Storage Disorder v1.30 Zornitza Stark Added reviews for gene AP5B1 from panel Mendeliome
Mendeliome v1.4674 AP5B1 Zornitza Stark commented on gene: AP5B1: Two more families reported.
Mendeliome v1.4674 AP5B1 Zornitza Stark Publications for gene: AP5B1 were set to 40081374
Mendeliome v1.4673 AP5B1 Zornitza Stark Classified gene: AP5B1 as Green List (high evidence)
Mendeliome v1.4673 AP5B1 Zornitza Stark Gene: ap5b1 has been classified as Green List (High Evidence).
Mendeliome v1.4672 AP5B1 Zornitza Stark reviewed gene: AP5B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41830174; Phenotypes: Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark Marked gene: ASAH2 as ready
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark Gene: asah2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.729 Zornitza Stark Copied gene ASAH2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.729 ASAH2 Zornitza Stark gene: ASAH2 was added
gene: ASAH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ASAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASAH2 were set to 41808410
Phenotypes for gene: ASAH2 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4672 ASAH2 Zornitza Stark Marked gene: ASAH2 as ready
Mendeliome v1.4672 ASAH2 Zornitza Stark Gene: asah2 has been classified as Red List (Low Evidence).
Mendeliome v1.4672 ASAH2 Zornitza Stark gene: ASAH2 was added
gene: ASAH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASAH2 were set to 41808410
Phenotypes for gene: ASAH2 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: ASAH2 was set to RED
Added comment: PMID 41808410 reports a single individual with biallelic loss-of-function (hypomorphic) missense variants presenting with a childhood-onset neurodevelopmental disorder characterized by cognitive impairment, neuropathy, ophthalmoplegia, and progressive cerebellar and extraocular muscle atrophy. Drosophila functional assays demonstrate reduced ASAH2 transcript and protein levels and neuromotor deficits, supporting loss-of-function.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark Marked gene: HIPK4 as ready
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.137 Zornitza Stark Copied gene HIPK4 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.137 HIPK4 Zornitza Stark gene: HIPK4 was added
gene: HIPK4 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: HIPK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIPK4 were set to 10.64898/2026.03.04.26346694; 35931115
Phenotypes for gene: HIPK4 were set to Infertility disorder, MONDO:0005047, HIPK4-related
Mendeliome v1.4671 HIPK4 Zornitza Stark Marked gene: HIPK4 as ready
Mendeliome v1.4671 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Mendeliome v1.4671 HIPK4 Zornitza Stark Classified gene: HIPK4 as Green List (high evidence)
Mendeliome v1.4671 HIPK4 Zornitza Stark Gene: hipk4 has been classified as Green List (High Evidence).
Mendeliome v1.4670 HIPK4 Zornitza Stark gene: HIPK4 was added
gene: HIPK4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIPK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIPK4 were set to 10.64898/2026.03.04.26346694; 35931115
Phenotypes for gene: HIPK4 were set to Infertility disorder, MONDO:0005047, HIPK4-related
Review for gene: HIPK4 was set to GREEN
Added comment: PMID 35931115 reports 10 individuals from 10 unrelated families with heterozygous loss‑of‑function HIPK4 variants presenting with nonobstructive azoospermia; functional assays demonstrate reduced protein for a truncating variant and Hipk4 knockout mice are sterile, supporting a monoallelic loss‑of‑function disease mechanism.
Sources: Literature
Mendeliome v1.4669 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.148 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.147 OCA2 Zornitza Stark edited their review of gene: OCA2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4668 IGFBP7 Sangavi Sivagnanasundram reviewed gene: IGFBP7: Rating: AMBER; Mode of pathogenicity: None; Publications: 35299703, 35464689; Phenotypes: familial retinal arterial macroaneurysm, MONDO:0013640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v1.18 PI4KA Eleanor Ludington gene: PI4KA was added
gene: PI4KA was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to PMID: 25855803
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Review for gene: PI4KA was set to AMBER
Added comment: 3 individuals from the same family described in PMID: 25855803 with biallelic PI4KA variants (nonsense variant and missense variant) presenting with arthrogryposis, polymicrogyria and cerebellar hypoplasia.
Sources: Literature
Mendeliome v1.4668 HAND1 Sangavi Sivagnanasundram changed review comment from: Additional reports of >5 unrelated probands with reported heterozygous variants in HAND1 (missense, promotor and 5'UTR variants)
Affected individuals presented with congenital heart disease, including septal defects, conotruncal malformations, tetralogy of Fallot, double outlet right ventricle, ventricular septal defect) of pediatric onset.

PMID:39107573 - Dual‑luciferase reporter assays for coding variants and luciferase/EMSA assays for promoter variants demonstrate loss‑of‑function of HAND1.; to: Additional reports of >5 unrelated probands with reported heterozygous variants in HAND1 (missense, promotor and 5'UTR variants)
Affected individuals presented with congenital heart disease, including septal defects, conotruncal malformations, tetralogy of Fallot, double outlet right ventricle, ventricular septal defect) of pediatric onset.

PMID:39107573 - Dual‑luciferase reporter assays for coding variants and luciferase/EMSA assays for promoter variants demonstrate loss‑of‑function of HAND1.

Classified as MODERATE by ClinGen Congenital Heart Disease GCEP on 04/04/2023 - https://search.clinicalgenome.org/CCID:005032
Congenital Heart Defect v0.534 Sangavi Sivagnanasundram Added reviews for gene HAND1 from panel Mendeliome
Mendeliome v1.4668 HAND1 Sangavi Sivagnanasundram 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, imprinted status unknown
Intellectual disability syndromic and non-syndromic v1.728 Sangavi Sivagnanasundram Added reviews for gene GTF2E2 from panel Mendeliome
Hair disorders v0.84 Sangavi Sivagnanasundram Added reviews for gene GTF2E2 from panel Mendeliome
Mendeliome v1.4668 GTF2E2 Sangavi Sivagnanasundram reviewed gene: GTF2E2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37793898, 31064989, 28973399; Phenotypes: trichothiodystrophy 6, nonphotosensitive, MONDO:0014841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v2.51 Sangavi Sivagnanasundram Added reviews for gene UQCRC1 from panel Incidentalome
Incidentalome v0.433 UQCRC1 Sangavi Sivagnanasundram reviewed gene: UQCRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41783485, 39752790, 33141179, 33070102, 30788857; Phenotypes: Parkinsonism with polyneuropathy, MONDO:0036193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.427 Sangavi Sivagnanasundram Added reviews for gene GNPNAT1 from panel Mendeliome
Mendeliome v1.4668 GNPNAT1 Sangavi Sivagnanasundram reviewed gene: GNPNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39945447, 36097642; Phenotypes: osteochondrodysplasia, MONDO:0005516; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.75 Sangavi Sivagnanasundram Added reviews for gene GAS2L2 from panel Mendeliome
Mendeliome v1.4668 GAS2L2 Sangavi Sivagnanasundram reviewed gene: GAS2L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36104176; Phenotypes: ciliary dyskinesia, primary, 41, MONDO:0032757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.727 ABCB7 Lucy Spencer Classified gene: ABCB7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.727 ABCB7 Lucy Spencer Gene: abcb7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.726 ABCB7 Lucy Spencer gene: ABCB7 was added
gene: ABCB7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABCB7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCB7 were set to 11050011; 26242992
Phenotypes for gene: ABCB7 were set to Anaemia, sideroblastic, with ataxia, MIM# 301310
Review for gene: ABCB7 was set to AMBER
Added comment: Some limited reports of developmental delay/ID in the literature and mentioned in the ClinGen review
Sources: Literature
Renal Tubulopathies and related disorders v1.26 Sangavi Sivagnanasundram Added reviews for gene FXYD2 from panel Mendeliome
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram changed review comment from: Classified as MODERATE by ClinGen Tubulopathy VCEP 29/06/2023 - https://search.clinicalgenome.org/CCID:004896 - this is based of the reports of a singular variant in multiple families

PMID: 40428357 - reports a Polish family (2 sibs and mother) presenting with hypercalciuria, glucosuria and mild proteinuria. The mother presented with a milder phenotype compared to the children.
c.80G>A, p.(Arg27His) - Variant is present in gnomAD v4.1 with global FAF - 0.00098% (23 hets globally)

Upgrade to green given a second variant that is shown to segregate in affected members of the family (siblings and mother); to: Classified as MODERATE by ClinGen Tubulopathy VCEP 29/06/2023 - https://search.clinicalgenome.org/CCID:004896 - this is based of the reports of a singular variant in multiple families

PMID: 40428357 - reports a Polish family (2 sibs and mother) presenting with hypercalciuria, glucosuria and mild proteinuria. The mother presented with a milder phenotype compared to the children.
c.80G>A, p.(Arg27His) - Variant is present in gnomAD v4.1 with global FAF - 0.00098% (23 hets globally)

Remain as Amber given that only two variants have been reported in affected individuals and no supportive functional evidence has been reported as of yet.
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram edited their review of gene: FXYD2: Changed rating: AMBER
Mendeliome v1.4668 FXYD2 Sangavi Sivagnanasundram reviewed gene: FXYD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 40428357; Phenotypes: Renal hypomagnesemia 2, MONDO:0007937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Incidentalome v0.433 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Differences of Sex Development v1.45 MARS2 Zornitza Stark Classified gene: MARS2 as Red List (low evidence)
Differences of Sex Development v1.45 MARS2 Zornitza Stark Gene: mars2 has been classified as Red List (Low Evidence).
Red cell disorders v1.52 BPGM Bryony Thompson Publications for gene: BPGM were set to 1421379; 27651169; 25015942
Red cell disorders v1.51 BPGM Bryony Thompson Mode of inheritance for gene: BPGM was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Red cell disorders v1.50 BPGM Bryony Thompson Classified gene: BPGM as Green List (high evidence)
Red cell disorders v1.50 BPGM Bryony Thompson Gene: bpgm has been classified as Green List (High Evidence).
Red cell disorders v1.49 Bryony Thompson Added reviews for gene BPGM from panel Mendeliome
Mendeliome v1.4668 BPGM Bryony Thompson Publications for gene: BPGM were set to 1421379; 27651169; 25015942
Mendeliome v1.4667 BPGM Bryony Thompson Mode of inheritance for gene: BPGM was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.4666 BPGM Bryony Thompson Classified gene: BPGM as Green List (high evidence)
Mendeliome v1.4666 BPGM Bryony Thompson Gene: bpgm has been classified as Green List (High Evidence).
Mendeliome v1.4665 BPGM Bryony Thompson reviewed gene: BPGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36177683, 35142155, 33216349, 29790589, 27651169; Phenotypes: hemolytic anemia due to diphosphoglycerate mutase deficiency, MONDO:0009113; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Skeletal dysplasia v0.426 Bryony Thompson Added reviews for gene BNIP1 from panel Mendeliome
Mendeliome v1.4665 BNIP1 Bryony Thompson edited their review of gene: BNIP1: Added comment: PMIDs 35266227 and 39706863 report a total of 3 unrelated families with homozygous hypomorphic BNIP1 variants with childhood‑onset spondylo‑epiphyseal dysplasia. Affected individuals present with disproportionate short stature, vertebral and epiphyseal abnormalities. Functional studies in the two families from PMID 35266227 demonstrate abnormal splicing, ~50% reduction of BNIP1 protein, accumulation of LC3B‑positive autophagosomes and impaired autophagic flux, supporting a loss‑of‑function mechanism. The third family adds an independent case without functional validation. No contradictory evidence is reported.; Changed publications: 39706863, 35266227; Changed phenotypes: Syndromic disease, MONDO:0002254
Pulmonary Arterial Hypertension v1.56 Bryony Thompson Added reviews for gene BMP10 from panel Mendeliome
Mendeliome v1.4665 BMP10 Bryony Thompson reviewed gene: BMP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 38514094, 38322548, 36673052, 35737725, 33187088, 31243186, 30872557, 30578383; Phenotypes: pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4665 CLN3 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association with ceroid lipofuscinosis.
Mendeliome v1.4665 CLN3 Zornitza Stark edited their review of gene: CLN3: Added comment: At least 20 families reported with isolated RP.; Changed publications: 7553855, 28542676, 33507216; Changed phenotypes: Ceroid lipofuscinosis, neuronal, 3, MIM# 204200, MONDO:0008767, Retinitis pigmentosa 101, MIM# 621548
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.245 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from Retinitis pigmentosa; Juvenile neuronal ceroid lipofuscinosis to Retinitis pigmentosa 101, MIM# 621548
Retinitis pigmentosa v0.244 CLN3 Zornitza Stark Publications for gene: CLN3 were set to
Retinitis pigmentosa v0.243 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 101, MIM# 621548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4665 DIO1 Bryony Thompson Publications for gene: DIO1 were set to
Deafness_IsolatedAndComplex v1.348 DIAPH3 Bryony Thompson Classified gene: DIAPH3 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.348 DIAPH3 Bryony Thompson Gene: diaph3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.347 DIAPH3 Bryony Thompson Publications for gene: DIAPH3 were set to 23441200; 20624953; 27658576; 38860500; 39767564
Deafness_IsolatedAndComplex v1.346 Bryony Thompson Added reviews for gene DIAPH3 from panel Mendeliome
Mendeliome v1.4664 DIAPH3 Bryony Thompson Classified gene: DIAPH3 as Green List (high evidence)
Mendeliome v1.4664 DIAPH3 Bryony Thompson Gene: diaph3 has been classified as Green List (High Evidence).
Mendeliome v1.4663 DIAPH3 Bryony Thompson reviewed gene: DIAPH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 41511813, 40040362, 38860500, 39767564, 20624953; Phenotypes: autosomal dominant auditory neuropathy 1, MONDO:0012196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ocular and Oculocutaneous Albinism v1.16 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ocular and Oculocutaneous Albinism v1.15 OCA2 Zornitza Stark edited their review of gene: OCA2: Added comment: OCA2 is now supported by 53 unrelated families (63 patients) across five studies. All families show autosomal recessive inheritance.; Changed publications: 32741191, 20301410, 38030918, 41807736, 31141302, 37650133, 41292147
Mendeliome v1.4663 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous to Albinism, oculocutaneous, type II, MIM# 203200
Mendeliome v1.4662 OCA2 Zornitza Stark Publications for gene: OCA2 were set to 32741191; 24518832; 20301410
Mendeliome v1.4661 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4660 OCA2 Zornitza Stark reviewed gene: OCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38030918, 41807736, 31141302, 37650133, 41292147; Phenotypes: Albinism, oculocutaneous, type II, MIM# 203200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4660 CTGF Bryony Thompson Mode of inheritance for gene: CTGF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4659 NLRP5 Zornitza Stark Phenotypes for gene: NLRP5 were changed from Early embryonic arrest; Multi locus imprinting disturbance in offspring to Early embryonic arrest; Multi locus imprinting disturbance in offspring; Oocyte/zygote/embryo maturation arrest 19, MIM# 620333
Mendeliome v1.4658 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238; 26323243; 34440388
Mendeliome v1.4657 NLRP5 Zornitza Stark edited their review of gene: NLRP5: Added comment: PMID 39887367 reports 7 unrelated families with biallelic NLRP5 variants causing early embryonic arrest and female infertility; Changed publications: 32222962, 31829238, 30877238, 26323243, 34440388, 39887367; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring, Oocyte/zygote/embryo maturation arrest 19, MIM# 620333
Infertility and Recurrent Pregnancy Loss v1.136 NLRP5 Zornitza Stark Publications for gene: NLRP5 were set to 30877238; 32222962; 35091966; 35946397; 33583041
Infertility and Recurrent Pregnancy Loss v1.135 NLRP5 Zornitza Stark reviewed gene: NLRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 39887367; Phenotypes: Oocyte/zygote/embryo maturation arrest 19, MIM# 620333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.554 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Atrial septal defect 3 (MIM#614089) to Atrial septal defect 3 (MIM#614089); MYH-6 related congenital heart defects MONDO:0800442
Fetal anomalies v1.553 MYH6 Zornitza Stark Publications for gene: MYH6 were set to 20656787; 29969989; 15735645
Fetal anomalies v1.552 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.551 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28991257; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4657 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Atrial septal defect 3 MIM#614089; Congenital heart disease; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090 to Atrial septal defect 3 MIM#614089; MYH-6 related congenital heart defects MONDO:0800442; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090
Mendeliome v1.4656 MYH6 Zornitza Stark Publications for gene: MYH6 were set to 32656206; 31638415; 29969989; 29536580; 29332214; 30681346
Mendeliome v1.4655 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4654 MYH6 Zornitza Stark changed review comment from: Please note the association with HCM has been rated as LIMITED by ClinGen.

There is a broader reported association with congenital heart disease beyond ASD.; to: Please note the association with HCM has been rated as LIMITED by ClinGen. The association with HCM is DISPUTED.

There is a broader reported association with congenital heart disease beyond ASD.
Mendeliome v1.4654 MYH6 Zornitza Stark edited their review of gene: MYH6: Added comment: PMID 28991257 reports 7 unrelated families with biallelic MYH6 variants (loss‑of‑function and missense alleles) causing Shone complex—a left‑ventricular outflow tract obstruction syndrome with mitral and aortic valve disease.; Changed publications: 32656206, 31638415, 29969989, 29536580, 29332214, 30681346, 28991257; Changed phenotypes: Atrial septal defect 3 MIM#614089, MYH-6 related congenital heart defects MONDO:0800442, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Marked gene: MYH6 as ready
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Gene: myh6 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.533 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Congenital Heart Defect v0.532 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.531 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28991257; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.551 KIF22 Zornitza Stark Publications for gene: KIF22 were set to 25256152; 22152677; 22152678
Fetal anomalies v1.550 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.549 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2, MIM# 603546; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Marked gene: KIF22 as ready
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Gene: kif22 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.425 KIF22 Zornitza Stark Phenotypes for gene: KIF22 were changed from Spondyloepimetaphyseal dysplasia with joint laxity, type 2 603546 to Spondyloepimetaphyseal dysplasia with joint laxity, type 2, MIM# 603546
Skeletal dysplasia v0.424 KIF22 Zornitza Stark Publications for gene: KIF22 were set to
Skeletal dysplasia v0.423 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.422 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.422 Zornitza Stark Added reviews for gene KIF22 from panel Mendeliome
Fetal anomalies v1.549 Zornitza Stark Added reviews for gene KIF22 from panel Mendeliome
Mendeliome v1.4654 KIF22 Zornitza Stark Publications for gene: KIF22 were set to 22152677; 22152678; 25256152
Mendeliome v1.4653 KIF22 Zornitza Stark Mode of inheritance for gene: KIF22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4652 KIF22 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported with mono allelic disease.
Mendeliome v1.4652 KIF22 Zornitza Stark edited their review of gene: KIF22: Added comment: PMID 38477767 reports six individuals from six unrelated families (three with a homozygous c.146G>A p.Arg49Gln recessive variant and three with heterozygous c.443C>T p.Pro148Leu or c.446G>A p.Arg149Gln dominant variants) presenting with spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto‑SEMDJL). All patients display short stature, generalized joint laxity, multiple dislocations, scoliosis, and characteristic radiographic findings.

Evidence for recessive disease is limited to the one variant, albeit in three families (?founder).; Changed publications: 25256152, 38477767; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.135 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 33036707; 38643161
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.408 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 8849725; 33036707
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.407 Zornitza Stark Added reviews for gene GDF9 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.134 Zornitza Stark Added reviews for gene GDF9 from panel Mendeliome
Mendeliome v1.4652 GDF9 Zornitza Stark Publications for gene: GDF9 were set to 29044499; 8849725; 33036707
Mendeliome v1.4651 GDF9 Zornitza Stark edited their review of gene: GDF9: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4651 GDF9 Zornitza Stark reviewed gene: GDF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 41783724, 38942181, 38672141, 38649916, 38643161, 35013061, 34095689, 33797006, 33538981, 33095795, 29044499, 27603904; Phenotypes: Premature ovarian failure 14, OMIM# 618014; Mode of inheritance: None
Mendeliome v1.4651 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from autosomal recessive distal renal tubular acidosis MONDO:0018440 to autosomal recessive distal renal tubular acidosis MONDO:0018440; Hearing loss disorder, MONDO:0005365, FOXI1-related
Mendeliome v1.4650 FOXI1 Zornitza Stark Publications for gene: FOXI1 were set to 9843211; 12642503; 29242249; 17503324; 30268946; 27997596; 22285650; 23965030; 24860705; 32447495; 19204907
Mendeliome v1.4649 FOXI1 Zornitza Stark Mode of inheritance for gene: FOXI1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4648 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41833579, 27997596; Phenotypes: Hearing loss disorder, MONDO:0005365, FOXI1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.345 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from autosomal recessive distal renal tubular acidosis MONDO:0018440 to autosomal recessive distal renal tubular acidosis MONDO:0018440; Hearing loss disorder, MONDO:0005365, FOXI1-related
Deafness_IsolatedAndComplex v1.344 FOXI1 Zornitza Stark Publications for gene: FOXI1 were set to 9843211; 12642503; 29242249; 17503324; 30268946; 27997596; 22285650; 23965030; 24860705; 32447495; 19204907
Deafness_IsolatedAndComplex v1.343 FOXI1 Zornitza Stark Mode of inheritance for gene: FOXI1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.342 FOXI1 Zornitza Stark edited their review of gene: FOXI1: Added comment: PMID 41833579: reports 2 individuals from 2 unrelated families (F814 and F824) with a de novo heterozygous in‑frame deletion c.479_481del (p.Asn161del) presenting with Mondini malformation, enlarged vestibular aqueduct, and severe to profound sensorineural hearing loss. The variant is absent from gnomAD and other databases. Functional evidence includes a Foxi1 N155del/+ knock‑in mouse model that recapitulates cochlear dysplasia, EVA and elevated ABR thresholds, and luciferase reporter assays showing a dominant‑negative reduction of SLC26A4 promoter activity.

PMID 27997596 reports 2 unrelated individuals with heterozygous FOXI1 missense variants (c.519C>A de novo, c.716C>T) presenting with childhood‑onset sensorineural hearing loss and enlarged vestibular aqueduct. c.519C>A lies in the conserved forkhead DNA‑binding domain.; Changed rating: GREEN; Changed publications: 41833579, 27997596; Changed phenotypes: Hearing loss disorder, MONDO:0005365, FOXI1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.217 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes
Monogenic Diabetes v0.216 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Monogenic Diabetes v0.215 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Monogenic Diabetes v0.215 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Monogenic Diabetes v0.214 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Changed publications: 41808409
Monogenic Diabetes v0.214 RNU6ATAC Zornitza Stark changed review comment from: PMID 40975062 reports 1 individual from with biallelic RNU6ATAC variants causing childhood‑onset growth restriction, microcephaly, epilepsy, intellectual disability and ataxia. PMID 41808409 reports 3 unrelated families (3 individuals) with biallelic loss‑of‑function RNU6ATAC variants presenting with short stature, neurodevelopmental delay, epilepsy, immunodeficiency, skeletal dysplasia and other multisystem features; RNA‑seq shows marked excess of minor intron retention, confirming spliceosome dysfunction.

However, note overlap in authors between the two papers ?double-counting.

PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.

Genotype-phenotype correlation unclear at this stage but note that of the three individuals reported in 41808409, one did not have ID/neurological features but all had immunological involvement.; to: PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.
Intellectual disability syndromic and non-syndromic v1.725 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related; neonatal diabetes
Intellectual disability syndromic and non-syndromic v1.724 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Intellectual disability syndromic and non-syndromic v1.723 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.723 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Genetic Epilepsy v1.398 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Genetic Epilepsy v1.397 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Genetic Epilepsy v1.396 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Genetic Epilepsy v1.396 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Monogenic Diabetes v0.214 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Genetic Epilepsy v1.395 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Genetic Epilepsy v1.395 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.722 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Genetic Epilepsy v1.394 Zornitza Stark Added reviews for gene RNU6ATAC from panel Mendeliome
Microcephaly v1.424 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Microcephaly v1.423 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Microcephaly v1.422 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Microcephaly v1.422 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Microcephaly v1.421 RNU6ATAC Zornitza Stark edited their review of gene: RNU6ATAC: Added comment: PMID 40975062 reports 1 individual from with biallelic RNU6ATAC variants causing childhood‑onset growth restriction, microcephaly, epilepsy, intellectual disability and ataxia. PMID 41808409 reports 3 unrelated families (3 individuals) with biallelic loss‑of‑function RNU6ATAC variants presenting with short stature, neurodevelopmental delay, epilepsy, immunodeficiency, skeletal dysplasia and other multisystem features; RNA‑seq shows marked excess of minor intron retention, confirming spliceosome dysfunction.

However, note overlap in authors between the two papers ?double-counting.

PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.

Genotype-phenotype correlation unclear at this stage but note that of the three individuals reported in 41808409, one did not have ID/neurological features but all had immunological involvement.; Changed rating: GREEN; Changed publications: 41808409, 40975062, 41864208; Changed phenotypes: Syndromic disease, MONDO:0002254, RNU6ATAC-related
Disorders of immune dysregulation v1.40 Zornitza Stark Copied gene RNU6ATAC from panel Mendeliome
Disorders of immune dysregulation v1.40 RNU6ATAC Zornitza Stark gene: RNU6ATAC was added
gene: RNU6ATAC was added to Disorders of immune dysregulation. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: RNU6ATAC.
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 41808409; 40975062; 41864208
Phenotypes for gene: RNU6ATAC were set to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Mendeliome v1.4648 RNU6ATAC Zornitza Stark Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Mendeliome v1.4647 RNU6ATAC Zornitza Stark Publications for gene: RNU6ATAC were set to 40975062
Mendeliome v1.4646 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Green List (high evidence)
Mendeliome v1.4646 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Green List (High Evidence).
Mendeliome v1.4645 RNU6ATAC Zornitza Stark reviewed gene: RNU6ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41808409, 40975062, 41864208; Phenotypes: Syndromic disease, MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4645 Bryony Thompson Added reviews for gene ERG from panel Bone Marrow Failure
Leukodystrophy v0.393 Rylee Peters Added reviews for gene PLEKHG2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.721 Rylee Peters Added reviews for gene PLEKHG2 from panel Mendeliome
Mendeliome v1.4644 PLEKHG2 Rylee Peters Publications for gene: PLEKHG2 were set to 26573021
Mendeliome v1.4643 PLEKHG2 Rylee Peters reviewed gene: PLEKHG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 40594583; Phenotypes: Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4643 OXA1L Rylee Peters 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
Cone-rod Dystrophy v0.63 OPN1MW Rylee Peters Classified gene: OPN1MW as Green List (high evidence)
Cone-rod Dystrophy v0.63 OPN1MW Rylee Peters Gene: opn1mw has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.62 Rylee Peters Added reviews for gene OPN1MW from panel Mendeliome
Mendeliome v1.4643 OPN1MW Rylee Peters Classified gene: OPN1MW as Green List (high evidence)
Mendeliome v1.4643 OPN1MW Rylee Peters Gene: opn1mw has been classified as Green List (High Evidence).
Mendeliome v1.4642 OPN1MW Rylee Peters changed review comment from: Green rating for Colorblindness, deutan, MIM#303800

OPN1MW is Definitively associated with OPN1MW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

OPN1LW is definitively associated with OPN1LW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

"Per criteria outlined by the ClinGen Lumping & Splitting Working Group, diverse cases were compared and found to share an X-linked mode of inheritance and a degree of overlap in their phenotypes, but to differ in the mechanism of pathogenicity underlying deutan color blindness (monogenic OPN1MW loss-of-function) versus blue cone monochromacy (digenic OPN1MW and OPN1LW loss-of-function)."; to: Green rating for Colorblindness, deutan, MIM#303800

OPN1MW is Definitively associated with OPN1MW-related cone dysfunction - classification was approved by the ClinGen Retina Gene Curation Expert Panel on September 4th, 2025.

"Per criteria outlined by the ClinGen Lumping & Splitting Working Group, diverse cases were compared and found to share an X-linked mode of inheritance and a degree of overlap in their phenotypes, but to differ in the mechanism of pathogenicity underlying deutan color blindness (monogenic OPN1MW loss-of-function) versus blue cone monochromacy (digenic OPN1MW and OPN1LW loss-of-function)."
Mendeliome v1.4642 OPN1MW Rylee Peters reviewed gene: OPN1MW: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorblindness, deutan, MIM#303800; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cone-rod Dystrophy v0.61 OPN1LW Rylee Peters Classified gene: OPN1LW as Green List (high evidence)
Cone-rod Dystrophy v0.61 OPN1LW Rylee Peters Gene: opn1lw has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.60 Rylee Peters Added reviews for gene OPN1LW from panel Mendeliome
Mendeliome v1.4642 OPN1LW Rylee Peters Classified gene: OPN1LW as Green List (high evidence)
Mendeliome v1.4642 OPN1LW Rylee Peters Gene: opn1lw has been classified as Green List (High Evidence).
Mendeliome v1.4641 OPN1LW Rylee Peters reviewed gene: OPN1LW: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorblindness, protan, MIM#303900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Gastrointestinal neuromuscular disease v1.26 Rylee Peters Added reviews for gene NRG1 from panel Mendeliome
Mendeliome v1.4641 NRG1 Rylee Peters Mode of inheritance for gene: NRG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4640 NRG1 Rylee Peters Phenotypes for gene: NRG1 were changed from Hirschsprung disease, MONDO:0018309; Peripheral neuropathy MONDO:0005244 to Hirschsprung disease, susceptibility (MONDO:0100179), NRG1-related; Peripheral neuropathy MONDO:0005244
Mendeliome v1.4639 NRG1 Rylee Peters Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Mendeliome v1.4638 NRG1 Rylee Peters reviewed gene: NRG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33421311, 31240788; Phenotypes: Hirschsprung disease, susceptibility (MONDO:0100179), NRG1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.393 Rylee Peters Added reviews for gene NECAP1 from panel Mendeliome
Mendeliome v1.4638 NECAP1 Rylee Peters reviewed gene: NECAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35638367; Phenotypes: Developmental and epileptic encephalopathy 21, MIM#615833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.548 Rylee Peters Added reviews for gene MMP15 from panel Mendeliome
Cholestasis v1.10 Rylee Peters Added reviews for gene MMP15 from panel Mendeliome
Mendeliome v1.4638 MMP15 Rylee Peters Publications for gene: MMP15 were set to 33875846
Mendeliome v1.4637 MMP15 Rylee Peters reviewed gene: MMP15: Rating: AMBER; Mode of pathogenicity: None; Publications: 36349822; Phenotypes: Progressive familial intrahepatic cholestasis, MONDO:0015762, MMP15-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4637 PADI6 Bryony Thompson Publications for gene: PADI6 were set to 29693651; 33583041; 329228291; 33221824; 27545678
Mendeliome v1.4636 NLRP5 Bryony Thompson Publications for gene: NLRP5 were set to 32232222962; 31829238; 30877238; 26323243; 34440388
Mendeliome v1.4635 AMELX Bryony Thompson Publications for gene: AMELX were set to 17189466; 22243263; 7599636; 23251683; 1483698 1916828; 9188994; 15111628; 11201048; 26502894; 7782077; 11922869; 28130977; 8406474; 11839357; 25117480; 19610109
Mendeliome v1.4634 ZBTB26 Chirag Patel Marked gene: ZBTB26 as ready
Mendeliome v1.4634 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Mendeliome v1.4634 Chirag Patel Copied gene ZBTB26 from panel Congenital hypothyroidism
Mendeliome v1.4634 ZBTB26 Chirag Patel gene: ZBTB26 was added
gene: ZBTB26 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZBTB26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB26 were set to 34946811
Phenotypes for gene: ZBTB26 were set to Congenital hypothyroidism MONDO:0018612
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Marked gene: ZBTB26 as ready
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Classified gene: ZBTB26 as Green List (high evidence)
Congenital hypothyroidism v0.117 ZBTB26 Chirag Patel Gene: zbtb26 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.116 ZBTB26 Chirag Patel gene: ZBTB26 was added
gene: ZBTB26 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: ZBTB26 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB26 were set to 34946811
Phenotypes for gene: ZBTB26 were set to Congenital hypothyroidism MONDO:0018612
Review for gene: ZBTB26 was set to GREEN
Added comment: PMID 34946811 reports 3 individuals from 3 unrelated families with heterozygous ZBTB26 variants (2 x missense and 1 x splice‑proximal) presenting with congenital primary hypothyroidism. De novo status confirmed for 1 patient but parental status unavailable for 2 patients. Xenopus loss‑of‑function studies recapitulated the phenotype and were rescued by wild‑type mRNA, supporting a loss‑of‑function mechanism.
Sources: Literature
Congenital hypothyroidism v0.115 UBR7 Chirag Patel Marked gene: UBR7 as ready
Congenital hypothyroidism v0.115 UBR7 Chirag Patel Gene: ubr7 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.115 Chirag Patel Copied gene UBR7 from panel Mendeliome
Congenital hypothyroidism v0.115 UBR7 Chirag Patel gene: UBR7 was added
gene: UBR7 was added to Congenital hypothyroidism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: UBR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBR7 were set to 33340455
Phenotypes for gene: UBR7 were set to Li-Campeau syndrome, MIM# 619189; Intellectual disability; epilepsy; hypothyroidism; congenital anomalies; dysmorphic features
Genetic Epilepsy v1.392 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339; 38705457
Genetic Epilepsy v1.391 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Marked gene: TANGO2 as ready
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Gene: tango2 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.114 TANGO2 Chirag Patel Publications for gene: TANGO2 were set to 26805782; 30245509
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel edited their review of gene: TANGO2: Added comment: hypothyroidism noted in 12/20 (PMID: 32929747) and 31/65 (PMID: 36473599) patients but unclear of age of onset.; Changed rating: AMBER; Changed publications: 36473599 32929747
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Classified gene: TANGO2 as Amber List (moderate evidence)
Congenital hypothyroidism v0.113 TANGO2 Chirag Patel Gene: tango2 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.112 TANGO2 Chirag Patel Classified gene: TANGO2 as Red List (low evidence)
Congenital hypothyroidism v0.112 TANGO2 Chirag Patel Gene: tango2 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.111 TANGO2 Chirag Patel reviewed gene: TANGO2: Rating: RED; Mode of pathogenicity: None; Publications: 36473599, 32929747; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.390 Rylee Peters Added reviews for gene MICAL1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Gene: dlx5 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Classified gene: DLX5 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.342 DLX5 Zornitza Stark Gene: dlx5 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.111 Chirag Patel Copied gene TANGO2 from panel Mendeliome
Congenital hypothyroidism v0.111 TANGO2 Chirag Patel gene: TANGO2 was added
gene: TANGO2 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 26805782; 30245509
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Deafness_IsolatedAndComplex v1.341 DLX5 Zornitza Stark gene: DLX5 was added
gene: DLX5 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: DLX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLX5 were set to 41760400; 22121204
Phenotypes for gene: DLX5 were set to Split-hand/foot malformation 1 with sensorineural hearing loss, MIM# 220600
Review for gene: DLX5 was set to AMBER
Added comment: Two families reported with bi-allelic variants and SHFM/SNHL.
Sources: Literature
Mendeliome v1.4633 MICAL1 Rylee Peters Publications for gene: MICAL1 were set to 29394500; 21638339
Mendeliome v1.4632 MICAL1 Rylee Peters reviewed gene: MICAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38705457, 29394500; Phenotypes: Epilepsy, MONDO:0005027, MICAL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Marked gene: SGPL1 as ready
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Gene: sgpl1 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.110 SGPL1 Chirag Patel Publications for gene: SGPL1 were set to 33074640
Fetal anomalies v1.547 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 22121204; 24496061; 25196357; 20534536; 12112878
Congenital hypothyroidism v0.109 SGPL1 Chirag Patel reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35904228, 35748945, 32322566, 28165343, 38204317; Phenotypes: Sphingosine phosphate lyase insufficiency syndrome (SPLIS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.546 DLX5 Zornitza Stark reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 41760400; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v0.85 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Hand and foot malformations v0.85 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Hand and foot malformations v0.85 DLX5 Zornitza Stark Publications for gene: DLX5 were set to
Hand and foot malformations v0.84 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 41760400
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.421 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 27085093
Skeletal dysplasia v0.420 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 41760400
Mendeliome v1.4632 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 22121204; 24496061; 25196357; 20534536; 12112878
Mendeliome v1.4631 DLX5 Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 22121204, 24496061, 25196357, 20534536, 12112878, 41760400
Congenital hypothyroidism v0.109 Chirag Patel Copied gene SGPL1 from panel Adrenal insufficiency
Congenital hypothyroidism v0.109 SGPL1 Chirag Patel gene: SGPL1 was added
gene: SGPL1 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 33074640
Phenotypes for gene: SGPL1 were set to RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel Marked gene: RNPC3 as ready
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.720 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Classified gene: RNPC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.719 RNPC3 Chirag Patel Gene: rnpc3 has been classified as Green List (High Evidence).
Mendeliome v1.4631 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Growth failure v1.101 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 32462814; 29866761; 24480542; 33650182
Mendeliome v1.4630 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Intellectual disability syndromic and non-syndromic v1.718 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Growth failure v1.100 Chirag Patel Added reviews for gene RNPC3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.108 Chirag Patel Copied gene RNPC3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.108 RNPC3 Chirag Patel gene: RNPC3 was added
gene: RNPC3 was added to Congenital hypothyroidism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182; 37463572; 35792517; 34906446
Phenotypes for gene: RNPC3 were set to Growth hormone deficiency; Intellectual disability
Pituitary hormone deficiency v0.199 RNPC3 Chirag Patel Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel reviewed gene: RNPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37463572, 35792517, 34906446; Phenotypes: Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel Deleted their review
Pituitary hormone deficiency v0.198 RNPC3 Chirag Patel reviewed gene: RNPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37463572, 35792517; Phenotypes: Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4629 KCNH5 Bryony Thompson Publications for gene: KCNH5 were set to https://www.medrxiv.org/content/10.1101/2022.04.26.22274147v1
Susceptibility to Viral Infections v1.10 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from Inborn error of immunity, MONDO:0003778, DOC2-related to Inborn error of immunity, MONDO:0003778, DOCK2-related
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark edited their review of gene: DOCK2: Changed phenotypes: Inborn error of immunity, MONDO:0003778, DOCK2-related
Mendeliome v1.4628 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels to Immunodeficiency 40 MIM# 616433; Inborn error of immunity, MONDO:0003778, DOCK2-related
Mendeliome v1.4627 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to 26083206; 29204803; 33928462; 30826364; 30838481; 11518968
Mendeliome v1.4626 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4625 DOCK2 Zornitza Stark changed review comment from: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).; to: Bi-allelic disease: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).
Mendeliome v1.4625 DOCK2 Zornitza Stark edited their review of gene: DOCK2: Added comment: PMID 41654261: Six individuals from three unrelated families, aged 3 months to 50 years, reported with one of three heterozygous variants in DOCK2 and severe infections with human papilloma virus, respiratory syncytial virus, or SARS-CoV-2. All variants reside within the DOCK2 domain that binds and stabilizes ELMO1. Each variant reduced DOCK2 protein expression, ELMO1 binding, and DOCK2 function, as shown by diminished Rac1 activation and selective defects in Toll-like receptor signaling. Weekly IFN-α therapy led to complete resolution of refractory warts in one patient, highlighting a potential therapeutic approach for DOCK2-associated immunodeficiency.

PMID 36836791: Patient with recurrent HLH. Heterozygous c.1334A>G (p.Asn445Ser) variant. Functional studies showing lower CD107a expression and diminished NK degranulation and cytotoxicity. ? partial dominant negative.; Changed publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968, 41654261, 36836791; Changed phenotypes: Immunodeficiency 40 MIM# 616433, Inborn error of immunity, MONDO:0003778, DOCK2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Classified gene: DOCK2 as Green List (high evidence)
Susceptibility to Viral Infections v1.9 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.99 PROKR2 Chirag Patel Deleted their comment
Pituitary hormone deficiency v0.198 PROKR2 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.107 POMC Chirag Patel Publications for gene: POMC were set to 33666293
Pituitary hormone deficiency v0.198 POMC Chirag Patel Publications for gene: POMC were set to 33666293
Pituitary hormone deficiency v0.197 POMC Chirag Patel Marked gene: POMC as ready
Pituitary hormone deficiency v0.197 POMC Chirag Patel Gene: pomc has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.197 POMC Chirag Patel reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 40513101, 34177811, 29858905; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.106 POMC Chirag Patel Marked gene: POMC as ready
Congenital hypothyroidism v0.106 POMC Chirag Patel Gene: pomc has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.106 POMC Chirag Patel reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 40513101, 34177811, 29858905; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.197 Chirag Patel Copied gene POMC from panel Mendeliome
Pituitary hormone deficiency v0.197 POMC Chirag Patel gene: POMC was added
gene: POMC was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POMC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMC were set to 33666293
Phenotypes for gene: POMC were set to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Congenital hypothyroidism v0.106 Chirag Patel Copied gene POMC from panel Mendeliome
Congenital hypothyroidism v0.106 POMC Chirag Patel gene: POMC was added
gene: POMC was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POMC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMC were set to 33666293
Phenotypes for gene: POMC were set to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Susceptibility to Viral Infections v1.8 DOCK2 Zornitza Stark gene: DOCK2 was added
gene: DOCK2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: DOCK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK2 were set to 41654261
Phenotypes for gene: DOCK2 were set to Inborn error of immunity, MONDO:0003778, DOC2-related
Review for gene: DOCK2 was set to GREEN
Added comment: Six individuals from three unrelated families, aged 3 months to 50 years, reported with one of three heterozygous variants in DOCK2 and severe infections with human papilloma virus, respiratory syncytial virus, or SARS-CoV-2. All variants reside within the DOCK2 domain that binds and stabilizes ELMO1. Each variant reduced DOCK2 protein expression, ELMO1 binding, and DOCK2 function, as shown by diminished Rac1 activation and selective defects in Toll-like receptor signaling. Weekly IFN-α therapy led to complete resolution of refractory warts in one patient, highlighting a potential therapeutic approach for DOCK2-associated immunodeficiency.
Sources: Literature
Skeletal dysplasia v0.420 POC1A Chirag Patel Marked gene: POC1A as ready
Skeletal dysplasia v0.420 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.420 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.419 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813; Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Skeletal dysplasia v0.419 POC1A Chirag Patel Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357; 39662966
Skeletal dysplasia v0.419 POC1A Chirag Patel Publications for gene: POC1A were set to 26374189; 26162852; 26336158
Skeletal dysplasia v0.418 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.717 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.716 POC1A Chirag Patel Publications for gene: POC1A were set to
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.715 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM#614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Classified gene: POC1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Hand and foot malformations v0.84 Sarah Milton Copied Region PITX1 upstream regulatory region from panel Mendeliome
Hand and foot malformations v0.84 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Hand and foot malformations. Sources: Literature
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
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Classified gene: POC1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.714 POC1A Chirag Patel Gene: poc1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.713 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4625 PITX1 upstream regulatory region Sarah Milton Region: PITX1 upstream regulatory region was added
Region: PITX1 upstream regulatory region was added to Mendeliome. Sources: Literature
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
Review for Region: PITX1 upstream regulatory region was set to GREEN
Added comment: PITX1 is a transcription factor expressed solely in the hindlimb during limb development where it ensures proper outgrowth and patterning of this tissue.

Over 25 individuals have been reported in the literature with deletions upstream of PITX1 presenting with Liebenberg syndrome characterised by dysplastic elbow joints and the fusion of wrist bones and the consequent radial deviation. With upper limb features resembling some of those seen in the lower limb.

The deletions seen in affected individuals range from 8kb to 134kb in size and are thought to result in overexpression of PITX1 by affecting the proximity between the coding sequence and an upstream enhancer (referred to variably as 'Pen' or 'hs1473').
The deletion removes part of a different protein coding gene - MACROH2A1 which is not thought to contribute to the pathogenesis (knockout mice do not present with a similar phenotype to Liebenberg).
Authors of PMID: 30711920 suggest the promoter of MACROH2A1 acts as an insulator between the upstream enhancer and PITX1 however further functional studies are required to establish this.

Functional studies involving transgenic mice with the enhancer element just upstream of PITX1 resulting in a similar phenotype to affected individuals.

Note: Maximal reported deletion coordinates at time of writing: chr5:135288912-135423802
Minimum: chr5:135393716-135402219:
Sources: Literature
Monogenic Diabetes v0.213 POC1A Chirag Patel Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357
Monogenic Diabetes v0.212 POC1A Chirag Patel Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813 to Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894
Monogenic Diabetes v0.211 POC1A Chirag Patel reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39662966; Phenotypes: Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, MONDO:0013894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.211 Chirag Patel Copied gene POC1A from panel Mendeliome
Monogenic Diabetes v0.211 POC1A Chirag Patel gene: POC1A was added
gene: POC1A was added to Monogenic Diabetes. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POC1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357
Phenotypes for gene: POC1A were set to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813
Intellectual disability syndromic and non-syndromic v1.713 Chirag Patel Added reviews for gene POC1A from panel Mendeliome
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel Marked gene: PCSK1 as ready
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel Gene: pcsk1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel Marked gene: PCSK1 as ready
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel Gene: pcsk1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.196 Chirag Patel Copied gene PCSK1 from panel Adrenal insufficiency
Pituitary hormone deficiency v0.196 PCSK1 Chirag Patel gene: PCSK1 was added
gene: PCSK1 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCSK1 were set to 30383237
Phenotypes for gene: PCSK1 were set to Obesity with impaired prohormone processing MIM#600955
Hypogonadotropic hypogonadism v0.99 Chirag Patel Copied gene PCSK1 from panel Adrenal insufficiency
Hypogonadotropic hypogonadism v0.99 PCSK1 Chirag Patel gene: PCSK1 was added
gene: PCSK1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCSK1 were set to 30383237
Phenotypes for gene: PCSK1 were set to Obesity with impaired prohormone processing MIM#600955
Adrenal insufficiency v0.76 PCSK1 Chirag Patel changed review comment from: adrenal insufficiency seen in condition; to: Various endocrine disorders present as disease progresses, including GH deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%).
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Cholestasis v1.9 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Cholestasis v1.9 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel Marked gene: NUDCD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.546 Chirag Patel Added reviews for gene NUDCD2 from panel Mendeliome
Congenital hypothyroidism v0.105 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Congenital hypothyroidism v0.105 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Congenital hypothyroidism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Cholestasis v1.9 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Cholestasis v1.9 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Cholestasis. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Cerebellar and Pontocerebellar Hypoplasia v1.99 Chirag Patel Copied gene NUDCD2 from panel Mendeliome
Cerebellar and Pontocerebellar Hypoplasia v1.99 NUDCD2 Chirag Patel gene: NUDCD2 was added
gene: NUDCD2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Mendeliome v1.4624 NUDCD2 Chirag Patel reviewed gene: NUDCD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37272762; Phenotypes: Multiple congenital anomalies (MONDO:0019042), NUDCD2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.98 POLR3A Chirag Patel Marked gene: POLR3A as ready
Hypogonadotropic hypogonadism v0.98 POLR3A Chirag Patel Gene: polr3a has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 PNPLA6 Chirag Patel Marked gene: PNPLA6 as ready
Hypogonadotropic hypogonadism v0.98 PNPLA6 Chirag Patel Gene: pnpla6 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 PLXNA3 Chirag Patel Marked gene: PLXNA3 as ready
Hypogonadotropic hypogonadism v0.98 PLXNA3 Chirag Patel Gene: plxna3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 OTX2 Chirag Patel Marked gene: OTX2 as ready
Hypogonadotropic hypogonadism v0.98 OTX2 Chirag Patel Gene: otx2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 NR0B1 Chirag Patel Marked gene: NR0B1 as ready
Hypogonadotropic hypogonadism v0.98 NR0B1 Chirag Patel Gene: nr0b1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 NOS1 Chirag Patel Marked gene: NOS1 as ready
Hypogonadotropic hypogonadism v0.98 NOS1 Chirag Patel Gene: nos1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHX4 Chirag Patel Marked gene: LHX4 as ready
Hypogonadotropic hypogonadism v0.98 LHX4 Chirag Patel Gene: lhx4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHX3 Chirag Patel Marked gene: LHX3 as ready
Hypogonadotropic hypogonadism v0.98 LHX3 Chirag Patel Gene: lhx3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 LHB Chirag Patel Marked gene: LHB as ready
Hypogonadotropic hypogonadism v0.98 LHB Chirag Patel Gene: lhb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 KLB Chirag Patel Marked gene: KLB as ready
Hypogonadotropic hypogonadism v0.98 KLB Chirag Patel Gene: klb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 KISS1R Chirag Patel Marked gene: KISS1R as ready
Hypogonadotropic hypogonadism v0.98 KISS1R Chirag Patel Gene: kiss1r has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 HID1 Chirag Patel Marked gene: HID1 as ready
Hypogonadotropic hypogonadism v0.98 HID1 Chirag Patel Gene: hid1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 HESX1 Chirag Patel Marked gene: HESX1 as ready
Hypogonadotropic hypogonadism v0.98 HESX1 Chirag Patel Gene: hesx1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNRHR Chirag Patel Marked gene: GNRHR as ready
Hypogonadotropic hypogonadism v0.98 GNRHR Chirag Patel Gene: gnrhr has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNRH1 Chirag Patel Marked gene: GNRH1 as ready
Hypogonadotropic hypogonadism v0.98 GNRH1 Chirag Patel Gene: gnrh1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GNAI2 Chirag Patel Marked gene: GNAI2 as ready
Hypogonadotropic hypogonadism v0.98 GNAI2 Chirag Patel Gene: gnai2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GLI3 Chirag Patel Marked gene: GLI3 as ready
Hypogonadotropic hypogonadism v0.98 GLI3 Chirag Patel Gene: gli3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 GLI2 Chirag Patel Marked gene: GLI2 as ready
Hypogonadotropic hypogonadism v0.98 GLI2 Chirag Patel Gene: gli2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FSHB Chirag Patel Marked gene: FSHB as ready
Hypogonadotropic hypogonadism v0.98 FSHB Chirag Patel Gene: fshb has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Hypogonadotropic hypogonadism v0.98 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGFR1 Chirag Patel Marked gene: FGFR1 as ready
Hypogonadotropic hypogonadism v0.98 FGFR1 Chirag Patel Gene: fgfr1 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGF8 Chirag Patel Marked gene: FGF8 as ready
Hypogonadotropic hypogonadism v0.98 FGF8 Chirag Patel Gene: fgf8 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 FGF17 Chirag Patel Marked gene: FGF17 as ready
Hypogonadotropic hypogonadism v0.98 FGF17 Chirag Patel Gene: fgf17 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 EIF2S3 Chirag Patel Marked gene: EIF2S3 as ready
Hypogonadotropic hypogonadism v0.98 EIF2S3 Chirag Patel Gene: eif2s3 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 DCAF17 Chirag Patel Marked gene: DCAF17 as ready
Hypogonadotropic hypogonadism v0.98 DCAF17 Chirag Patel Gene: dcaf17 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 CUL4B Chirag Patel Marked gene: CUL4B as ready
Hypogonadotropic hypogonadism v0.98 CUL4B Chirag Patel Gene: cul4b has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 CHD7 Chirag Patel Marked gene: CHD7 as ready
Hypogonadotropic hypogonadism v0.98 CHD7 Chirag Patel Gene: chd7 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 BMP4 Chirag Patel Marked gene: BMP4 as ready
Hypogonadotropic hypogonadism v0.98 BMP4 Chirag Patel Gene: bmp4 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 ARHGAP35 Chirag Patel Marked gene: ARHGAP35 as ready
Hypogonadotropic hypogonadism v0.98 ARHGAP35 Chirag Patel Gene: arhgap35 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.98 ANOS1 Chirag Patel Marked gene: ANOS1 as ready
Hypogonadotropic hypogonadism v0.98 ANOS1 Chirag Patel Gene: anos1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.210 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Monogenic Diabetes v0.210 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.209 SLC40A1 Chirag Patel reviewed gene: SLC40A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.195 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Pituitary hormone deficiency v0.195 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.194 SLC40A1 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Marked gene: SLC40A1 as ready
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.98 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.97 SLC40A1 Chirag Patel Classified gene: SLC40A1 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.97 SLC40A1 Chirag Patel Gene: slc40a1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.96 SLC40A1 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Monogenic Diabetes v0.209 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Monogenic Diabetes v0.209 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.208 HAMP Chirag Patel reviewed gene: HAMP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Marked gene: HAMP as ready
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Hypogonadotropic hypogonadism v0.96 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.95 HAMP Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.194 HAMP Chirag Patel Classified gene: HAMP as Red List (low evidence)
Pituitary hormone deficiency v0.194 HAMP Chirag Patel Gene: hamp has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.193 HAMP Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Marked gene: TFR2 as ready
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.95 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.94 TFR2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.193 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Pituitary hormone deficiency v0.193 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.192 TFR2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Monogenic Diabetes v0.208 TFR2 Chirag Patel Classified gene: TFR2 as Red List (low evidence)
Monogenic Diabetes v0.208 TFR2 Chirag Patel Gene: tfr2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.207 TFR2 Chirag Patel reviewed gene: TFR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.192 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Marked gene: HFE2 as ready
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Hypogonadotropic hypogonadism v0.94 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.93 HFE2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.192 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Pituitary hormone deficiency v0.192 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel Deleted their comment
Pituitary hormone deficiency v0.191 HFE2 Chirag Patel edited their review of gene: HFE2: Added comment: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.; Changed rating: RED
Pituitary hormone deficiency v0.191 HFE Chirag Patel changed review comment from: Late complication of disease with low lifetime penetrance - not suitable for this panel.; to: Hypogonadotropic hypogonadism is late complication of disease with low lifetime penetrance - not suitable for this panel.
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Marked gene: HFE as ready
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Hypogonadotropic hypogonadism v0.93 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.92 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE Chirag Patel changed review comment from: Hypogonadotropic hypogonadism is a feature; to: Late complication of disease with low lifetime penetrance - not suitable for this panel.
Pituitary hormone deficiency v0.191 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Pituitary hormone deficiency v0.191 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.190 Chirag Patel Added reviews for gene HFE2 from panel Monogenic Diabetes
Hypogonadotropic hypogonadism v0.92 Chirag Patel Added reviews for gene HFE2 from panel Monogenic Diabetes
Monogenic Diabetes v0.207 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Monogenic Diabetes v0.207 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.206 HFE2 Chirag Patel Classified gene: HFE2 as Red List (low evidence)
Monogenic Diabetes v0.206 HFE2 Chirag Patel Gene: hfe2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.205 HFE2 Chirag Patel reviewed gene: HFE2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pituitary hormone deficiency v0.189 Chirag Patel Added reviews for gene HFE from panel Monogenic Diabetes
Hypogonadotropic hypogonadism v0.91 Chirag Patel Added reviews for gene HFE from panel Monogenic Diabetes
Monogenic Diabetes v0.205 HFE Chirag Patel Classified gene: HFE as Red List (low evidence)
Monogenic Diabetes v0.205 HFE Chirag Patel Gene: hfe has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.204 HFE Chirag Patel reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Marked gene: NSD1 as ready
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Classified gene: NSD1 as Amber List (moderate evidence)
Congenital hypothyroidism v0.104 NSD1 Chirag Patel Gene: nsd1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.103 NSD1 Chirag Patel gene: NSD1 was added
gene: NSD1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NSD1 were set to 41024235; 34350334; 15942875
Phenotypes for gene: NSD1 were set to Sotos syndrome, MONDO:0019349
Review for gene: NSD1 was set to AMBER
Added comment: 3 individuals with Sotos syndrome and heterozygous loss‑of‑function NSD1 variants, with permanent congenital hypothyroidism. Congenital hypothyroidism in Sotos syndrome may be an underreported feature.
Sources: Literature
Mendeliome v1.4624 Chirag Patel Added reviews for gene NNT from panel Congenital hypothyroidism
Congenital hypothyroidism v0.102 NNT Chirag Patel changed review comment from: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid dysgenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature; to: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid agenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature
Congenital hypothyroidism v0.102 NNT Chirag Patel Marked gene: NNT as ready
Congenital hypothyroidism v0.102 NNT Chirag Patel Gene: nnt has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.102 NNT Chirag Patel gene: NNT was added
gene: NNT was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: NNT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NNT were set to 34545694
Phenotypes for gene: NNT were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: NNT was set to RED
Added comment: PMID 34545694 describes 3 unrelated families with 3 heterozygous missense NNT variants that produce permanent congenital hypothyroidism due to thyroid dysgenesis. (p.Ala271Ser, p.Arg693His, p.Val861Met). There is no segregation information and the p.Arg693His variant is common in gnomAD. Functional assays (western blot, measurement of NADPH/NADPtotal and H2O2 generation, cell proliferation, and wounding healing assay) showed damaging effect of the NNT variants on stability and catalytic activity of proteins and redox balance of cells, which might lead to the abnormal development of thyroid gland.
Sources: Literature
Hand and foot malformations v0.83 Sarah Milton Copied Region IHH upstream regulatory region from panel Mendeliome
Hand and foot malformations v0.83 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Hand and foot malformations. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Craniosynostosis v1.76 Sarah Milton Copied Region IHH upstream regulatory region from panel Mendeliome
Craniosynostosis v1.76 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Craniosynostosis. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Mendeliome v1.4623 IHH upstream regulatory region Sarah Milton Region: IHH upstream regulatory region was added
Region: IHH upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: IHH upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: IHH upstream regulatory region were set to PMID: 21167467
Phenotypes for Region: IHH upstream regulatory region were set to Craniosynostosis, Philadelphia type, with syndactyly, MIM#185900; Syndactyly, type 1, MIM#185900
Review for Region: IHH upstream regulatory region was set to GREEN
Added comment: IHH belongs to the hedgehog family, and is required for endochondral bone formation by regulating the proliferation and differentiation of chondrocytes. During development IHH is predominantly expressed in prehypertrophic chondrocytes.

PMID: 21167467 describes 3 families with over 80 affected individuals with duplications either including IHH or entirely upstream (in an intron of NHEJ1). These individuals were affected with variable degrees of cutaneous and distal osseus syndactyly and craniosynostosis.

Authors identified duplications in affected families involving conserved non coding elements (either 1 or up to 3 in those with the largest duplications) and cloned an orthologous region into mouse with a fluorescent reporter vector and found staining of chondrocytes indicating this region was a possible enhancer.

Note: OMIM uses coordinates chr2:208,200,001-230,100,000 for this duplication (maximal breakpoints). Minimal region overlap from literature used for Panelapp entry. Further functional studies required to define exact breakpoints.
Sources: Literature
Mendeliome v1.4622 TUBA4A Zornitza Stark Deleted their review
Mendeliome v1.4622 TUBA4A Zornitza Stark Publications for gene: TUBA4A were set to PMID: 38413182
Mendeliome v1.4621 TUBA4A Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4620 Zornitza Stark Added reviews for gene TUBA4A from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4619 GBP1 Chirag Patel Marked gene: GBP1 as ready
Mendeliome v1.4619 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4619 GBP1 Chirag Patel Marked gene: GBP1 as ready
Mendeliome v1.4619 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.418 KYNU Chirag Patel Marked gene: KYNU as ready
Skeletal dysplasia v0.418 KYNU Chirag Patel Gene: kynu has been classified as Green List (High Evidence).
Skeletal dysplasia v0.418 KYNU Chirag Patel commented on gene: KYNU
Skeletal dysplasia v0.418 Chirag Patel Copied gene KYNU from panel Mendeliome
Skeletal dysplasia v0.418 KYNU Chirag Patel gene: KYNU was added
gene: KYNU was added to Skeletal dysplasia. Sources: Expert Review Green,NHS GMS,Victorian Clinical Genetics Services
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 17334708; 28792876; 31923704
Phenotypes for gene: KYNU were set to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v1.4619 Chirag Patel Copied gene GBP1 from panel Congenital hypothyroidism
Mendeliome v1.4619 GBP1 Chirag Patel gene: GBP1 was added
gene: GBP1 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GBP1 was set to Unknown
Publications for gene: GBP1 were set to 34194003
Phenotypes for gene: GBP1 were set to Congenital hypothyroidism, MONDO:0018612
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Marked gene: GBP1 as ready
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.101 GBP1 Chirag Patel reviewed gene: GBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34194003; Phenotypes: Congenital hypothyroidism, MONDO:0018612; Mode of inheritance: Unknown
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Deleted their review
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Deleted their comment
Congenital hypothyroidism v0.101 GBP1 Chirag Patel Mode of inheritance for gene: GBP1 was changed from BIALLELIC, autosomal or pseudoautosomal to Unknown
Congenital hypothyroidism v0.100 GBP1 Chirag Patel Classified gene: GBP1 as Amber List (moderate evidence)
Congenital hypothyroidism v0.100 GBP1 Chirag Patel Gene: gbp1 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.99 GBP1 Chirag Patel gene: GBP1 was added
gene: GBP1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: GBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBP1 were set to 34194003
Phenotypes for gene: GBP1 were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: GBP1 was set to AMBER
Added comment: PMID 34194003 reports 3 individuals from 3 unrelated families presenting with congenital hypothyroidism (neonatal onset, elevated TSH, low thyroid hormone, thyroid dysgenesis or diffuse hypoechoic thyroid). 1 individual had biallelic variants (p.E336fs and p.H150Y1) with parents as heterozygous unaffected carriers. The other 2 individuals had a heterozygous variant (p.R20X or p.L187P) inherited from an unaffected parent. Methylation-specific PCR and pyrosequencing found the CpG site of GBP1 was hypermethylated in the genomic DNA isolated from the 2 probands compared with their euthyroid parents.

Zebrafish morpholino knockdown of gbp1 causes thyroid primordium malformation and hypothyroidism. The phenotype was rescued by wild‑type human GBP1 mRNA but not by mutant p.H150Y or p.L187P. Human TPC1 thyroid cells expressing mutant GBP1 show mislocalisation, loss of β‑catenin interaction and disrupted adhesion complex formation.
Sources: Literature
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Marked gene: FOXP3 as ready
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Gene: foxp3 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Classified gene: FOXP3 as Amber List (moderate evidence)
Congenital hypothyroidism v0.98 FOXP3 Chirag Patel Gene: foxp3 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.97 FOXP3 Chirag Patel reviewed gene: FOXP3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital hypothyroidism v0.97 Chirag Patel Copied gene FOXP3 from panel Mendeliome
Congenital hypothyroidism v0.97 FOXP3 Chirag Patel gene: FOXP3 was added
gene: FOXP3 was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
treatable tags were added to gene: FOXP3.
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 11295725; 11137993; 33668198; 33614561; 33330291; 32234571
Phenotypes for gene: FOXP3 were set to Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790
Ataxia v1.197 DNAJC3 Chirag Patel Marked gene: DNAJC3 as ready
Ataxia v1.197 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Ataxia v1.197 Chirag Patel Copied gene DNAJC3 from panel Congenital hypothyroidism
Ataxia v1.197 DNAJC3 Chirag Patel gene: DNAJC3 was added
gene: DNAJC3 was added to Ataxia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 34654017; 34630333; 33486469; 32738013; 28940199
Phenotypes for gene: DNAJC3 were set to juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome, MONDO:0014523
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Marked gene: DNAJC3 as ready
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Classified gene: DNAJC3 as Green List (high evidence)
Congenital hypothyroidism v0.96 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.95 DNAJC3 Chirag Patel gene: DNAJC3 was added
gene: DNAJC3 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 34654017; 34630333; 33486469; 32738013; 28940199
Phenotypes for gene: DNAJC3 were set to juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome, MONDO:0014523
Review for gene: DNAJC3 was set to GREEN
Added comment: 14 individuals from 8 unrelated families with biallelic variants in DNAJC3, presenting with congenital/early‑onset hypothyroidism, early‑onset diabetes mellitus, neuropathy, cerebellar ataxia, progressive neurodegeneration, short stature, and sensorineural hearing loss.
Sources: Literature
Mendeliome v1.4618 LSM7 Sangavi Sivagnanasundram edited their review of gene: LSM7: Added comment: Addition of publication - GDA remain as AMBER as no new evidence as been reported; Changed publications: 39420558, 35047835; Changed phenotypes: Neurodevelopmental disorder with leukodystrophy and cerebellar atrophy MONDO:0700092
Hypogonadotropic hypogonadism v0.90 CPE Chirag Patel Phenotypes for gene: CPE were changed from Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 to BDV syndrome MONDO:0859150
Hypogonadotropic hypogonadism v0.89 CPE Chirag Patel Marked gene: CPE as ready
Hypogonadotropic hypogonadism v0.89 CPE Chirag Patel Gene: cpe has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.89 Chirag Patel Added reviews for gene CPE from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.188 CPE Chirag Patel Publications for gene: CPE were set to 26120850; 32936766; 34383079
Pituitary hormone deficiency v0.187 CPE Chirag Patel Phenotypes for gene: CPE were changed from Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326 to BDV syndrome MONDO:0859150
Pituitary hormone deficiency v0.186 CPE Chirag Patel Marked gene: CPE as ready
Pituitary hormone deficiency v0.186 CPE Chirag Patel Gene: cpe has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.186 CPE Chirag Patel reviewed gene: CPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 34383079, 26120850,32936766; Phenotypes: BDV syndrome MONDO:0859150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.196 RAB3A Zornitza Stark Phenotypes for gene: RAB3A were changed from autosomal dominant cerebellar ataxia MONDO:0020380 to Spinocerebellar ataxia 52, MIM# 621535
Ataxia v1.195 RAB3A Zornitza Stark reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 52, MIM# 621535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4618 RAB3A Zornitza Stark Phenotypes for gene: RAB3A were changed from autosomal dominant cerebellar ataxia MONDO:0020380; neurodevelopmental disorder MONDO:0700092 to Spinocerebellar ataxia 52, MIM# 621535; neurodevelopmental disorder MONDO:0700092
Pituitary hormone deficiency v0.186 Chirag Patel Copied gene CPE from panel Mendeliome
Pituitary hormone deficiency v0.186 CPE Chirag Patel gene: CPE was added
gene: CPE was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Hypogonadotropic hypogonadism v0.88 Chirag Patel Copied gene CPE from panel Mendeliome
Hypogonadotropic hypogonadism v0.88 CPE Chirag Patel gene: CPE was added
gene: CPE was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Mendeliome v1.4617 RAB3A Zornitza Stark reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 52, MIM# 621535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital hypothyroidism v0.94 CDC42 Chirag Patel Publications for gene: CDC42 were set to 30872706; 29335451
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Marked gene: CDC42 as ready
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Gene: cdc42 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Classified gene: CDC42 as Amber List (moderate evidence)
Congenital hypothyroidism v0.93 CDC42 Chirag Patel Gene: cdc42 has been classified as Amber List (Moderate Evidence).
Congenital hypothyroidism v0.92 CDC42 Chirag Patel gene: CDC42 was added
gene: CDC42 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to 30872706; 29335451
Phenotypes for gene: CDC42 were set to Congenital hypothyroidism, MONDO:0018612
Review for gene: CDC42 was set to AMBER
Added comment: ClinGen DEFINITIVE for Takenouchi-Kosaki syndrome (Oct 2021).

3 individuals with Takenouchi-Kosaki syndrome and congenital hypothyroidism. They all had the same rare de novo missense variant in CDC42 (p.Tyr64Cys). C. elegans knock‑in model demonstrated a hypomorphic loss‑of‑function effect. (NB 1 overlapping family between PMID 29335451 and PMID 30872706)
Sources: Literature
Congenital hypothyroidism v0.91 DUOX1 Chirag Patel edited their review of gene: DUOX1: Added comment: PMID 31428054:
1 individual with congenital hypothyroidism with heterozygous missense variant in DUOX1 (p.R1307Q). No segregation testing and variant is too common in gnomAD. HeLa cell overexpression of the p.R1307Q mutant showed reduced DUOX1 mRNA, protein and H₂O₂ production.

PMID 27373559:
1 individual with congenital hypothyroidism with heterozygous missense variant in DUOX1 (p.P219L). No segregation testing and no functional testing, and variant is too common in gnomAD.

PMID 33631011:
14 individuals with congenital hypothyroidism with DUOX1 variants (13 missense, 1 nonsense), BUT no information on individual phenotypes, segregation data, or functional validation.; Changed rating: RED; Changed publications: 31428054, 27373559, 33631011:; Changed phenotypes: Congenital hypothyroidism, MONDO:0018612; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.712 TRIM71 Zornitza Stark Publications for gene: TRIM71 were set to 29983323; 32168371; 30975633; 40892928
Intellectual disability syndromic and non-syndromic v1.711 TRIM71 Zornitza Stark edited their review of gene: TRIM71: Added comment: PMID 38833623 reports 20 individuals from 13 unrelated families with heterozygous de novo or rare inherited TRIM71 variants (missense, nonsense, splice‑site, frameshift) presenting with congenital hydrocephalus/ventriculomegaly, developmental delay, dysmorphic features, corpus callosum dysgenesis, white‑matter hypoplasia, limb and craniofacial anomalies, hearing and cardiac defects. Functional studies in HEK293T cells show NHL‑domain missense variants impair binding to CDKN1A/EGR1 and disrupt P‑body localization, supporting loss‑of‑function/altered‑function mechanisms.; Changed publications: 40892928, 38833623
Intellectual disability syndromic and non-syndromic v1.711 Zornitza Stark Copied gene TRIM71 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.711 TRIM71 Zornitza Stark gene: TRIM71 was added
gene: TRIM71 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to 29983323; 32168371; 30975633; 40892928
Phenotypes for gene: TRIM71 were set to Congenital hydrocephalus 4 (MIM#618667)
Mendeliome v1.4617 TRIM71 Zornitza Stark Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Mendeliome v1.4616 TRIM71 Zornitza Stark changed review comment from: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.; to: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.

Likely phenotype expansion.
Mendeliome v1.4616 TRIM71 Zornitza Stark reviewed gene: TRIM71: Rating: GREEN; Mode of pathogenicity: None; Publications: 40892928; Phenotypes: Congenital hydrocephalus 4 (MIM#618667); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Classified gene: TRIM71 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.340 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.339 TRIM71 Zornitza Stark gene: TRIM71 was added
gene: TRIM71 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM71 were set to 40892928
Phenotypes for gene: TRIM71 were set to Congenital hydrocephalus 4 (MIM#618667)
Review for gene: TRIM71 was set to GREEN
Added comment: Reports 3 individuals from 3 unrelated families with heterozygous missense TRIM71 variants (p.Q334R, p.R608H, p.R796H) presenting with childhood‑onset syndromic hearing loss, often accompanied by congenital hydrocephalus, renal cysts, facial dysmorphism and other developmental anomalies. Two individuals (p.Q334R and p.R608H) have detailed clinical work‑up (sensorineural or mixed severe loss, inner ear malformations) and functional assays demonstrate that p.Q334R mis‑localises TRIM71 to P‑bodies and p.R608H disrupts RNA binding. Mouse models with loss‑of‑function or the human HL‑associated missense allele recapitulate severe hearing loss, confirming the pathogenic mechanism as loss‑of‑function of TRIM71.
Sources: Literature
Mendeliome v1.4616 TNFRSF11A Zornitza Stark Phenotypes for gene: TNFRSF11A were changed from Osteopetrosis, autosomal recessive 7 - MIM# 612301 to Osteopetrosis, autosomal recessive 7 - MIM# 612301; familial expansile osteolysis, MONDO:0008275
Mendeliome v1.4615 TNFRSF11A Zornitza Stark Publications for gene: TNFRSF11A were set to 18606301; 32048120
Mendeliome v1.4614 TNFRSF11A Zornitza Stark Mode of inheritance for gene: TNFRSF11A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4613 TNFRSF11A Zornitza Stark edited their review of gene: TNFRSF11A: Added comment: Two independent studies (PMID 36740137, PMID 40222603) document three unrelated families with heterozygous exon‑1 in‑frame duplications (c.52_63dup, c.39_65dup) that act as gain‑of‑function alleles, producing a dominant dento‑osseous / familial expansile osteolysis phenotype with hearing loss, tooth root resorption and tendon avulsion.; Changed publications: 10.64898/2026.02.18.706528, 40222603, 36740137, 35812760, 33037392, 31163101; Changed phenotypes: familial expansile osteolysis, MONDO:0008275; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.35 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Hereditary predisposition to infections, MONDO:0015979, TBK1-related
Defects of intrinsic and innate immunity v1.34 TBK1 Zornitza Stark Publications for gene: TBK1 were set to
Defects of intrinsic and innate immunity v1.33 TBK1 Zornitza Stark Mode of inheritance for gene: TBK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v1.22 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381
Mandibulofacial Acrofacial dysostosis v1.21 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark Deleted their comment
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.20 Zornitza Stark Copied gene POLD1 from panel Mendeliome
Mandibulofacial Acrofacial dysostosis v1.20 POLD1 Zornitza Stark gene: POLD1 was added
gene: POLD1 was added to Mandibulofacial Acrofacial dysostosis. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POLD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLD1 were set to 31629014; 31449058; 23770608; 33618333; 33369179; 32826474; 30023403; 29199204; 28791128
Phenotypes for gene: POLD1 were set to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836
Incidentalome v0.433 OPTN Zornitza Stark Marked gene: OPTN as ready
Incidentalome v0.433 OPTN Zornitza Stark Gene: optn has been classified as Green List (High Evidence).
Incidentalome v0.433 OPTN Zornitza Stark Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MONDO: 0013264, MIM#613435)
Incidentalome v0.432 OPTN Zornitza Stark Publications for gene: OPTN were set to
Incidentalome v0.431 OPTN Zornitza Stark Mode of inheritance for gene: OPTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.545 NUS1 Zornitza Stark Classified gene: NUS1 as Red List (low evidence)
Fetal anomalies v1.545 NUS1 Zornitza Stark Gene: nus1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.544 NUS1 Zornitza Stark edited their review of gene: NUS1: Added comment: Limited evidence for the AR disorder, little if any replication over time which is concerning. Monoallelic disorder lacks prenatal findings.; Changed rating: RED
Mendeliome v1.4613 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Congenital disorder of glycosylation, type 1aa 617082; Mental retardation, autosomal dominant 55, with seizures 617831 to Intellectual developmental disorder, autosomal dominant 55, with seizures, MIM# 617831
Mendeliome v1.4612 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 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
Mendeliome v1.4611 NUS1 Zornitza Stark reviewed gene: NUS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1aa, MIM# 617082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.84 NUS1 Zornitza Stark Classified gene: NUS1 as Red List (low evidence)
Congenital Disorders of Glycosylation v1.84 NUS1 Zornitza Stark Gene: nus1 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v1.83 NUS1 Zornitza Stark reviewed gene: NUS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type 1aa, MIM# 617082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Marked gene: KNG1 as ready
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Gene: kng1 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.76 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234 to congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Bleeding and Platelet Disorders v1.75 KNG1 Zornitza Stark Publications for gene: KNG1 were set to 41634406; 40848077; 36700498; 33114181; 32185598; 31858768; 31087670
Bleeding and Platelet Disorders v1.74 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark Deleted their comment
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark Deleted their comment
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark edited their review of gene: KNG1: Changed publications: 36700498; Changed phenotypes: congenital high-molecular-weight kininogen deficiency, MONDO:0009234; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.73 Zornitza Stark Copied gene KNG1 from panel Mendeliome
Bleeding and Platelet Disorders v1.73 KNG1 Zornitza Stark gene: KNG1 was added
gene: KNG1 was added to Bleeding and Platelet Disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KNG1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KNG1 were set to 41634406; 40848077; 36700498; 33114181; 32185598; 31858768; 31087670
Phenotypes for gene: KNG1 were set to angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Mendeliome v1.4611 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from Hereditary angioedema-6 (HAE6), MIM#619363 to angioedema, hereditary, 6, MONDO:0023660; congenital high-molecular-weight kininogen deficiency, MONDO:0009234
Mendeliome v1.4610 KNG1 Zornitza Stark Publications for gene: KNG1 were set to 31087670; 33114181
Mendeliome v1.4609 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4608 KNG1 Zornitza Stark edited their review of gene: KNG1: Added comment: PMID 36700498 aggregates 48 patients from 41 unrelated families with biallelic truncating or splice‑site KNG1 variants. Prolonged aPTT and but lack of evidence for increased incidence of major bleeding episodes.; Changed publications: 41634406, 40848077, 36700498, 33114181, 32185598, 31858768, 31087670; Changed phenotypes: angioedema, hereditary, 6, MONDO:0023660, congenital high-molecular-weight kininogen deficiency, MONDO:0009234; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Desmosomal disorders v1.4 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Desmosomal disorders v1.4 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Desmosomal disorders v1.4 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia 257980 AR Schopf-Schulz-Passarge syndrome 224750 AR Tooth agenesis, selective, 4 150400 AR, AD
Desmosomal disorders v1.3 WNT10A Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Desmosomal disorders v1.2 WNT10A Zornitza Stark Publications for gene: WNT10A were set to
Desmosomal disorders v1.1 WNT10A Zornitza Stark Classified gene: WNT10A as Red List (low evidence)
Desmosomal disorders v1.1 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Desmosomal disorders v1.0 WNT10A Zornitza Stark reviewed gene: WNT10A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Desmosomal disorders v1.0 Zornitza Stark promoted panel to version 1.0
Desmosomal disorders v0.40 DSG3 Zornitza Stark Marked gene: DSG3 as ready
Desmosomal disorders v0.40 DSG3 Zornitza Stark Gene: dsg3 has been classified as Amber List (Moderate Evidence).
Desmosomal disorders v0.40 Zornitza Stark Copied gene DSG3 from panel Epidermolysis bullosa
Desmosomal disorders v0.40 DSG3 Zornitza Stark gene: DSG3 was added
gene: DSG3 was added to Desmosomal disorders. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: DSG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSG3 were set to 26763450; 37850634; 30528827
Phenotypes for gene: DSG3 were set to Blistering, acantholytic, of oral and laryngeal mucosa, MIM# 619226
Desmosomal disorders v0.39 TP63 Zornitza Stark Marked gene: TP63 as ready
Desmosomal disorders v0.39 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Desmosomal disorders v0.39 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to Rapp-Hodgkin syndrome, MIM# 129400
Desmosomal disorders v0.38 TP63 Zornitza Stark Mode of inheritance for gene: TP63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.37 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rapp-Hodgkin syndrome, MIM# 129400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.37 EDARADD Zornitza Stark Marked gene: EDARADD as ready
Desmosomal disorders v0.37 EDARADD Zornitza Stark Gene: edaradd has been classified as Green List (High Evidence).
Desmosomal disorders v0.37 DSP Zornitza Stark Marked gene: DSP as ready
Desmosomal disorders v0.37 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Desmosomal disorders v0.37 DSP Zornitza Stark Phenotypes for gene: DSP were changed from to Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821
Desmosomal disorders v0.36 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.35 DSP Zornitza Stark reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Corneal Dystrophy v1.21 TUBA3D Zornitza Stark Marked gene: TUBA3D as ready
Corneal Dystrophy v1.21 TUBA3D Zornitza Stark Gene: tuba3d has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v1.7 PHOX2B_CCHS_GCN Zornitza Stark Marked STR: PHOX2B_CCHS_GCN as ready
Central Hypoventilation v1.7 PHOX2B_CCHS_GCN Zornitza Stark Str: phox2b_cchs_gcn has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v1.0 Zornitza Stark promoted panel to version 1.0
Cataract v1.0 Zornitza Stark promoted panel to version 1.0
Cataract v0.631 ELP4 Zornitza Stark Marked gene: ELP4 as ready
Cataract v0.631 ELP4 Zornitza Stark Gene: elp4 has been classified as Green List (High Evidence).
Cataract v0.631 CRYBA2 Zornitza Stark Marked gene: CRYBA2 as ready
Cataract v0.631 CRYBA2 Zornitza Stark Gene: cryba2 has been classified as Green List (High Evidence).
Autonomic neuropathy v1.2 Zornitza Stark HPO terms changed from Abnormality of the autonomic nervous system HP:0002270 to
List of related panels changed from to Abnormality of the autonomic nervous system HP:0002270
Autonomic neuropathy v1.1 Zornitza Stark HPO terms changed from to Abnormality of the autonomic nervous system HP:0002270
Autonomic neuropathy v1.0 Zornitza Stark promoted panel to version 1.0
Autonomic neuropathy v0.51 NGF Zornitza Stark Marked gene: NGF as ready
Autonomic neuropathy v0.51 NGF Zornitza Stark Gene: ngf has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v1.0 Zornitza Stark promoted panel to version 1.0
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Marked gene: DGKE as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Gene: dgke has been classified as Red List (Low Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.68 DGKE Zornitza Stark Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7, MIM# 615008
Atypical Haemolytic Uraemic Syndrome_MPGN v0.67 DGKE Zornitza Stark Publications for gene: DGKE were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.66 DGKE Zornitza Stark Mode of inheritance for gene: DGKE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Atypical Haemolytic Uraemic Syndrome_MPGN v0.65 DGKE Zornitza Stark Classified gene: DGKE as Red List (low evidence)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.65 DGKE Zornitza Stark Gene: dgke has been classified as Red List (Low Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 DGKE Zornitza Stark edited their review of gene: DGKE: Added comment: Not appropriate for this panel, causes nephrotic syndrome.; Changed rating: RED
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Marked gene: CFI as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.64 CFI Zornitza Stark Phenotypes for gene: CFI were changed from to {Haemolytic uremic syndrome, atypical, susceptibility to, 3} MIM#612923
Atypical Haemolytic Uraemic Syndrome_MPGN v0.63 CFI Zornitza Stark Publications for gene: CFI were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.62 CFI Zornitza Stark Mode of inheritance for gene: CFI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Marked gene: CFHR5 as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Gene: cfhr5 has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.61 CFHR5 Zornitza Stark Phenotypes for gene: CFHR5 were changed from to Nephropathy due to CFHR5 deficiency, MIM#614809
Atypical Haemolytic Uraemic Syndrome_MPGN v0.60 CFHR5 Zornitza Stark Publications for gene: CFHR5 were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.59 CFHR5 Zornitza Stark Mode of inheritance for gene: CFHR5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Marked gene: CFH as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.58 CFH Zornitza Stark Phenotypes for gene: CFH were changed from to {Haemolytic uremic syndrome, atypical, susceptibility to, 1} MIMI#235400
Atypical Haemolytic Uraemic Syndrome_MPGN v0.57 CFH Zornitza Stark Publications for gene: CFH were set to
Atypical Haemolytic Uraemic Syndrome_MPGN v0.56 CFH Zornitza Stark Mode of inheritance for gene: CFH was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v1.0 Zornitza Stark promoted panel to version 1.0
Arrhythmogenic Cardiomyopathy v0.78 CTNNA3 Zornitza Stark Marked gene: CTNNA3 as ready
Arrhythmogenic Cardiomyopathy v0.78 CTNNA3 Zornitza Stark Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v1.0 Zornitza Stark promoted panel to version 1.0
Renal Macrocystic Disease v1.0 Chirag Patel promoted panel to version 1.0
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Marked gene: CFAP47 as ready
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Classified gene: CFAP47 as Red List (low evidence)
Renal Macrocystic Disease v0.112 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.111 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis-2, MIM# 613254
Renal Macrocystic Disease v0.110 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.109 ISCA-37432-Loss Zornitza Stark Marked Region: ISCA-37432-Loss as ready
Renal Macrocystic Disease v0.109 ISCA-37432-Loss Zornitza Stark Region: isca-37432-loss has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 CYS1 Zornitza Stark Marked gene: CYS1 as ready
Renal Macrocystic Disease v0.109 CYS1 Zornitza Stark Gene: cys1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.109 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis-1, MIM#191100
Renal Macrocystic Disease v0.108 TSC1 Zornitza Stark Publications for gene: TSC1 were set to
Renal Macrocystic Disease v0.107 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v1.19 FOXI3 Zornitza Stark Phenotypes for gene: FOXI3 were changed from Dysostosis with predominant craniofacial involvement (MONDO:0800085) to Craniofacial microsomia 2, MIM# 620444
Mandibulofacial Acrofacial dysostosis v1.18 FOXI3 Zornitza Stark Publications for gene: FOXI3 were set to 36260083
Mandibulofacial Acrofacial dysostosis v1.17 FOXI3 Zornitza Stark reviewed gene: FOXI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37041148; Phenotypes: Craniofacial microsomia 2, MIM# 620444; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4608 FOXI3 Zornitza Stark Phenotypes for gene: FOXI3 were changed from Dysostosis with predominant craniofacial involvement (MONDO:0800085) to Craniofacial microsomia 2, MIM# 620444
Mendeliome v1.4607 FOXI3 Zornitza Stark Publications for gene: FOXI3 were set to 36260083
Mendeliome v1.4606 FOXI3 Zornitza Stark reviewed gene: FOXI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37041148; Phenotypes: Craniofacial microsomia 2, MIM# 620444; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v1.44 MARS2 Elena Tucker reviewed gene: MARS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cardiomyopathy_Paediatric v0.225 ALMS1 Chirag Patel Phenotypes for gene: ALMS1 were changed from OMIM 203800 to Cardiomyopathy, MONDO:0004994
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Marked gene: ALMS1 as ready
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Gene: alms1 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.63 ALMS1 Chirag Patel Phenotypes for gene: ALMS1 were changed from OMIM 203800 to Cardiomyopathy, MONDO:0004994
Dilated Cardiomyopathy v1.62 Chirag Patel Copied gene ALMS1 from panel Cardiomyopathy_Paediatric
Dilated Cardiomyopathy v1.62 ALMS1 Chirag Patel gene: ALMS1 was added
gene: ALMS1 was added to Dilated Cardiomyopathy. Sources: Expert Review Green,Expert Review,NHS GMS
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 15689433
Phenotypes for gene: ALMS1 were set to OMIM 203800
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel Marked gene: ALMS1 as ready
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel Gene: alms1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.224 ALMS1 Chirag Patel reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, MONDO:0004994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.710 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.4606 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.4605 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Ebstein-Bezieau neurodevelopmental syndrome, MIM# 621539, Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Deafness_IsolatedAndComplex v1.338 CLRN2 Bryony Thompson Publications for gene: CLRN2 were set to 33496845
Deafness_IsolatedAndComplex v1.337 CLRN2 Bryony Thompson Classified gene: CLRN2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.337 CLRN2 Bryony Thompson Gene: clrn2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.336 Bryony Thompson Added reviews for gene CLRN2 from panel Mendeliome
Mendeliome v1.4605 CLRN2 Bryony Thompson Publications for gene: CLRN2 were set to 33496845
Mendeliome v1.4604 CLRN2 Bryony Thompson Classified gene: CLRN2 as Green List (high evidence)
Mendeliome v1.4604 CLRN2 Bryony Thompson Gene: clrn2 has been classified as Green List (High Evidence).
Mendeliome v1.4603 CLRN2 Bryony Thompson reviewed gene: CLRN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39446282, 38243601, 33496845; Phenotypes: hearing loss, autosomal recessive 117, MONDO:0030905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.133 Bryony Thompson Copied gene CEP112 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.133 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 39349455; 31654588
Phenotypes for gene: CEP112 were set to Spermatogenic failure 44, MIM#619044; Acephalic spermatozoa; infertility
Mendeliome v1.4603 CEP112 Bryony Thompson Publications for gene: CEP112 were set to 31654588
Mendeliome v1.4602 CEP112 Bryony Thompson Deleted their comment
Mendeliome v1.4602 CEP112 Bryony Thompson edited their review of gene: CEP112: Added comment: PMIDs 31654588, 39349455 report a total of 4 unrelated families (4patients) with biallelic loss‑of‑function CEP112 variants causing male infertility phenotypes ranging from acephalic spermatozoa to oligoasthenoteratozoospermia and non‑obstructive azoospermia. Functional evidence includes loss of CEP112 protein in patient sperm, mouse Cep112 knockout infertility with ICSI rescue, and impaired phase‑separation of mutant proteins, supporting a diagnostic‑grade association of CEP112 with spermatogenic failure 44.; Changed publications: 39349455, 31654588; Changed phenotypes: spermatogenic failure 44, MONDO:0033622
Mendeliome v1.4602 CEP112 Bryony Thompson Classified gene: CEP112 as Green List (high evidence)
Mendeliome v1.4602 CEP112 Bryony Thompson Gene: cep112 has been classified as Green List (High Evidence).
Mendeliome v1.4601 CEP112 Bryony Thompson edited their review of gene: CEP112: Added comment: Now 4 unrelated biallelic male cases and a supporting mouse model.; Changed rating: GREEN; Changed publications: 31654588, 39349455; Changed phenotypes: spermatogenic failure MONDO:0004983
Mendeliome v1.4601 SLC30A5 Lucy Spencer reviewed gene: SLC30A5: Rating: AMBER; Mode of pathogenicity: None; Publications: 39790720; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4601 RUSC2 Lucy Spencer Phenotypes for gene: RUSC2 were changed from Mental retardation, autosomal recessive 61, MIM# 617773 to Intellectual developmental disorder, autosomal recessive 61 MIM#617773
Mendeliome v1.4600 RUSC2 Lucy Spencer Publications for gene: RUSC2 were set to 27612186
Mendeliome v1.4599 RUSC2 Lucy Spencer reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 36553572, 27612186; Phenotypes: Intellectual developmental disorder, autosomal recessive 61 MIM#617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Movement Disorders Superpanel v3.187 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Ataxia; Brain Channelopathies; Dystonia and Chorea; Paroxysmal Dyskinesia
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark Marked gene: TEX15 as ready
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark Gene: tex15 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.132 Zornitza Stark Copied gene TEX15 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.132 TEX15 Zornitza Stark gene: TEX15 was added
gene: TEX15 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TEX15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEX15 were set to 26199321; 28355598; 28303806
Phenotypes for gene: TEX15 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4599 RPL10L Lucy Spencer Phenotypes for gene: RPL10L were changed from MONDO_0004983, oligo-/azoospermia to Male infertility MONDO:0005372, RPL10L-related
Mendeliome v1.4598 RPL10L Lucy Spencer Publications for gene: RPL10L were set to PMID:32111475
Mendeliome v1.4597 RPL10L Lucy Spencer reviewed gene: RPL10L: Rating: AMBER; Mode of pathogenicity: None; Publications: 39625557; Phenotypes: Male infertility MONDO:0005372, RPL10L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.608 Sarah Milton Copied gene TNK2 from panel Mendeliome
Regression v0.608 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Regression. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4597 RNF212B Lucy Spencer Phenotypes for gene: RNF212B were changed from Infertility disorder, MONDO:0005047 to Infertility disorder, MONDO:0005047, RNF212B-related
Intellectual disability syndromic and non-syndromic v1.709 Sarah Milton Copied gene TNK2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.709 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4596 RNF212B Lucy Spencer Publications for gene: RNF212B were set to 37124137
Mendeliome v1.4595 RNF212B Lucy Spencer reviewed gene: RNF212B: Rating: AMBER; Mode of pathogenicity: None; Publications: 37124137, 40259604; Phenotypes: Infertility disorder, MONDO:0005047, RNF212B-related; Mode of inheritance: None
Genetic Epilepsy v1.389 Sarah Milton Added reviews for gene TNK2 from panel Mendeliome
Disorders of immune dysregulation v1.39 Sarah Milton Copied gene TNK2 from panel Mendeliome
Disorders of immune dysregulation v1.39 TNK2 Sarah Milton gene: TNK2 was added
gene: TNK2 was added to Disorders of immune dysregulation. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNK2 were set to 27977884; 23686771; 31517310
Phenotypes for gene: TNK2 were set to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome
Mendeliome v1.4595 TNK2 Sarah Milton changed review comment from: TNK2 encodes a cytosolic, nonreceptor tyrosine kinase that shows high expression in the brain.

Summary of literature on gene disease association thus far:

Mayer-Rokitansky-Kuster-Hauser syndrome
Single patient reported in PMID: 31517310, no functional studies

Neurodevelopmental disorder, MONDO:0700092
PMID: 39493104, 27977884, 23686771 - 4 families and 7 children affected with infantile onset epilepsy/spasms with associated regression. All had biallelic missense variants in TNK2. No functional studies thus far in regards to epilepsy phenotype.

SLE predisposition
1 family with 2 affected individuals with SLE with compound heterozygous variants in TNK2. Supportive functional studies showing missense variants detected resulted in loss of function, somewhat supportive mouse study.; to: TNK2 encodes a cytosolic, nonreceptor tyrosine kinase that shows high expression in the brain.

Summary of literature on gene disease association thus far:

Mayer-Rokitansky-Kuster-Hauser syndrome
Single patient reported in PMID: 31517310 with monoallelic TNK2 variant, no functional studies

Neurodevelopmental disorder, MONDO:0700092
PMID: 39493104, 27977884, 23686771 - 4 families and 7 children affected with infantile onset epilepsy/spasms with associated regression. All had biallelic missense variants in TNK2. No functional studies thus far in regards to epilepsy phenotype.

SLE predisposition
PMID: 38883731 - 1 family with 2 affected individuals with SLE with compound heterozygous missense variants in TNK2. Supportive functional studies showing missense variants detected resulted in loss of function, somewhat supportive mouse study.
Mendeliome v1.4595 TNK2 Sarah Milton reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 39570652, 39493104, 31517310, 27977884, 23686771; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, Mayer-Rokitansky-Kuster-Hauser syndrome MONDO:0017771, Lupus erythematosus MONDO:0004670; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4595 RIPOR2 Lucy Spencer Publications for gene: RIPOR2 were set to 24958875; 32631815
Mendeliome v1.4594 RIPOR2 Lucy Spencer reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37164627; Phenotypes: Deafness, autosomal dominant 21, MIM#607017; Mode of inheritance: None
Mendeliome v1.4594 RHOB Lucy Spencer Phenotypes for gene: RHOB were changed from Cerebral Palsy to Cerebral palsy MONDO:0006497, RHOB-related
Mendeliome v1.4593 RHOB Lucy Spencer Publications for gene: RHOB were set to 32989326
Mendeliome v1.4592 RHOB Lucy Spencer edited their review of gene: RHOB: Added comment: PMID: 32989326 2 CP patients de novo for the same missense S73F, absent from gnomad

PMID: 39080495 no new patients, created a KI rabbit model of S73F which showed CP symptoms ie periventricular leukomalacia and spastic-dystonic diplegia. Also showed the variant activates ACAT1 altering lipid levels which may lead to neuronal and white matter damage resulting in CP.

Still only 2 patients with the same variant reported - amber; Changed rating: AMBER; Changed publications: 32989326, 39080495; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Red cell disorders v1.48 EPAS1 Zornitza Stark Phenotypes for gene: EPAS1 were changed from Erythrocytosis, familial, 4, MIM# 611783 to Erythrocytosis, familial, 4, MIM# 611783; Hereditary anaemia, MONDO:0016624, EPAS1-related
Red cell disorders v1.47 EPAS1 Zornitza Stark Publications for gene: EPAS1 were set to 18184961; 18378852; 22367913; 18650473
Red cell disorders v1.46 EPAS1 Zornitza Stark edited their review of gene: EPAS1: Added comment: PMID 39613395: reports 3 individuals from 3 unrelated families with heterozygous EPAS1 loss-of-function variants (two de novo frameshifts, one maternally inherited missense) presenting with childhood-onset congenital hypoplastic anaemia characterized by normocytic normochromic anaemia, reticulocytopenia and relative EPO deficiency; additional cardiac and neurological features in some patients. In‑vitro functional assays (Western blot, immunofluorescence, co‑IP, luciferase reporter, qPCR) demonstrate reduced protein abundance, impaired nuclear localisation, defective CBP binding and decreased EPO transcription, supporting pathogenicity.; Changed publications: 18184961, 18378852, 22367913, 18650473, 39613395; Changed phenotypes: Erythrocytosis, familial, 4, MIM# 611783, Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4592 EPAS1 Zornitza Stark Phenotypes for gene: EPAS1 were changed from Familial erythrocytosis (MIM#611783), AD to Familial erythrocytosis (MIM#611783); Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4591 EPAS1 Zornitza Stark Publications for gene: EPAS1 were set to 27292716; 19208626
Mendeliome v1.4590 EPAS1 Zornitza Stark edited their review of gene: EPAS1: Changed phenotypes: Hereditary anaemia, MONDO:0016624, EPAS1-related
Mendeliome v1.4590 EPAS1 Zornitza Stark reviewed gene: EPAS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39613395; Phenotypes: Hereditary anemia, MONDO:0016624, EPAS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4590 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to 25512093; 28196890; 21820100; 32788638; 27549087
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228, Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563, Spinal muscular atrophy, lower extremity-predominant 1, MIM# 158600
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228, Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: dyneinopathy MONDO:1040031, Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228
Mendeliome v1.4589 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Added comment: PMID 38848546 reports 47 individuals from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years). Most individuals presented with divergent neurological and multisystem features such as autonomic features, behavioural disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. Age-dependent biphasic disease course observed with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, in several cases neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health.; Changed publications: 21820100, 32788638, 27549087, 38848546
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Marked gene: DDX41 as ready
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Classified gene: DDX41 as Green List (high evidence)
Syndromic Retinopathy v0.251 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.250 DDX41 Zornitza Stark gene: DDX41 was added
gene: DDX41 was added to Syndromic Retinopathy. Sources: Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Review for gene: DDX41 was set to GREEN
Added comment: This study reports 13 individuals from nine unrelated families with biallelic DDX41 variants (missense, frameshift and splice‑affecting) presenting with Leber congenital amaurosis / early‑onset severe retinal dystrophy, often accompanied by neurodevelopmental and skeletal anomalies. The variants are ultra‑rare, segregate in an autosomal recessive pattern, and lead to reduced DDX41 protein levels in patient fibroblasts and in a knock‑in mouse retina, with early ERG deficits and progressive photoreceptor loss. Biochemical assays demonstrate impaired RNA binding and protein instability, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
IBMDx study v0.42 DDX41 Zornitza Stark Marked gene: DDX41 as ready
IBMDx study v0.42 DDX41 Zornitza Stark Gene: ddx41 has been classified as Green List (High Evidence).
IBMDx study v0.42 DDX41 Zornitza Stark Mode of inheritance for gene: DDX41 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.185 Chirag Patel Copied gene NRP1 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.185 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Mendeliome v1.4589 Chirag Patel Copied gene NRP1 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4589 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel Marked gene: NRP1 as ready
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel Gene: nrp1 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.87 NRP1 Chirag Patel gene: NRP1 was added
gene: NRP1 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NRP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP1 were set to 34636164; 28334861
Phenotypes for gene: NRP1 were set to Hypogonadotropic hypogonadism MONDO:0018555
Review for gene: NRP1 was set to RED
Added comment: PMID 28334861 and PMID 34636164 report a total of 13 individuals (8 families, 8 unrelated) with heterozygous missense NRP1 variants presenting with isolated hypogonadotropic hypogonadism / Kallmann syndrome (childhood‑adolescent onset, anosmia, low gonadotropins). Several variants inherited from unaffected parents. No functional assays were performed, but the variants are rare and predicted loss‑of‑function. Variants are classified as VUS. Oligogenic inheritance in some probands with additional IHH‑associated gene variants.
Sources: Literature
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel Marked gene: NRP2 as ready
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4588 NRP2 Chirag Patel Marked gene: NRP2 as ready
Mendeliome v1.4588 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4588 Chirag Patel Copied gene NRP2 from panel Hypogonadotropic hypogonadism
Mendeliome v1.4588 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Pituitary hormone deficiency v0.184 Chirag Patel Copied gene NRP2 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.184 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Marked gene: NRP2 as ready
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Gene: nrp2 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel reviewed gene: NRP2: Rating: RED; Mode of pathogenicity: None; Publications: 34636164, 28334861; Phenotypes: Hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel Deleted their review
Hypogonadotropic hypogonadism v0.86 NRP2 Chirag Patel gene: NRP2 was added
gene: NRP2 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: NRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NRP2 were set to 34636164; 28334861
Phenotypes for gene: NRP2 were set to Hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: NRP2 was set to GREEN
Added comment: PMID 28334861 reports four individuals with heterozygous NRP2 missense variants presenting with Kallmann syndrome (congenital hypogonadotropic hypogonadism with anosmia). PMID 34636164 reports two unrelated families with heterozygous NRP2 missense variants causing isolated normosmic hypogonadotropic hypogonadism. No functional validation or segregation data were provided for any variant. Variants are too common in population and/or classified as VUS/benign.
Sources: Literature
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel Marked gene: PLXNA1 as ready
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel Marked gene: PLXNA1 as ready
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.183 Chirag Patel Copied gene PLXNA1 from panel Differences of Sex Development
Pituitary hormone deficiency v0.183 PLXNA1 Chirag Patel gene: PLXNA1 was added
gene: PLXNA1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNA1 were set to 28334861; 30467832; 34636164
Phenotypes for gene: PLXNA1 were set to Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Hypogonadotropic hypogonadism v0.85 Chirag Patel Copied gene PLXNA1 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.85 PLXNA1 Chirag Patel gene: PLXNA1 was added
gene: PLXNA1 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PLXNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLXNA1 were set to 28334861; 30467832; 34636164
Phenotypes for gene: PLXNA1 were set to Hypogonadotropic hypogonadism MONDO:0018555, PLXNA1-related
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel Marked gene: TTC26 as ready
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel Gene: ttc26 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.53 Chirag Patel Copied gene TTC26 from panel Ciliopathies
Renal Ciliopathies and Nephronophthisis v1.53 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903
Phenotypes for gene: TTC26 were set to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel Marked gene: TTC26 as ready
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel Gene: ttc26 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.182 Chirag Patel Copied gene TTC26 from panel Hypogonadotropic hypogonadism
Pituitary hormone deficiency v0.182 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Pituitary hormone deficiency. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 32617964
Phenotypes for gene: TTC26 were set to biliary, renal, neurologic, and skeletal syndrome, MONDO:0859191
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel Marked gene: TTC26 as ready
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel Gene: ttc26 has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v0.84 TTC26 Chirag Patel gene: TTC26 was added
gene: TTC26 was added to Hypogonadotropic hypogonadism. Sources: Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 32617964
Phenotypes for gene: TTC26 were set to biliary, renal, neurologic, and skeletal syndrome, MONDO:0859191
Review for gene: TTC26 was set to RED
Added comment: PMID 32617964 reports 4 individuals from 2 unrelated consanguineous families with the same homozygous TTC26 variant (c.695A>G, p.Asn232Ser) presenting with pituitary stalk interruption syndrome (PSIS) and multiple anterior pituitary hormone deficiencies (GH, ACTH, TSH), micropenis, growth failure, and additional hepatic, renal, cardiac and skeletal anomalies. The phenotype also includes features of hypogonadotropic hypogonadism (micropenis). No functional validation of the missense variant is provided.
Sources: Literature
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel Marked gene: AKT3 as ready
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel Gene: akt3 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.181 AKT3 Chirag Patel gene: AKT3 was added
gene: AKT3 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AKT3 were set to 38459620; 28190287
Phenotypes for gene: AKT3 were set to overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Review for gene: AKT3 was set to RED
Added comment: ClinGen DEFINITIVE association (Jul 2021) with GOF mechanism and only missense variants reported.

PMID 35665751 reports 1 individual with a de novo AKT3 p.Gln78Arg gain‑of‑function variant causing congenital hypothyroidism (thyroid hypogenesis), megalencephaly and polymicrogyria. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth hormone deficiency and central hypothyroidism.


PMID 28190287 reports 1 individual with a de novo AKT3 p.Glu40Lys gain‑of‑function variant causing childhood‑onset megalencephaly, hypotonia, connective‑tissue laxity and growth‑hormone deficiency. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth‑hormone deficiency and central hypothyroidism.
Sources: Literature
Congenital hypothyroidism v0.91 AKT3 Chirag Patel Marked gene: AKT3 as ready
Congenital hypothyroidism v0.91 AKT3 Chirag Patel Gene: akt3 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.91 AKT3 Chirag Patel gene: AKT3 was added
gene: AKT3 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AKT3 were set to 38459620; 35665751
Phenotypes for gene: AKT3 were set to overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Review for gene: AKT3 was set to RED
Added comment: ClinGen DEFINITIVE association (Jul 2021) with GOF mechanism and only missense variants reported.

PMID 35665751 reports 1 individual with a de novo AKT3 p.Gln78Arg gain‑of‑function variant causing congenital hypothyroidism (thyroid hypogenesis), megalencephaly and polymicrogyria. PMID 38459620 reports 1 individual with a AKT3 p.Asp322Tyr gain‑of‑function variant causing megalencephaly, growth hormone deficiency and central hypothyroidism.
Sources: Literature
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel Marked gene: HIST1H1E as ready
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel Gene: hist1h1e has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.90 HIST1H1E Chirag Patel gene: HIST1H1E was added
gene: HIST1H1E was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: HIST1H1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H1E were set to 40444808; 34290007
Phenotypes for gene: HIST1H1E were set to Rahman syndrome, MIM# 617537
Review for gene: HIST1H1E was set to RED
Added comment: Rahman syndrome is characterized by mild to severe intellectual disability associated with variable somatic overgrowth. Some individuals may have other minor anomalies, including dysmorphic facial features, strabismus, or camptodactyly. More than 40 unrelated individuals reported. PTVs result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain.

PMID 34290007 and 40444808 report 2 unrelated individuals with Rahman syndrome with central hypothyroidism.
Sources: Literature
Adrenal insufficiency v0.76 KCNQ1 Chirag Patel edited their review of gene: KCNQ1: Added comment: Additional 1 individual with a rare heterozygous missense KCNQ1 variant (p.P369L) presenting with childhood‑onset central hypothyroidism as part of multiple pituitary hormone deficiency (GH, ACTH, TSH, hypogonadotropic hypogonadism), gingival fibromatosis, dysmorphic facial features, and short stature. The variant was inherited from his unaffected mother.; Changed rating: GREEN; Changed publications: 38987191; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adrenal insufficiency v0.76 KCNQ1 Chirag Patel Phenotypes for gene: KCNQ1 were changed from Hypopituitarism, MONDO:0005152; Long QT syndrome 1 (192500) to Hypopituitarism, MONDO:0005152
Adrenal insufficiency v0.75 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Pituitary hormone deficiency v0.180 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Congenital hypothyroidism v0.89 KCNQ1 Chirag Patel Publications for gene: KCNQ1 were set to 29097701
Adrenal insufficiency v0.74 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Green List (high evidence)
Adrenal insufficiency v0.74 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.73 Chirag Patel Added reviews for gene KCNQ1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel Marked gene: KCNQ1 as ready
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.88 Chirag Patel Copied gene KCNQ1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.88 KCNQ1 Chirag Patel gene: KCNQ1 was added
gene: KCNQ1 was added to Congenital hypothyroidism. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNQ1 were set to 29097701
Phenotypes for gene: KCNQ1 were set to Hypopituitarism, MONDO:0005152
Adrenal insufficiency v0.72 Chirag Patel Added reviews for gene KCNQ1 from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.179 KCNQ1 Chirag Patel Phenotypes for gene: KCNQ1 were changed from Hypopituitarism, MONDO:0005152; Long QT syndrome 1 (192500) to Hypopituitarism, MONDO:0005152
Pituitary hormone deficiency v0.178 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Green List (high evidence)
Pituitary hormone deficiency v0.178 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.177 KCNQ1 Chirag Patel edited their review of gene: KCNQ1: Added comment: Additional 1 individual with a rare heterozygous missense KCNQ1 variant (p.P369L) presenting with childhood‑onset central hypothyroidism as part of multiple pituitary hormone deficiency (GH, ACTH, TSH, hypogonadotropic hypogonadism), gingival fibromatosis, dysmorphic facial features, and short stature. The variant was inherited from his unaffected mother.; Changed rating: GREEN; Changed publications: 38987191
Mendeliome v1.4587 Chirag Patel Added reviews for gene MAMLD1 from panel Congenital hypothyroidism
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel Marked gene: MAMLD1 as ready
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel Gene: mamld1 has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.87 MAMLD1 Chirag Patel gene: MAMLD1 was added
gene: MAMLD1 was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: MAMLD1 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: MAMLD1 were set to 36898841
Phenotypes for gene: MAMLD1 were set to Congenital hypothyroidism MONDO:0018612
Review for gene: MAMLD1 was set to RED
Added comment: PMID 36898841 reports 2 individuals from 2 unrelated South East Asian families with hemizygous X‑linked MAMLD1 variants presenting with congenital hypothyroidism due to dyshormonogenesis. Both patients have early‑onset hypothyroidism (30 days and 15 years). Functional assays show gain‑of‑function effects on non‑canonical Notch signalling, increasing HES3 expression and suppressing HES1‑dependent thyroid hormone biosynthesis genes.

However, the non‑frameshift duplication p.Q477dup was maternally inherited and has a relatively high allele frequency in East Asian populations (0.54 %), and the in silico predictions for the de novo missense p.C942Y variant are benign.
Sources: Literature
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Marked gene: OTUD6B as ready
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Gene: otud6b has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Classified gene: OTUD6B as Red List (low evidence)
Congenital hypothyroidism v0.86 OTUD6B Chirag Patel Gene: otud6b has been classified as Red List (Low Evidence).
Congenital hypothyroidism v0.85 OTUD6B Chirag Patel reviewed gene: OTUD6B: Rating: RED; Mode of pathogenicity: None; Publications: 41188742, 32924626; Phenotypes: Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v0.85 Chirag Patel Copied gene OTUD6B from panel Mendeliome
Congenital hypothyroidism v0.85 OTUD6B Chirag Patel gene: OTUD6B was added
gene: OTUD6B was added to Congenital hypothyroidism. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OTUD6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD6B were set to 28343629; 32924626; 31147255
Phenotypes for gene: OTUD6B were set to Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel Marked gene: SOX11 as ready
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel Gene: sox11 has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism v0.83 Chirag Patel Copied gene SOX11 from panel Differences of Sex Development
Hypogonadotropic hypogonadism v0.83 SOX11 Chirag Patel gene: SOX11 was added
gene: SOX11 was added to Hypogonadotropic hypogonadism. Sources: Expert Review Green,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
Adrenal insufficiency v0.71 TBCE Chirag Patel Marked gene: TBCE as ready
Adrenal insufficiency v0.71 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Adrenal insufficiency v0.71 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Adrenal insufficiency v0.71 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Adrenal insufficiency v0.70 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 39086450
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: PMID 33150438 describes a cohort of 63 patients with HRD syndrome, 62 of whom harbor the same homozygous c.155_166del12 deletion and one with homozygous c.207_208delTA. Adrenal glucocorticoid insufficiency was diagnosed in 22% of patients.
Sources: Literature
Congenital hypothyroidism v0.84 TBCE Chirag Patel Marked gene: TBCE as ready
Congenital hypothyroidism v0.84 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.84 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Congenital hypothyroidism v0.84 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.83 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Congenital hypothyroidism. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 39086450; 33150438; 26336027
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: PMID 33150438 describes a cohort of 63 patients with HRD syndrome, 62 of whom harbor the same homozygous c.155_166del12 deletion and one with homozygous c.207_208delTA. Hypothyroidism was found in 36% of patients.

PMID 26336027 reports a Moroccan child with HRD syndrome and congenital hypothyroidism with the homozygous c.155_166del12 deletion.

PMID 39086450 reports a Libyan child with HRD syndrome and congenital hypothyroidism with the homozygous c.155_166del12 deletion.
Sources: Literature
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Marked gene: C14orf80 as ready
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Gene: c14orf80 has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Classified gene: C14orf80 as Red List (low evidence)
Adrenal insufficiency v0.69 C14orf80 Chirag Patel Gene: c14orf80 has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.68 C14orf80 Chirag Patel gene: C14orf80 was added
gene: C14orf80 was added to Adrenal insufficiency. Sources: Literature
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 Syndromic disease, MONDO:0002254
Review for gene: C14orf80 was set to RED
Added comment: Adrenal insufficiency only reported in 2 male siblings from 1 non-consanguineous family with biallelic loss‑of‑function TEDC1 variants (c.104-5C>G and p.Ala263LeufsTer29). They also had prenatal‑onset severe growth impairment, primary microcephaly, primary hypogonadism, congenital glaucoma, craniosynostosis, tracheal stenosis and developmental delay. Functional studies demonstrate loss of TEDC1 protein, disrupted TEDC2 binding, cell‑cycle defects in patient lymphoblastoid cells, and recapitulation of growth and cranial phenotypes in a tedc1‑/‑ zebrafish model.

Total of 5 individuals from 3 families reported with biallelic loss‑of‑function TEDC1 variants, presenting with developmental delay and microcephaly.
Sources: Literature
Adrenal insufficiency v0.67 CPOX Chirag Patel Marked gene: CPOX as ready
Adrenal insufficiency v0.67 CPOX Chirag Patel Gene: cpox has been classified as Green List (High Evidence).
Adrenal insufficiency v0.67 CPOX Chirag Patel Classified gene: CPOX as Green List (high evidence)
Adrenal insufficiency v0.67 CPOX Chirag Patel Gene: cpox has been classified as Green List (High Evidence).
Adrenal insufficiency v0.66 CPOX Chirag Patel gene: CPOX was added
gene: CPOX was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: CPOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPOX were set to 40857591; 40481674; 40296768
Phenotypes for gene: CPOX were set to harderoporphyria, MONDO:0030048
Review for gene: CPOX was set to GREEN
Added comment: ClinGen DEFINITIVE association (Jan 2023).

Childhood‑onset primary adrenal insufficiency reported in 5 individuals from 4 unrelated families with biallelic loss‑of‑function CPOX variants, with 3 individuals also having 46,XY DSD (PMID 40296768 and 40481674).
Sources: Literature
Syndromic Retinopathy v0.249 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Syndromic Retinopathy v0.249 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Syndromic Retinopathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Microcephaly v1.421 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Microcephaly v1.421 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Microcephaly. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Fetal anomalies v1.544 Sarah Milton Copied gene TOMM7 from panel Mendeliome
Fetal anomalies v1.544 TOMM7 Sarah Milton gene: TOMM7 was added
gene: TOMM7 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36299998; 36282599
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, MIM# 620601
Mendeliome v1.4586 TOMM7 Sarah Milton reviewed gene: TOMM7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39615461, 36299998, 36282599; Phenotypes: Garg-Mishra progeroid syndrome, MIM#620601; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adrenal insufficiency v0.65 GFER Chirag Patel Marked gene: GFER as ready
Adrenal insufficiency v0.65 GFER Chirag Patel Gene: gfer has been classified as Red List (Low Evidence).
Adrenal insufficiency v0.65 GFER Chirag Patel gene: GFER was added
gene: GFER was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 26018198
Phenotypes for gene: GFER were set to Mitochondrial disease, MONDO:0044970
Review for gene: GFER was set to RED
Added comment: ClinGen DEFINITIVE association with disease (Sep'23).
Only 1 patient aged 19 years reported with infancy onset adrenal insufficiency.
Sources: Literature
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Marked gene: HSD17B4 as ready
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Gene: hsd17b4 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Classified gene: HSD17B4 as Green List (high evidence)
Adrenal insufficiency v0.64 HSD17B4 Chirag Patel Gene: hsd17b4 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.63 HSD17B4 Chirag Patel gene: HSD17B4 was added
gene: HSD17B4 was added to Adrenal insufficiency. Sources: Literature,ClinGen
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD17B4 were set to 40416444; 32904102; 32528852
Phenotypes for gene: HSD17B4 were set to d-bifunctional protein deficiency, MONDO:0009855
Review for gene: HSD17B4 was set to GREEN
Added comment: ClinGen DEFINITIVE association with disease (Apr 2020).

Adrenal insufficiency reported in 5 individuals from 3 unrelated families with D‑bifunctional protein deficiency due to biallelic loss‑of‑function HSD17B4 variants.
Sources: Literature, ClinGen
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel Marked gene: MAGEL2 as ready
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel Gene: magel2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.177 Chirag Patel Copied gene MAGEL2 from panel Mendeliome
Pituitary hormone deficiency v0.177 MAGEL2 Chirag Patel gene: MAGEL2 was added
gene: MAGEL2 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: MAGEL2 were set to 33820833; 24076603; 31397880; 29599419; 30302899
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, MIM# 615547
Mendeliome v1.4586 KLHL15 Sangavi Sivagnanasundram changed review comment from: A 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; to: 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
Mendeliome v1.4586 KLHL15 Sangavi Sivagnanasundram reviewed gene: KLHL15: Rating: GREEN; Mode of pathogenicity: None; Publications: 37452054; Phenotypes: intellectual disability, X-linked 103 MONDO:0010508; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Adrenal insufficiency v0.62 FOXA2 Chirag Patel Marked gene: FOXA2 as ready
Adrenal insufficiency v0.62 FOXA2 Chirag Patel Gene: foxa2 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.62 PROP1 Chirag Patel Marked gene: PROP1 as ready
Adrenal insufficiency v0.62 PROP1 Chirag Patel Gene: prop1 has been classified as Green List (High Evidence).
Adrenal insufficiency v0.62 PROP1 Chirag Patel changed review comment from: Well-established gene-disease association; Over 30 unrelated families with homozygous/ compound heterozygous (small deletions, frameshift, insertions, missense, nonsense and splice) PROP1 variants. The majority of patients present with complete absence of puberty, dwarfism and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland. Most affected individuals are ascertained due to growth failure (early childhood) and failure to thrive starting in infancy.; to: Well-established gene-disease association; Over 30 unrelated families with homozygous/ compound heterozygous (small deletions, frameshift, insertions, missense, nonsense and splice) PROP1 variants. The majority of patients present with complete absence of puberty, dwarfism and low GH, PRL, TSH, LH, and FSH associated with severe hypoplasia of the pituitary gland. Most affected individuals are ascertained due to growth failure (early childhood) and failure to thrive starting in infancy.

10 individuals developed progressive ACTH deficiency around mid 20s.
Adrenal insufficiency v0.62 Chirag Patel Copied gene PROP1 from panel Pituitary hormone deficiency
Adrenal insufficiency v0.62 PROP1 Chirag Patel gene: PROP1 was added
gene: PROP1 was added to Adrenal insufficiency. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROP1 were set to 20301521, 31090814
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2 MIM# 262600
Adrenal insufficiency v0.61 Chirag Patel Copied gene FOXA2 from panel Pituitary hormone deficiency
Adrenal insufficiency v0.61 FOXA2 Chirag Patel gene: FOXA2 was added
gene: FOXA2 was added to Adrenal insufficiency. 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
Adrenal insufficiency v0.60 IARS2 Chirag Patel Marked gene: IARS2 as ready
Adrenal insufficiency v0.60 IARS2 Chirag Patel Gene: iars2 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.60 IARS2 Chirag Patel Classified gene: IARS2 as Amber List (moderate evidence)
Adrenal insufficiency v0.60 IARS2 Chirag Patel Gene: iars2 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.59 IARS2 Chirag Patel gene: IARS2 was added
gene: IARS2 was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to 30419932
Phenotypes for gene: IARS2 were set to cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, MONDO:0014455
Review for gene: IARS2 was set to AMBER
Added comment: Established gene-disease association with cataract‑growth hormone deficiency‑sensory neuropathy‑sensorineural hearing loss‑skeletal dysplasia (CAGSSS) syndrome.

PMID 30419932 reports 2 unrelated individuals with the same homozygous missense variant in IARS2 gene (p.Pro909Ser) presenting with CAGSSS syndrome and central adrenal insufficiency.
Sources: Literature
Mendeliome v1.4586 POU3F4 upstream regulatory region Sarah Milton Region: POU3F4 upstream regulatory region was added
Region: POU3F4 upstream regulatory region was added to Mendeliome. Sources: Literature
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
Review for Region: POU3F4 upstream regulatory region was set to AMBER
Added comment: 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
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.204 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Marked gene: WNT4 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Classified gene: WNT4 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.203 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4585 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.202 Chirag Patel Added reviews for gene WNT4 from panel Adrenal insufficiency
Adrenal insufficiency v0.58 WNT4 Chirag Patel Classified gene: WNT4 as Amber List (moderate evidence)
Adrenal insufficiency v0.58 WNT4 Chirag Patel Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Adrenal insufficiency v0.57 WNT4 Chirag Patel edited their review of gene: WNT4: Added comment: A male fetus from consanguineous family with features of SERKAL syndrome (bilateral diaphragma genesis, pulmonary hypoplasia, bilateral renal hypoplasia with cystic dysplasia, RT adrenal agenesis, LT adrenal hypoplasia), and a homozygous missense variant in WNT4 gene (T291R) with parents as heterozygous carriers. Wnt4 -/- mice had ventricular septal defects, small/absent kidneys, sac hernias of diaphragm, and cleft soft palate.; Changed rating: AMBER; Changed publications: 40992710
Mendeliome v1.4584 KIF3B Sangavi Sivagnanasundram changed review comment from: Addtional publication to support review from 2020
"2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking."

GDA to remain as AMBER; to: Addition of publication to support review from 2020
"2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking."

GDA to remain as AMBER
Mendeliome v1.4584 KIF3B Sangavi Sivagnanasundram reviewed gene: KIF3B: Rating: AMBER; Mode of pathogenicity: None; Publications: 34455394; Phenotypes: ciliopathy MONDO:0005308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.248 TRANK1 Chirag Patel Marked gene: TRANK1 as ready
Autism v0.248 TRANK1 Chirag Patel Gene: trank1 has been classified as Red List (Low Evidence).
Autism v0.248 Chirag Patel Copied gene TRANK1 from panel Mendeliome
Autism v0.248 TRANK1 Chirag Patel gene: TRANK1 was added
gene: TRANK1 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TRANK1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRANK1 were set to 38649688; 30504930
Phenotypes for gene: TRANK1 were set to Autism, MONDO:0005260
Mendeliome v1.4584 TRANK1 Chirag Patel Marked gene: TRANK1 as ready
Mendeliome v1.4584 TRANK1 Chirag Patel Gene: trank1 has been classified as Red List (Low Evidence).
Mendeliome v1.4584 TRANK1 Chirag Patel gene: TRANK1 was added
gene: TRANK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRANK1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRANK1 were set to 38649688; 30504930
Phenotypes for gene: TRANK1 were set to Autism, MONDO:0005260
Review for gene: TRANK1 was set to RED
Added comment: PMID 30504930 describes 2 unrelated individuals with de novo TRANK1 missense variants (p.Val901Ile and p.Thr2109Lys) and autism spectrum disorder (ASD). No functional studies.

PMID 38649688 identifies 2 brothers from a consanguineous family with a homozygous TRANK1 missense variant (p.Glu273Gly) presenting with ASD, non‑verbal status and associated behavioural traits. Parents heterozygous carriers with no phenotype. No functional studies.
Sources: Literature
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel Marked gene: GLTP as ready
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Ichthyosis and Porokeratosis v1.25 Chirag Patel Copied gene GLTP from panel Mendeliome
Ichthyosis and Porokeratosis v1.25 GLTP Chirag Patel gene: GLTP was added
gene: GLTP was added to Ichthyosis and Porokeratosis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: GLTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLTP were set to 41642656
Phenotypes for gene: GLTP were set to Ichthyosis, MONDO:0019269; Epidermal differentiation disorder
Mendeliome v1.4583 GLTP Chirag Patel Marked gene: GLTP as ready
Mendeliome v1.4583 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Mendeliome v1.4583 GLTP Chirag Patel Classified gene: GLTP as Green List (high evidence)
Mendeliome v1.4583 GLTP Chirag Patel Gene: gltp has been classified as Green List (High Evidence).
Mendeliome v1.4582 GLTP Chirag Patel gene: GLTP was added
gene: GLTP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GLTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLTP were set to 41642656
Phenotypes for gene: GLTP were set to Ichthyosis, MONDO:0019269; Epidermal differentiation disorder
Review for gene: GLTP was set to GREEN
Added comment: PMID 41642656 reports 6 individuals from 5 unrelated families with rare biallelic loss‑of‑function GLTP variants (c.58_62del, c.98delT, c.162+2T>C). Individuals presented with non-syndromic epidermal differentiation disorder (generalized scaling, hyperkeratosis, and pruritus from birth, without extra‑dermal anomalies). GLTP encodes a glycolipid transfer protein that mediates inter‑membrane transport of glucosylceramide. The variants segregated with disease. Functional studies (CRISPR mouse knockout, keratinocyte knockdown, and rescue by eliglustat) demonstrate loss of GLTP expression and disrupted GlcCer trafficking, supporting a loss‑of‑function disease mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.708 Sarah Milton Added reviews for gene KDM5B from panel Mendeliome
Autism v0.247 Sarah Milton Added reviews for gene KDM5B from panel Mendeliome
Mendeliome v1.4581 KDM5B Sarah Milton reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37231097; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KDM5B-related, Intellectual developmental disorder, autosomal recessive 65 (MIM#618109); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Ataxia v1.195 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Ataxia v1.195 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v1.149 Chirag Patel Copied gene CD99L2 from panel Mendeliome
Hereditary Spastic Paraplegia v1.149 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Hereditary Spastic Paraplegia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Ataxia v1.195 Chirag Patel Copied gene CD99L2 from panel Mendeliome
Ataxia v1.195 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Ataxia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Mendeliome v1.4581 CD99L2 Chirag Patel Phenotypes for gene: CD99L2 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092; CD99L2-related
Mendeliome v1.4580 CD99L2 Chirag Patel Marked gene: CD99L2 as ready
Mendeliome v1.4580 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Marked gene: PDS5A as ready
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Tag preprint tag was added to gene: PDS5A.
Mendeliome v1.4580 CD99L2 Chirag Patel Classified gene: CD99L2 as Green List (high evidence)
Mendeliome v1.4580 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.707 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4579 CD99L2 Chirag Patel Classified gene: CD99L2 as Green List (high evidence)
Mendeliome v1.4579 CD99L2 Chirag Patel Gene: cd99l2 has been classified as Green List (High Evidence).
Mendeliome v1.4578 PDS5A Chirag Patel Classified gene: PDS5A as Amber List (moderate evidence)
Mendeliome v1.4578 PDS5A Chirag Patel Gene: pds5a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.706 PDS5B Chirag Patel Classified gene: PDS5B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.706 PDS5B Chirag Patel Gene: pds5b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4577 PDS5A Chirag Patel Tag preprint tag was added to gene: PDS5A.
Intellectual disability syndromic and non-syndromic v1.705 PDS5B Chirag Patel Tag preprint tag was added to gene: PDS5B.
Mendeliome v1.4577 PDS5B Chirag Patel Tag preprint tag was added to gene: PDS5B.
Mendeliome v1.4577 PDS5B Chirag Patel Classified gene: PDS5B as Amber List (moderate evidence)
Mendeliome v1.4577 PDS5B Chirag Patel Gene: pds5b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4576 CD99L2 Chirag Patel gene: CD99L2 was added
gene: CD99L2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CD99L2 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: CD99L2 were set to 41690933
Phenotypes for gene: CD99L2 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CD99L2 was set to GREEN
Added comment: PMID 41690933 identified loss‑of‑function variants in CD99L2 gene in 25 males from 20 unrelated families with X-linked spastic ataxia. The age of onset ranged from 10-68yrs, and the main presenting features were gait disturbances and spasticity (mostly lower limbs), ataxia, dysarthria, oculomotor abnormalities, sensory deficits, and dysphagia. Only 2/19 individuals had cerebellar atrophy on MRI brain. Only 1/4 female carriers had any clinical features.

RNA‑seq showed reduced CD99L2 transcripts and western blot demonstrated loss of full‑length protein. Loss of CD99L2 in patients’ fibroblasts triggered transcriptional dysregulation of genes linked to neuronal and synaptic function. Ablation of cytoplasmic or extracellular domains of CD99L2 lead to its intracellular mislocalisation and abrogation of its interplay with CAPN1 (a calcium-dependent cysteine protease involved in neuronal plasticity).
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.705 Chirag Patel Copied gene PDS5B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.705 PDS5B Chirag Patel gene: PDS5B was added
gene: PDS5B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PDS5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Phenotypes for gene: PDS5B were set to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability syndromic and non-syndromic v1.705 Chirag Patel Copied gene PDS5A from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.705 PDS5A Chirag Patel gene: PDS5A was added
gene: PDS5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PDS5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: PDS5A were set to Complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4575 PDS5A Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel changed review comment from: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature; to: Boone 2026 reports 8 individuals from 8 unrelated families with rare heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Mendeliome v1.4575 PDS5B Chirag Patel Classified gene: PDS5B as Green List (high evidence)
Mendeliome v1.4575 PDS5B Chirag Patel Gene: pds5b has been classified as Green List (High Evidence).
Mendeliome v1.4574 PDS5B Chirag Patel Marked gene: PDS5B as ready
Mendeliome v1.4574 PDS5B Chirag Patel Gene: pds5b has been classified as Red List (Low Evidence).
Mendeliome v1.4574 PDS5B Chirag Patel gene: PDS5B was added
gene: PDS5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDS5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5B were set to 10.64898/2026.02.23.26346364
Phenotypes for gene: PDS5B were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: PDS5B was set to GREEN
Added comment: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous loss of function PDS5B variants and variable neurodevelopmental features. Inheritance of variants was 4 de novo, 3 unknown, and 1 inherited from unaffected parent. No functional studies were presented.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel Marked gene: FMO4 as ready
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel Gene: fmo4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.704 Chirag Patel Copied gene FMO4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.704 FMO4 Chirag Patel gene: FMO4 was added
gene: FMO4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: FMO4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FMO4 were set to 41714691, 28940097
Phenotypes for gene: FMO4 were set to Neurodevelopmental disorder, MONDO:0700092; FMO4 related
Mendeliome v1.4573 Chirag Patel Added reviews for gene PDS5A from panel Mendeliome
Mendeliome v1.4572 PDS5A Chirag Patel Marked gene: PDS5A as ready
Mendeliome v1.4572 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v1.4572 PDS5A Chirag Patel Classified gene: PDS5A as Green List (high evidence)
Mendeliome v1.4572 PDS5A Chirag Patel Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v1.4571 PDS5A Chirag Patel gene: PDS5A was added
gene: PDS5A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDS5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDS5A were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: PDS5A were set to Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: PDS5A was set to GREEN
Added comment: Boone 2026 reports 8 individuals from 8 unrelated families with heterozygous predicted damaging PDS5A variants (5 missense and 3 frameshift) and variable neurodevelopmental features without a unified syndrome. Inheritance of variants was 4 de novo, 2 unknown, and 2 inherited from unaffected parent.

PMID 30158690 reports 2 individuals from 2 unrelated families with heterozygous loss‑of‑function PDS5A variants and a CdLS‑like cohesinopathy. One individual had a paternally inherited PDS5A variant (p.E759*) and de novo ASXL3 variant (which explained most of phenotype). The other individual had a de novo PDS5A variant (c.654+5G>C).

No functional studies were presented.
Sources: Literature
Mendeliome v1.4570 Chirag Patel Added reviews for gene FMO4 from panel Mendeliome
Mendeliome v1.4569 FMO4 Chirag Patel Marked gene: FMO4 as ready
Mendeliome v1.4569 FMO4 Chirag Patel Gene: fmo4 has been classified as Red List (Low Evidence).
Mendeliome v1.4569 FMO4 Chirag Patel gene: FMO4 was added
gene: FMO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FMO4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FMO4 were set to 41714691, 28940097
Phenotypes for gene: FMO4 were set to Neurodevelopmental disorder, MONDO:0700092; FMO4 related
Review for gene: FMO4 was set to RED
Added comment: 3 individuals from 2 unrelated families with mild‑moderate intellectual disability without additional systemic features. One family had a homozygous loss-of-function frameshift (p.(Ala520GlyfsTer13)) and the other had a homozygous missense variant (p.(Pro28His)) in FMO4 gene. Parents were heterozygous carriers. No functional validation was performed, but the gene is expressed in the brain and the variants are ultra‑rare in population databases.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.131 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.131 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.406 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.406 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.405 Chirag Patel Added reviews for gene SPIDR from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.130 Chirag Patel Added reviews for gene SPIDR from panel Mendeliome
Mendeliome v1.4568 SPIDR Chirag Patel Classified gene: SPIDR as Green List (high evidence)
Mendeliome v1.4568 SPIDR Chirag Patel Gene: spidr has been classified as Green List (High Evidence).
Mendeliome v1.4567 SPIDR Chirag Patel reviewed gene: SPIDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 41644825; Phenotypes: Primary ovarian failure, MONDO:0005387; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.106 BICC1 Chirag Patel edited their review of gene: BICC1: Added comment: PMID 41677782 provides 4 individuals from 3 families with very early‑onset polycystic kidney disease (VEO-PKD).
-2 siblings from consanguineous family with homozygous missense BICC1 variant (p.Ser240Pro)(absent gnomAD). One of the siblings also had a PKD2 variant (c.1445T>G, p.Phe482Cys).
-1 individual with BICC1 missense variant (c.2462G>A, p.Gly821Glu)(3025 HTZ gnomAD) inherited from his father (2 small renal cysts in 1 kidney), and a de novo PKD2 variant (c.1894T>C, p.Cys632Arg).
-1 individual with BICC1 splice variant (c.1179+1G>T)(absent gnomAD) inherited from his father, and a de novo PKD1 variant (c.11942C>T, p.Ala3981Val).

Functional assays of the p.Ser240Pro and p.Gly821Glu variants demonstrated hypomorphic loss‑of‑function (CRISPR knock‑in HEK293T, Xenopus rescue, protein stability). Hypothesis that BICC1 cooperates functionally with PKD1 and PKD2, and that BICC1 variants may aggravate PKD severity.; Changed publications: 41677782; Changed phenotypes: Polycystic kidney disease, MONDO:0020642; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.106 Chirag Patel Added reviews for gene BICC1 from panel Mendeliome
Mendeliome v1.4567 Chirag Patel Added reviews for gene BICC1 from panel Mendeliome
Mendeliome v1.4566 BICC1 Chirag Patel edited their review of gene: BICC1: Added comment: PMID 41677782 provides 4 individuals from 3 families with very early‑onset polycystic kidney disease (VEO-PKD).
-2 siblings from consanguineous family with homozygous missense BICC1 variant (p.Ser240Pro)(absent gnomAD). One of the siblings also had a PKD2 variant (c.1445T>G, p.Phe482Cys).
-1 individual with BICC1 missense variant (c.2462G>A, p.Gly821Glu)(3025 HTZ gnomAD) inherited from his father (2 small renal cysts in 1 kidney), and a de novo PKD2 variant (c.1894T>C, p.Cys632Arg).
-1 individual with BICC1 splice variant (c.1179+1G>T)(absent gnomAD) inherited from his father, and a de novo PKD1 variant (c.11942C>T, p.Ala3981Val).
Functional assays of the p.Ser240Pro and p.Gly821Glu variants demonstrated hypomorphic loss‑of‑function (CRISPR knock‑in HEK293T, Xenopus rescue, protein stability). Hypothesis that BICC1 cooperates functionally with PKD1 and PKD2, and that BICC1 variants may aggravate PKD severity.; Changed publications: 41677782; Changed phenotypes: Polycystic kidney disease, MONDO:0020642; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.30 AGRP Zornitza Stark Marked gene: AGRP as ready
Severe early-onset obesity v1.30 AGRP Zornitza Stark Gene: agrp has been classified as Red List (Low Evidence).
Severe early-onset obesity v1.30 Zornitza Stark Copied gene AGRP from panel Mendeliome
Severe early-onset obesity v1.30 AGRP Zornitza Stark gene: AGRP was added
gene: AGRP was added to Severe early-onset obesity. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: AGRP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGRP were set to 41680086
Phenotypes for gene: AGRP were set to {Leanness, inherited} 601665; {Obesity, late-onset} 601665; Obesity disorder, MONDO:0011122, AGRP-related
Mendeliome v1.4566 AGRP Zornitza Stark Phenotypes for gene: AGRP were changed from {Leanness, inherited} 601665; {Obesity, late-onset} 601665 to {Leanness, inherited} 601665; {Obesity, late-onset} 601665; Obesity disorder, MONDO:0011122, AGRP-related
Mendeliome v1.4565 AGRP Zornitza Stark Publications for gene: AGRP were set to
Mendeliome v1.4564 AGRP Zornitza Stark Mode of inheritance for gene: AGRP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4563 AGRP Zornitza Stark edited their review of gene: AGRP: Added comment: PMID 41680086 reports a single individual carrying a heterozygous missense AGRP variant p.Arg79Cys associated with severe early‑onset childhood obesity; segregation analysis confirms co‑segregation; no functional studies were performed.; Changed publications: 41680086; Changed phenotypes: Obesity disorder, MONDO:0011122, AGRP-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v1.129 C11orf80 Zornitza Stark Phenotypes for gene: C11orf80 were changed from Recurrent hydatidiform mole 4, MIM # 618432 to Infertility disorder, MONDO:0005047, C11orf80-related; hydatidiform mole, recurrent, 4, MONDO:0032747
Infertility and Recurrent Pregnancy Loss v1.128 C11orf80 Zornitza Stark Publications for gene: C11orf80 were set to 30388401; 36732965
Infertility and Recurrent Pregnancy Loss v1.127 C11orf80 Zornitza Stark reviewed gene: C11orf80: Rating: AMBER; Mode of pathogenicity: None; Publications: 41644825, 30388401; Phenotypes: Infertility disorder, MONDO:0005047, C11orf80-related, hydatidiform mole, recurrent, 4, MONDO:0032747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4563 C11orf80 Zornitza Stark Phenotypes for gene: C11orf80 were changed from Recurrent hydatidiform mole 4, MIM # 618432 to Infertility disorder, MONDO:0005047, C11orf80-related; hydatidiform mole, recurrent, 4, MONDO:0032747
Mendeliome v1.4562 C11orf80 Zornitza Stark Publications for gene: C11orf80 were set to 30388401; 36732965
Mendeliome v1.4561 C11orf80 Zornitza Stark edited their review of gene: C11orf80: Added comment: PMID 41644825 reports a Turkish consanguineous family with a homozygous splice‑site TOP6BL variant (c.523+1G>C) causing adult‑onset non‑obstructive azoospermia (NOA) and meiotic arrest; mouse Top6bl knockout recapitulates the male‑infertility phenotype. PMID 30388401 describes two unrelated families with biallelic TOP6BL loss‑of‑function alleles (c.783dup and c.1501T>C) presenting with recurrent complete hydatidiform mole (CHM) and miscarriage.

Maintain Amber rating as unclear whether these two disease associations are related or distinct.; Changed publications: 41644825, 30388401; Changed phenotypes: Infertility disorder, MONDO:0005047, C11orf80-related, hydatidiform mole, recurrent, 4, MONDO:0032747
Deafness_IsolatedAndComplex v1.335 TNC Zornitza Stark Publications for gene: TNC were set to 23936043
Deafness_IsolatedAndComplex v1.334 TNC Zornitza Stark Classified gene: TNC as Green List (high evidence)
Deafness_IsolatedAndComplex v1.334 TNC Zornitza Stark Gene: tnc has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.333 TNC Zornitza Stark edited their review of gene: TNC: Added comment: Five additional unrelated families (12 patients) with heterozygous loss‑of‑function TNC variants (frameshift c.5738_5745dup, nonsense c.1615C>T, nonsense c.1641C>A, missense c.2852C>T, splice‑site c.5247A>T) reported in association with deafness. Phenotypes range from childhood‑onset fluctuating loss to adult low‑frequency progressive loss. Two of the variants are present at relatively high pop frequencies in gnomAD.; Changed rating: GREEN; Changed publications: 23936043, 40203778, 39720982, 39020321, 38640279, 35062939
Mendeliome v1.4561 TNC Zornitza Stark Publications for gene: TNC were set to 23936043; 34093110; 33763067
Mendeliome v1.4560 TNC Zornitza Stark Classified gene: TNC as Green List (high evidence)
Mendeliome v1.4560 TNC Zornitza Stark Gene: tnc has been classified as Green List (High Evidence).
Mendeliome v1.4559 TNC Zornitza Stark edited their review of gene: TNC: Added comment: Five additional unrelated families (12 patients) with heterozygous loss‑of‑function TNC variants (frameshift c.5738_5745dup, nonsense c.1615C>T, nonsense c.1641C>A, missense c.2852C>T, splice‑site c.5247A>T) reported in association with deafness. Phenotypes range from childhood‑onset fluctuating loss to adult low‑frequency progressive loss.

Two of the variants are present at relatively high pop frequencies in gnomAD.; Changed rating: GREEN; Changed publications: 40203778, 39720982, 39020321, 38640279, 35062939; Changed phenotypes: autosomal dominant nonsyndromic hearing loss 56, MONDO:0014283
Congenital Heart Defect v0.531 MYH6 Sangavi Sivagnanasundram Phenotypes for gene: MYH6 were changed from to MYH-6 related congenital heart defects MONDO:0800442
Congenital Heart Defect v0.530 MYH6 Sangavi Sivagnanasundram Mode of inheritance for gene: MYH6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.529 MYH6 Sangavi Sivagnanasundram reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008375; Phenotypes: MYH-6 related congenital heart defects MONDO:0800442; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v1.18 NRDC Zornitza Stark Marked gene: NRDC as ready
Arthrogryposis v1.18 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.388 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Genetic Epilepsy v1.388 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.387 NRDC Zornitza Stark Source Literature was added to NRDC.
Rating Changed from No List (delete) to Red List (low evidence)
Genetic Epilepsy v1.386 NRDC Zornitza Stark All sources for gene: NRDC were removed
Arthrogryposis v1.18 Zornitza Stark Copied gene NRDC from panel Mendeliome
Arthrogryposis v1.18 NRDC Zornitza Stark gene: NRDC was added
gene: NRDC was added to Arthrogryposis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Phenotypes for gene: NRDC were set to Neurodevelopmental disorder, MONDO:0700092, NRDC-related
Genetic Epilepsy v1.385 NRDC Zornitza Stark Marked gene: NRDC as ready
Genetic Epilepsy v1.385 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Genetic Epilepsy v1.385 Zornitza Stark Copied gene NRDC from panel Intellectual disability syndromic and non-syndromic
Genetic Epilepsy v1.385 NRDC Zornitza Stark gene: NRDC was added
gene: NRDC was added to Genetic Epilepsy. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654; 41734767; 41449824
Phenotypes for gene: NRDC were set to Neurodevelopmental disorder, MONDO:0700092, NRDC-related
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Marked gene: NRDC as ready
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.703 NRDC Zornitza Stark Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Intellectual disability syndromic and non-syndromic v1.702 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.702 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.701 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.420 NRDC Zornitza Stark Marked gene: NRDC as ready
Microcephaly v1.420 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Microcephaly v1.420 NRDC Zornitza Stark Publications for gene: NRDC were set to 41449824; 28017472; 34582790; 19935654
Microcephaly v1.419 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Microcephaly v1.419 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Microcephaly v1.418 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4559 NRDC Zornitza Stark Marked gene: NRDC as ready
Mendeliome v1.4559 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Mendeliome v1.4559 NRDC Zornitza Stark Classified gene: NRDC as Green List (high evidence)
Mendeliome v1.4559 NRDC Zornitza Stark Gene: nrdc has been classified as Green List (High Evidence).
Mendeliome v1.4558 NRDC Zornitza Stark reviewed gene: NRDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41734767, 41449824, 28017472; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NRDC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4558 Bryony Thompson Copied gene RPS27A from panel Haematological malignancies
Mendeliome v1.4558 RPS27A Bryony Thompson gene: RPS27A was added
gene: RPS27A was added to Mendeliome. Sources: Expert Review Red,Curated sources
Mode of inheritance for gene: RPS27A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPS27A were set to 28297620; 24680683; 26942564
Phenotypes for gene: RPS27A were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR)
Mendeliome v1.4557 Bryony Thompson Copied gene RPL36 from panel Haematological malignancies
Mendeliome v1.4557 RPL36 Bryony Thompson gene: RPL36 was added
gene: RPL36 was added to Mendeliome. Sources: Expert Review Amber,Curated sources
Mode of inheritance for gene: RPL36 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL36 were set to 28297620; 19061985; 39923319
Phenotypes for gene: RPL36 were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR); Diamond-Blackfan anemia MONDO:0015253
Diamond Blackfan anaemia v1.16 Bryony Thompson Copied gene RPL36 from panel Haematological malignancies
Diamond Blackfan anaemia v1.16 RPL36 Bryony Thompson gene: RPL36 was added
gene: RPL36 was added to Diamond Blackfan anaemia. Sources: Expert Review Amber,Curated sources
Mode of inheritance for gene: RPL36 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL36 were set to 28297620; 19061985; 39923319
Phenotypes for gene: RPL36 were set to Osteosarcoma, soft tissue sarcomas; Diamond Blackfan Anemia; MDS, AML; Class: BM failure syndrome (typ AR); Diamond-Blackfan anemia MONDO:0015253
Bone Marrow Failure v1.141 MDM4 Zornitza Stark Phenotypes for gene: MDM4 were changed from bone marrow failure syndrome MONDO:0000159, MDM4-related to bone marrow failure syndrome 6, MONDO:0030015
Bone Marrow Failure v1.140 MDM4 Zornitza Stark Classified gene: MDM4 as Green List (high evidence)
Bone Marrow Failure v1.140 MDM4 Zornitza Stark Gene: mdm4 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.139 MDM4 Zornitza Stark reviewed gene: MDM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41758987; Phenotypes: bone marrow failure syndrome 6, MONDO:0030015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4556 MDM4 Zornitza Stark Phenotypes for gene: MDM4 were changed from bone marrow failure syndrome MONDO:0000159, MDM4-related to bone marrow failure syndrome 6, MONDO:0030015
Mendeliome v1.4555 MDM4 Zornitza Stark Publications for gene: MDM4 were set to 32300648; 33104793
Mendeliome v1.4554 MDM4 Zornitza Stark Classified gene: MDM4 as Green List (high evidence)
Mendeliome v1.4554 MDM4 Zornitza Stark Gene: mdm4 has been classified as Green List (High Evidence).
Mendeliome v1.4553 MDM4 Zornitza Stark reviewed gene: MDM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 41758987, 32300648; Phenotypes: bone marrow failure syndrome 6, MONDO:0030015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Ataxia v1.194 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Ataxia v1.194 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.701 Zornitza Stark Copied gene VWA3B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.701 VWA3B Zornitza Stark gene: VWA3B was added
gene: VWA3B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035; 41673450; 37772257
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Ataxia v1.194 VWA3B Zornitza Stark Phenotypes for gene: VWA3B were changed from ?Spinocerebellar ataxia, autosomal recessive 22 to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Ataxia v1.193 VWA3B Zornitza Stark Classified gene: VWA3B as Green List (high evidence)
Ataxia v1.193 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Ataxia v1.192 VWA3B Zornitza Stark reviewed gene: VWA3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 41673450, 37772257, 26157035; Phenotypes: Spinocerebellar ataxia, autosomal recessive 22, MIM# 616948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4553 VWA3B Zornitza Stark Publications for gene: VWA3B were set to 26157035
Mendeliome v1.4552 VWA3B Zornitza Stark Classified gene: VWA3B as Green List (high evidence)
Mendeliome v1.4552 VWA3B Zornitza Stark Gene: vwa3b has been classified as Green List (High Evidence).
Mendeliome v1.4551 VWA3B Zornitza Stark reviewed gene: VWA3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 41673450, 37772257, 26157035; Phenotypes: Spinocerebellar ataxia, autosomal recessive 22, MIM# 616948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Marked gene: MYOM1 as ready
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v1.61 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045 to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related
Dilated Cardiomyopathy v1.60 MYOM1 Zornitza Stark Deleted their comment
Dilated Cardiomyopathy v1.60 Zornitza Stark Copied gene MYOM1 from panel Mendeliome
Dilated Cardiomyopathy v1.60 MYOM1 Zornitza Stark gene: MYOM1 was added
gene: MYOM1 was added to Dilated Cardiomyopathy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
disputed tags were added to gene: MYOM1.
Mode of inheritance for gene: MYOM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYOM1 were set to 27600940; 26656175; 21256114
Phenotypes for gene: MYOM1 were set to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.4551 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Dilated cardiomyopathy, MONDO:0005021, MYOM1-related; Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.4550 MYOM1 Zornitza Stark Classified gene: MYOM1 as Amber List (moderate evidence)
Mendeliome v1.4550 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4549 MYOM1 Zornitza Stark changed review comment from: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation; to: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation

Note DISPUTED association with HCM.
Mendeliome v1.4549 MYOM1 Zornitza Stark edited their review of gene: MYOM1: Added comment: PMID 41702018 reports 28 unrelated families with heterozygous loss‑of‑function MYOM1 variants associated dilated cardiomyopathy. Individuals identified from UK Biobank, hence limited clinical and segregation data. Mouse Myom1 knock‑down functional validation; Changed rating: AMBER; Changed publications: 41702018, 26036949; Changed phenotypes: Dilated cardiomyopathy, MONDO:0005021, MYOM1-related
Severe early-onset obesity v1.29 BDNF Zornitza Stark Marked gene: BDNF as ready
Severe early-onset obesity v1.29 BDNF Zornitza Stark Gene: bdnf has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v1.29 BDNF Zornitza Stark Deleted their comment
Mendeliome v1.4549 BDNF Zornitza Stark changed review comment from: Refuted gene, disease association has been removed in OMIM.; to: Refuted gene, disease association with central hypoventilation has been removed in OMIM.
Severe early-onset obesity v1.29 Zornitza Stark Copied gene BDNF from panel Mendeliome
Severe early-onset obesity v1.29 BDNF Zornitza Stark gene: BDNF was added
gene: BDNF was added to Severe early-onset obesity. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: BDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BDNF were set to 41680086; 37329217; 33442278; 32493978; 30926952; 28397838
Phenotypes for gene: BDNF were set to Obesity disorder, MONDO:0011122, BDNF-related
Mendeliome v1.4549 BDNF Zornitza Stark Phenotypes for gene: BDNF were changed from to Obesity disorder, MONDO:0011122, BDNF-related
Mendeliome v1.4548 BDNF Zornitza Stark Publications for gene: BDNF were set to
Mendeliome v1.4547 BDNF Zornitza Stark Mode of inheritance for gene: BDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4546 BDNF Zornitza Stark Classified gene: BDNF as Amber List (moderate evidence)
Mendeliome v1.4546 BDNF Zornitza Stark Gene: bdnf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4545 BDNF Zornitza Stark edited their review of gene: BDNF: Added comment: 9 families with heterozygous variants causing severe early‑onset obesity, often with hyperphagia and neuro‑behavioral features) reported across multiple papers. Variants are generally missense with little supporting data. The PMID 32493978 report provides the first experimental functional validation (cell‑based assays showing impaired pro‑BDNF processing and loss‑of‑function).; Changed rating: AMBER; Changed publications: 41680086, 37329217, 33442278, 32493978, 30926952, 28397838; Changed phenotypes: Obesity disorder, MONDO:0011122, BDNF-related
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark Marked gene: ZNF124 as ready
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark Gene: znf124 has been classified as Red List (Low Evidence).
Retinitis pigmentosa v0.243 Zornitza Stark Copied gene ZNF124 from panel Mendeliome
Retinitis pigmentosa v0.243 ZNF124 Zornitza Stark gene: ZNF124 was added
gene: ZNF124 was added to Retinitis pigmentosa. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ZNF124 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF124 were set to 41708596
Phenotypes for gene: ZNF124 were set to Retinitis pigmentosa, MONDO:0019200, ZNF124-related
Mendeliome v1.4545 ZNF124 Zornitza Stark Marked gene: ZNF124 as ready
Mendeliome v1.4545 ZNF124 Zornitza Stark Gene: znf124 has been classified as Red List (Low Evidence).
Mendeliome v1.4545 ZNF124 Zornitza Stark gene: ZNF124 was added
gene: ZNF124 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF124 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF124 were set to 41708596
Phenotypes for gene: ZNF124 were set to Retinitis pigmentosa, MONDO:0019200, ZNF124-related
Review for gene: ZNF124 was set to RED
Added comment: PMID 41708596 report 2 individuals from a consanguineous family with retinitis pigmentosa and a homozygous splice‑site loss‑of‑function variant c.219‑1delG in ZNF124. The variant co‑segregates with disease and mouse retina‑specific knockout recapitulates the retinal degeneration phenotype through loss of ZNF124‑mediated activation of MSX2.
Sources: Literature
Fetal anomalies v1.543 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Fetal anomalies v1.543 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Heterotaxy v1.45 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Heterotaxy v1.45 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Heterotaxy v1.45 Zornitza Stark Copied gene CCDC57 from panel Mendeliome
Heterotaxy v1.45 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Heterotaxy. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Fetal anomalies v1.543 Zornitza Stark Copied gene CCDC57 from panel Mendeliome
Fetal anomalies v1.543 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Fetal anomalies. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Mendeliome v1.4544 CCDC57 Zornitza Stark Marked gene: CCDC57 as ready
Mendeliome v1.4544 CCDC57 Zornitza Stark Gene: ccdc57 has been classified as Red List (Low Evidence).
Mendeliome v1.4544 CCDC57 Zornitza Stark gene: CCDC57 was added
gene: CCDC57 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC57 were set to 41758249
Phenotypes for gene: CCDC57 were set to Visceral heterotaxy, MONDO:0018677, CCDC57-related
Review for gene: CCDC57 was set to RED
Added comment: PMID 41758249 reports a single individual with compound heterozygous missense variants presenting with isolated laterality disorder (situs inversus, dextrocardia, chronic sinusitis). Xenopus rescue experiments showed that wild‑type CCDC57 mRNA rescues ciliary structure and fluid flow, whereas patient variant mRNAs fail to rescue, supporting loss‑of‑function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark Marked gene: XPOT as ready
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark Marked gene: XPOT as ready
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark Marked gene: XPOT as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4543 ICOSLG Sangavi Sivagnanasundram reviewed gene: ICOSLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 34694545; Phenotypes: immunodeficiency 119, MONDO:0970993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4543 GSX2 Sangavi Sivagnanasundram reviewed gene: GSX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39119454; Phenotypes: diencephalic-mesencephalic junction dysplasia syndrome 2, MONDO:0020762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 Zornitza Stark Copied gene XPOT from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.10 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Intellectual disability syndromic and non-syndromic v1.700 Zornitza Stark Copied gene XPOT from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.700 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Deafness_IsolatedAndComplex v1.333 Zornitza Stark Copied gene XPOT from panel Mendeliome
Deafness_IsolatedAndComplex v1.333 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Mendeliome v1.4543 XPOT Zornitza Stark Marked gene: XPOT as ready
Mendeliome v1.4543 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4543 XPOT Zornitza Stark Classified gene: XPOT as Green List (high evidence)
Mendeliome v1.4543 XPOT Zornitza Stark Gene: xpot has been classified as Green List (High Evidence).
Mendeliome v1.4542 XPOT Zornitza Stark gene: XPOT was added
gene: XPOT was added to Mendeliome. Sources: Literature
preprint tags were added to gene: XPOT.
Mode of inheritance for gene: XPOT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPOT were set to 10.64898/2026.01.28.26344748
Phenotypes for gene: XPOT were set to Syndromic disease, MONDO:0002254
Review for gene: XPOT was set to GREEN
Added comment: Preprint by Von Hardenberg et al 2026 reports 8 individuals from 5 unrelated families with biallelic loss‑of‑function XPOT variants presenting with childhood‑onset severe sensorineural hearing loss, recurrent infections/bronchiectasis, developmental delay and growth retardation. Functional studies show absent XPOT protein in patient fibroblasts, reduced TNF‑α translation, and xpot‑deficient zebrafish recapitulating the multisystem phenotype.

All reported variants are homozygous.
Sources: Literature
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Cataract v0.631 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Cataract v0.631 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.38 TTN Zornitza Stark edited their review of gene: TTN: Added comment: No evidence for association with rhabdomyolysis.; Changed rating: RED; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.59 CAP2 Elena Savva reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22945801; Phenotypes: Cardiomyopathy, dilated, 2I MIM#620462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.126 OTUD3 Peter McNaughton gene: OTUD3 was added
gene: OTUD3 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: OTUD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTUD3 were set to PMID: 41067575
Phenotypes for gene: OTUD3 were set to Ulcerative colitis
Review for gene: OTUD3 was set to AMBER
Added comment: Multigenerational family with a medically refractory colitis phenotype permitted identification of the A143T missense mutation in OTUD3 as the causal variant. Murine model replicating phenotype and demonstrating impaired intestinal barrier function.
Amber for single kindred.
Sources: Literature
Autoinflammatory Disorders v2.46 Chirag Patel Copied gene CTLA4 from panel Disorders of immune dysregulation
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel gene: CTLA4 was added
gene: CTLA4 was added to Autoinflammatory Disorders. Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 25213377; 25329329; 30377434
Phenotypes for gene: CTLA4 were set to Autoimmune lymphoproliferative syndrome, type V, MIM# 616100
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel Marked gene: CTLA4 as ready
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel Gene: ctla4 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v2.46 Chirag Patel Copied gene CTLA4 from panel Autoimmune Lymphoproliferative Syndrome
Autoinflammatory Disorders v2.46 CTLA4 Chirag Patel gene: CTLA4 was added
gene: CTLA4 was added to Autoinflammatory Disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CTLA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTLA4 were set to 39060684; 38302222
Phenotypes for gene: CTLA4 were set to Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation MIM#616100; autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency MONDO:0014493
Mendeliome v1.4541 PLEKHA7 Lucy Spencer Phenotypes for gene: PLEKHA7 were changed from Cleft lip and palate to Cleft lip/palate MONDO:0016044, PLEKHA7-related
Atrial Fibrillation v1.7 MYL4 Zornitza Stark Marked gene: MYL4 as ready
Atrial Fibrillation v1.7 MYL4 Zornitza Stark Gene: myl4 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.7 NUP155 Zornitza Stark Marked gene: NUP155 as ready
Atrial Fibrillation v1.7 NUP155 Zornitza Stark Gene: nup155 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.699 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.699 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Cataract v0.631 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Cataract v0.631 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Cataract. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Cardiomyopathy_Paediatric v0.224 Zornitza Stark Copied gene WDR59 from panel Mendeliome
Cardiomyopathy_Paediatric v0.224 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Amber,Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Mendeliome v1.4540 WDR59 Zornitza Stark Marked gene: WDR59 as ready
Mendeliome v1.4540 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4540 WDR59 Zornitza Stark Classified gene: WDR59 as Amber List (moderate evidence)
Mendeliome v1.4540 WDR59 Zornitza Stark Gene: wdr59 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4539 WDR59 Zornitza Stark gene: WDR59 was added
gene: WDR59 was added to Mendeliome. Sources: Literature
founder tags were added to gene: WDR59.
Mode of inheritance for gene: WDR59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR59 were set to 41715954
Phenotypes for gene: WDR59 were set to Syndromic disease, MONDO:0002254
Review for gene: WDR59 was set to AMBER
Added comment: PMID 41715954 reports six individuals from four unrelated families with biallelic WDR59 variants causing early‑onset autosomal recessive syndromic dilated cardiomyopathy, cataract, facial dysmorphism, growth retardation and developmental delay. Three Saudi families share the homozygous missense founder variant c.2887G>A (p.Gly963Arg) and a French family carries compound heterozygous intronic splice‑site variants; RNA‑seq shows aberrant splicing and reduced WDR59 expression, supporting loss‑of‑function. Segregation data confirm recessive inheritance, making WDR59 a diagnostic‑grade gene.

Founder variant accounts for three of four families, hence Amber rating
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark Marked gene: WAPL as ready
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.698 Zornitza Stark Copied gene WAPL from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.698 WAPL Zornitza Stark gene: WAPL was added
gene: WAPL was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: WAPL.
Mode of inheritance for gene: WAPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: WAPL were set to complex neurodevelopmental disorder, MONDO:0100038
Mendeliome v1.4538 WAPL Zornitza Stark Marked gene: WAPL as ready
Mendeliome v1.4538 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Mendeliome v1.4538 WAPL Zornitza Stark Classified gene: WAPL as Green List (high evidence)
Mendeliome v1.4538 WAPL Zornitza Stark Gene: wapl has been classified as Green List (High Evidence).
Mendeliome v1.4537 WAPL Zornitza Stark gene: WAPL was added
gene: WAPL was added to Mendeliome. Sources: Literature
preprint tags were added to gene: WAPL.
Mode of inheritance for gene: WAPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Phenotypes for gene: WAPL were set to complex neurodevelopmental disorder, MONDO:0100038
Review for gene: WAPL was set to GREEN
Added comment: PMID 30158690 reports a single de novo missense WAPL variant in a patient with mild CdLS‑like cohesinopathy, while a preprint (Boone et al 2026) describes 27 unrelated individuals with heterozygous loss‑of‑function or damaging missense WAPL variants presenting with a neurodevelopmental syndrome (developmental delay/intellectual disability, facial dysmorphism, congenital anomalies such as clubfoot). Combined, the two studies provide 28 unrelated families supporting WAPL haploinsufficiency as a cause of a complex neurodevelopmental disorder, with mouse and iPSC functional data corroborating pathogenicity.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark Marked gene: TFDP3 as ready
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.127 Zornitza Stark Copied gene TFDP3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.127 TFDP3 Zornitza Stark gene: TFDP3 was added
gene: TFDP3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TFDP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TFDP3 were set to 41634254
Phenotypes for gene: TFDP3 were set to Infertility disorder, MONDO:0005047, TFDP3-related
Mendeliome v1.4536 TFDP3 Zornitza Stark Marked gene: TFDP3 as ready
Mendeliome v1.4536 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Mendeliome v1.4536 TFDP3 Zornitza Stark Classified gene: TFDP3 as Green List (high evidence)
Mendeliome v1.4536 TFDP3 Zornitza Stark Gene: tfdp3 has been classified as Green List (High Evidence).
Mendeliome v1.4535 TFDP3 Zornitza Stark gene: TFDP3 was added
gene: TFDP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TFDP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TFDP3 were set to 41634254
Phenotypes for gene: TFDP3 were set to Infertility disorder, MONDO:0005047, TFDP3-related
Review for gene: TFDP3 was set to GREEN
Added comment: PMID 41634254 reports 8 individuals from 7 families with X‑linked hemizygous TFDP3 loss‑of‑function variants presenting with severe oligoasthenoteratozoospermia. Affected males have dramatically reduced sperm concentration, motility, and abnormal morphology. Functional studies show reduced TFDP3 protein in patient sperm and recapitulation of the infertility phenotype in TFDP3 knock‑down cynomolgus monkeys with increased E2F1‑mediated apoptosis.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.139 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Bone Marrow Failure v1.139 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 Zornitza Stark Copied gene RPA2 from panel Mendeliome
Pulmonary Fibrosis_Interstitial Lung Disease v1.9 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Bone Marrow Failure v1.139 Zornitza Stark Copied gene RPA2 from panel Mendeliome
Bone Marrow Failure v1.139 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Bone Marrow Failure. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Mendeliome v1.4534 RPA2 Zornitza Stark Marked gene: RPA2 as ready
Mendeliome v1.4534 RPA2 Zornitza Stark Gene: rpa2 has been classified as Red List (Low Evidence).
Mendeliome v1.4534 RPA2 Zornitza Stark gene: RPA2 was added
gene: RPA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RPA2 were set to 41703052; 39231615
Phenotypes for gene: RPA2 were set to Telomere syndrome, MONDO:0100137, RPA2-related
Review for gene: RPA2 was set to RED
Added comment: PMID 41703052 reports a 6‑year‑old individual from a consanguineous family who is homozygous for the splice‑site variant c.409‑2A>G (p.Q136_K138del). The patient presented with early‑onset bone‑marrow failure, immunodeficiency, microcephaly, dysmorphic features and severely short telomeres. The heterozygous parents are asymptomatic carriers. Functional studies showed ~50% reduction of RPA2 protein, destabilization of the OB‑fold ssDNA‑binding groove, impaired telomere binding, severe telomere shortening, increased telomere variant repeats and chromosome end‑to‑end fusions, supporting a loss‑of‑function mechanism.

PMID 39231615 reports 2 individuals from 2 unrelated families with a heterozygous missense variant c.767A>G (p.Y256C) presenting with adult‑onset telomere biology disorder characterized by pleuroparenchymal fibroelastosis/interstitial lung disease, short telomeres, bone‑marrow failure (macrocytic anemia, myelodysplastic syndrome), liver disease and osteoporosis. Variant is ultra‑rare (gnomAD v4 1 het) and predicted deleterious. Functional studies (RPE1 knock‑in cell lines, RFWD3 interaction and ubiquitination assays, ATR signaling, telomere length assays, and a mouse model lethal in homozygous state) demonstrate loss‑of‑function effects, supporting pathogenicity. Both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening.
Sources: Literature
Ataxia v1.192 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Ataxia v1.192 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v1.16 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Mitochondrial disease v1.16 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark Marked gene: RAD51AP2 as ready
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.126 Zornitza Stark Copied gene RAD51AP2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.126 RAD51AP2 Zornitza Stark gene: RAD51AP2 was added
gene: RAD51AP2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RAD51AP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51AP2 were set to 41644825; 36153927
Phenotypes for gene: RAD51AP2 were set to Infertility disorder, MONDO:0005047, RAD51AP2-related
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Marked gene: RAD51AP2 as ready
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Classified gene: RAD51AP2 as Amber List (moderate evidence)
Mendeliome v1.4533 RAD51AP2 Zornitza Stark Gene: rad51ap2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v1.16 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Mitochondrial disease v1.16 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Mitochondrial disease. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Mendeliome v1.4532 RAD51AP2 Zornitza Stark gene: RAD51AP2 was added
gene: RAD51AP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAD51AP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD51AP2 were set to 41644825; 36153927
Phenotypes for gene: RAD51AP2 were set to Infertility disorder, MONDO:0005047, RAD51AP2-related
Review for gene: RAD51AP2 was set to AMBER
Added comment: PMID 41644825 reports one male patient from a Turkish consanguineous family and PMID 36153927 reports two brothers from an unrelated family; together three individuals from two unrelated families carry biallelic loss‑of‑function RAD51AP2 variants and present with non‑obstructive azoospermia and meiotic arrest. Both studies demonstrate autosomal recessive inheritance, and a mouse Rad51ap2 knockout recapitulates the infertility phenotype, providing functional support for causality.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.697 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.697 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Genetic Epilepsy v1.384 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Genetic Epilepsy v1.384 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Infertility and Recurrent Pregnancy Loss v1.125 Zornitza Stark removed gene:C17orf80 from the panel
Ataxia v1.192 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Ataxia v1.192 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Ataxia. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark Marked gene: PIWIL1 as ready
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.124 Zornitza Stark Copied gene PIWIL1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.124 PIWIL1 Zornitza Stark gene: PIWIL1 was added
gene: PIWIL1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PIWIL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIWIL1 were set to 41706354; 39122675; 37335463; 36379263; 33877510; 28552346
Phenotypes for gene: PIWIL1 were set to Infertility disorder, MONDO:0005047, PIWIL1-related
Mendeliome v1.4531 PIWIL1 Zornitza Stark Marked gene: PIWIL1 as ready
Mendeliome v1.4531 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4531 PIWIL1 Zornitza Stark Classified gene: PIWIL1 as Amber List (moderate evidence)
Mendeliome v1.4531 PIWIL1 Zornitza Stark Gene: piwil1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4530 PIWIL1 Zornitza Stark gene: PIWIL1 was added
gene: PIWIL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIWIL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIWIL1 were set to 41706354; 39122675; 37335463; 36379263; 33877510; 28552346
Phenotypes for gene: PIWIL1 were set to Infertility disorder, MONDO:0005047, PIWIL1-related
Review for gene: PIWIL1 was set to AMBER
Added comment: PMID 28552346 reports three unrelated families with heterozygous PIWIL1 missense variants causing idiopathic azoospermia; mouse knock‑in and rescue experiments provide functional support. PMID 41706354 and PMID 39122675 describe two unrelated families with recessive loss‑of‑function PIWIL1 frameshift/stop‑gain variants leading to non‑obstructive azoospermia and spermatogenic arrest, confirmed by immunohistochemistry and piRNA profiling. PMID 37335463 identifies a compound‑heterozygous patient and four heterozygous carriers of rare missense/truncating PIWIL1 variants, and a Miwi R371W knock‑in mouse recapitulates subfertility.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.123 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Infertility and Recurrent Pregnancy Loss v1.123 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.123 Zornitza Stark Copied gene C17orf80 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.123 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Mendeliome v1.4529 C17orf80 Zornitza Stark Marked gene: C17orf80 as ready
Mendeliome v1.4529 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4529 C17orf80 Zornitza Stark Classified gene: C17orf80 as Amber List (moderate evidence)
Mendeliome v1.4529 C17orf80 Zornitza Stark Gene: c17orf80 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4528 C17orf80 Zornitza Stark gene: C17orf80 was added
gene: C17orf80 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: C17orf80.
Mode of inheritance for gene: C17orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf80 were set to 41720819
Phenotypes for gene: C17orf80 were set to Mitochondrial disease, MONDO:0044970
Review for gene: C17orf80 was set to AMBER
Added comment: PMID 41720819 reports 3 individuals from 2 unrelated families with biallelic MTNAP1 variants (hmz missense and hmz LoF) presenting with early‑onset global developmental delay, ataxia, spasticity, seizures and progressive cerebral and cerebellar atrophy. Functional studies in proband-derived fibroblasts and MTNAP1-silenced neuronal cells implicated profound mitochondrial fragmentation, reduced oxidative phosphorylation capacity, increased reactive oxygen species accumulation, and premature senescence-like stress responses. Structural modeling and biophysical analyses revealed that the p.G553R variant destabilizes the MTNAP1 fold, disrupts its DNA- and membrane-binding interfaces, and induces aberrant aggregation, leading to loss of mitochondrial integrity.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.122 CCDC113 Zornitza Stark Marked gene: CCDC113 as ready
Infertility and Recurrent Pregnancy Loss v1.122 CCDC113 Zornitza Stark Gene: ccdc113 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.122 Zornitza Stark Copied gene CCDC113 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.122 CCDC113 Zornitza Stark gene: CCDC113 was added
gene: CCDC113 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CCDC113 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC113 were set to 41645397; 41645397
Phenotypes for gene: CCDC113 were set to Infertility disorder, MONDO:0005047, CCDC113-related
Mendeliome v1.4527 CCDC113 Zornitza Stark Marked gene: CCDC113 as ready
Mendeliome v1.4527 CCDC113 Zornitza Stark Gene: ccdc113 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4527 CCDC113 Zornitza Stark Classified gene: CCDC113 as Amber List (moderate evidence)
Mendeliome v1.4527 CCDC113 Zornitza Stark Gene: ccdc113 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4526 CCDC113 Zornitza Stark gene: CCDC113 was added
gene: CCDC113 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC113 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC113 were set to 41645397; 41645397
Phenotypes for gene: CCDC113 were set to Infertility disorder, MONDO:0005047, CCDC113-related
Review for gene: CCDC113 was set to AMBER
Added comment: PMID 41645397 reports three affected men from two unrelated families who carry biallelic missense variants in CFAP263 (CCDC113) and present with severe oligoasthenoteratozoospermia. The variants cosegregate as recessive, are absent from population databases, and functional studies (reduced protein stability and a Ccdc113 knockout mouse model) recapitulate the infertility phenotype.
Sources: Literature
Mendeliome v1.4525 ASCL5 Zornitza Stark Marked gene: ASCL5 as ready
Mendeliome v1.4525 ASCL5 Zornitza Stark Gene: ascl5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4525 ASCL5 Zornitza Stark Classified gene: ASCL5 as Amber List (moderate evidence)
Mendeliome v1.4525 ASCL5 Zornitza Stark Gene: ascl5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4524 ASCL5 Zornitza Stark gene: ASCL5 was added
gene: ASCL5 was added to Mendeliome. Sources: Literature
founder tags were added to gene: ASCL5.
Mode of inheritance for gene: ASCL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASCL5 were set to 41673016
Phenotypes for gene: ASCL5 were set to Tooth disorder, MONDO:0006999, ASCL5-related
Review for gene: ASCL5 was set to AMBER
Added comment: [PMID 41673016] reports 17 individuals from 6 unrelated families with heterozygous missense ASCL5 c.274G>A (p.Glu92Lys) variants presenting with autosomal‑dominant lobodontia, characterized by supernumerary cusps, single pyramidal roots, and taurodontism. The variant fully co‑segregates with disease, is absent from population databases, and functional studies (CRISPR knock‑in mouse, luciferase reporter, RNA‑seq) demonstrate loss‑of‑function of ASCL5 transcriptional activation.

Amber rating due to this being a likely founder variant and not necessarily perceived as disease.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.121 ASB9 Zornitza Stark Marked gene: ASB9 as ready
Infertility and Recurrent Pregnancy Loss v1.121 ASB9 Zornitza Stark Gene: asb9 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.121 Zornitza Stark Copied gene ASB9 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.121 ASB9 Zornitza Stark gene: ASB9 was added
gene: ASB9 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ASB9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ASB9 were set to 41730923
Phenotypes for gene: ASB9 were set to Infertility disorder, MONDO:0005047, ASB9-related
Mendeliome v1.4523 ASB9 Zornitza Stark edited their review of gene: ASB9: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4523 ASB9 Zornitza Stark Marked gene: ASB9 as ready
Mendeliome v1.4523 ASB9 Zornitza Stark Gene: asb9 has been classified as Green List (High Evidence).
Mendeliome v1.4523 ASB9 Zornitza Stark Mode of inheritance for gene: ASB9 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4522 ASB9 Zornitza Stark Classified gene: ASB9 as Green List (high evidence)
Mendeliome v1.4522 ASB9 Zornitza Stark Gene: asb9 has been classified as Green List (High Evidence).
Mendeliome v1.4521 ASB9 Zornitza Stark gene: ASB9 was added
gene: ASB9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASB9 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: ASB9 were set to 41730923
Phenotypes for gene: ASB9 were set to Infertility disorder, MONDO:0005047, ASB9-related
Review for gene: ASB9 was set to GREEN
Added comment: PMID 41730923 reports four unrelated male patients with hemizygous missense ASB9 variants presenting with idiopathic oligoasthenoteratozoospermia. Functional studies reveal reduced ASB9 protein stability, impaired interaction with TUBB4A, and mouse knockout/knock‑in models recapitulate the infertility phenotype, supporting a loss‑of‑function disease mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.696 RDH11 Lucy Spencer changed review comment from: PMID: 41459630 proband with oligodontia and malocclusion, dysmorphic hands and feet, microcephaly, ASD but otherwise normal development, homozygous for Cys72*. following the genetic findings the proband had an ophthalmological examination which showed a mild retinopathy consisting of yellow deposits and hyperpigmentation within the RPE, but the patient was visually asymptomatic at age 7. However in the original family PMID: 24916380 progressive visual acuity decrease did not occur until ages 10 or 8 in the 3 affected siblings. This family also had widely spaced oligodontia and malocclusion.; to: PMID: 41459630 proband with oligodontia and malocclusion, dysmorphic hands and feet, microcephaly, ASD but otherwise normal development, homozygous for Cys72*. following the genetic findings the proband had an ophthalmological examination which showed a mild retinopathy consisting of yellow deposits and hyperpigmentation within the RPE, but the patient was visually asymptomatic at age 7. However in the original family PMID: 24916380 progressive visual acuity decrease did not occur until ages 10 or 8 in the 3 affected siblings. This family also had widely spaced oligodontia and malocclusion.

ID also reported in PMID: 24916380 and PMID 34988992 families
Syndromic Retinopathy v0.248 RDH11 Lucy Spencer Classified gene: RDH11 as Green List (high evidence)
Syndromic Retinopathy v0.248 RDH11 Lucy Spencer Gene: rdh11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.696 RDH11 Lucy Spencer Classified gene: RDH11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.696 RDH11 Lucy Spencer Gene: rdh11 has been classified as Green List (High Evidence).
Mendeliome v1.4520 RDH11 Lucy Spencer Publications for gene: RDH11 were set to 24916380; 15634683; 30731079; 18326732
Syndromic Retinopathy v0.247 Lucy Spencer Added reviews for gene RDH11 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.695 Lucy Spencer Copied gene RDH11 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.695 RDH11 Lucy Spencer gene: RDH11 was added
gene: RDH11 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: RDH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH11 were set to 24916380; 15634683; 30731079; 18326732
Phenotypes for gene: RDH11 were set to Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108
Mendeliome v1.4519 RDH11 Lucy Spencer Classified gene: RDH11 as Green List (high evidence)
Mendeliome v1.4519 RDH11 Lucy Spencer Gene: rdh11 has been classified as Green List (High Evidence).
Mendeliome v1.4518 RDH11 Lucy Spencer reviewed gene: RDH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 41459630; Phenotypes: Retinal dystrophy, juvenile cataracts, and short stature syndrome, MIM# 616108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.148 RAB1A Lucy Spencer Classified gene: RAB1A as Green List (high evidence)
Hereditary Spastic Paraplegia v1.148 RAB1A Lucy Spencer Gene: rab1a has been classified as Green List (High Evidence).
Mendeliome v1.4518 RAB1A Lucy Spencer Publications for gene: RAB1A were set to 37924809
Mendeliome v1.4517 RAB1A Lucy Spencer Classified gene: RAB1A as Green List (high evidence)
Mendeliome v1.4517 RAB1A Lucy Spencer Gene: rab1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.694 RAB1A Lucy Spencer Publications for gene: RAB1A were set to PMID: 37924809
Intellectual disability syndromic and non-syndromic v1.693 RAB1A Lucy Spencer Classified gene: RAB1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.693 RAB1A Lucy Spencer Gene: rab1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.692 Lucy Spencer Added reviews for gene RAB1A from panel Mendeliome
Hereditary Spastic Paraplegia v1.147 Lucy Spencer Copied gene RAB1A from panel Mendeliome
Hereditary Spastic Paraplegia v1.147 RAB1A Lucy Spencer gene: RAB1A was added
gene: RAB1A was added to Hereditary Spastic Paraplegia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB1A were set to 37924809
Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, RAB1A-related
Mendeliome v1.4516 RAB1A Lucy Spencer changed review comment from: PMID: 37924809 2 families with PTCs inherited from affected fathers (Arg175* and Thr43fs), another proband with a PTC and unknown inheritance (Val22fs) and a 4th proband with a de novo missense (Leu28Pro). All variants were absent from gnomad except Val22fs which has a PTC within the first 102 nucleotides so is likely to escape NMD. Arg175* was in the last exon and also escapes NMD and removes two C-terminal prenylated cysteine residues that direct the subcellular localization and activity of Rab proteins. Studies in transfected cells showed a construct truncated protein failed to localise to the golgi. In KO cells both Arg175* and Leu28pro failed to rescue the phenotype.

PMID: 38091987: two new probands with NDD and spasticity. One de novo for Ser200*, 2nd patient de novo for Arg175* same variant previously identified in a family from the previous paper. This new paper also says they have an aditional 3rd family with 2 affected siblings and an affected mother who also have Arg175*.; to: PMID: 37924809 2 families with PTCs inherited from affected fathers (Arg175* and Thr43fs), another proband with a PTC and unknown inheritance (Val22fs) and a 4th proband with a de novo missense (Leu28Pro). All variants were absent from gnomad except Val22fs which has a PTC within the first 102 nucleotides so is likely to escape NMD. Arg175* was in the last exon and also escapes NMD and removes two C-terminal prenylated cysteine residues that direct the subcellular localization and activity of Rab proteins. Studies in transfected cells showed a construct truncated protein failed to localise to the golgi. In KO cells both Arg175* and Leu28pro failed to rescue the phenotype.

The individual with the missense variant had a more severe phenotype involving abnormal MRI findings and spondyloepimetaphyseal dysplasia, the functional studies suggested this variant has a dominant negative effect which would explain this.

PMID: 38091987: two new probands with NDD and spasticity. One de novo for Ser200*, 2nd patient de novo for Arg175* same variant previously identified in a family from the previous paper. This new paper also says they have an aditional 3rd family with 2 affected siblings and an affected mother who also have Arg175*.
Mendeliome v1.4516 RAB1A Lucy Spencer reviewed gene: RAB1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37924809, 38091987; Phenotypes: neurodevelopmental disorder MONDO:0700092, RAB1A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4516 TKFC Sarah Milton reviewed gene: TKFC: Rating: AMBER; Mode of pathogenicity: None; Publications: 38697782, 32004446; Phenotypes: Triokinase and FMN cyclase deficiency syndrome, MONDO:0032927; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.35 KCNJ11 Zornitza Stark changed review comment from: There are arguments both for and against including this gene in gNBS -- decision may depend on level of integration between clinical-laboratory pathways and turnaround time.; to: Reviewed at Gene List subcommittee meeting 13/3/26.

There are arguments both for and against including this gene in gNBS -- decision may depend on level of integration between clinical-laboratory pathways and turnaround time.
Genomic newborn screening: ICoNS v0.35 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Genomic newborn screening: ICoNS v0.35 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: ICoNS v0.35 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from Familial Hyperinsulinemic hypoglycemia 2 (CHI); MODY type 13; neonatale diabetes; DEND Syndrome to Diabetes mellitus, transient neonatal, 3 610582 Diabetes, permanent neonatal, with or without neurologic features 606176 Hyperinsulinemic hypoglycemia, familial, 2 601820
Genomic newborn screening: ICoNS v0.34 KCNJ11 Zornitza Stark Classified gene: KCNJ11 as Amber List (moderate evidence)
Genomic newborn screening: ICoNS v0.34 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: ICoNS v0.33 KCNJ11 Zornitza Stark reviewed gene: KCNJ11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, transient neonatal, 3 610582 Diabetes, permanent neonatal, with or without neurologic features 606176 Hyperinsulinemic hypoglycemia, familial, 2 601820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.33 BCKDHA Zornitza Stark Marked gene: BCKDHA as ready
Genomic newborn screening: ICoNS v0.33 BCKDHA Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.33 BCKDHA Zornitza Stark Phenotypes for gene: BCKDHA were changed from to Maple syrup urine disease, type Ia, MIM# 248600
Genomic newborn screening: ICoNS v0.32 BCKDHA Zornitza Stark Classified gene: BCKDHA as Green List (high evidence)
Genomic newborn screening: ICoNS v0.32 BCKDHA Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.31 BCKDHA Zornitza Stark reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type Ia, MIM# 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.31 BCKDHB Zornitza Stark Marked gene: BCKDHB as ready
Genomic newborn screening: ICoNS v0.31 BCKDHB Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.31 BCKDHB Zornitza Stark Phenotypes for gene: BCKDHB were changed from to Maple syrup urine disease, type Ib, MIM# 248600
Genomic newborn screening: ICoNS v0.30 BCKDHB Zornitza Stark Classified gene: BCKDHB as Green List (high evidence)
Genomic newborn screening: ICoNS v0.30 BCKDHB Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence).
Genomic newborn screening: ICoNS v0.29 BCKDHB Zornitza Stark reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type Ib, MIM# 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: ICoNS v0.29 KCNJ11 Val Jacquemin gene: KCNJ11 was added
gene: KCNJ11 was added to Genomic newborn screening: ICoNS. Sources: Other
Mode of inheritance for gene: KCNJ11 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KCNJ11 were set to PMID: 28824061; PMID: 32027066; PMID: 21674179; PMID: 38226203; PMID: 26908106
Phenotypes for gene: KCNJ11 were set to Familial Hyperinsulinemic hypoglycemia 2 (CHI); MODY type 13; neonatale diabetes; DEND Syndrome
Review for gene: KCNJ11 was set to RED
Added comment: 1) Mutations in the KCNJ11 gene affect the ATP-sensitive potassium (KATP) channel in pancreatic β-cells, which links cellular metabolism to insulin secretion. When gain-of-function mutations occur, the KATP channel remains excessively open, preventing β-cell depolarization and impairing insulin release; this mechanism causes monogenic diabetes that can present either as Neonatal diabetes or as MODY13 depending largely on mutation severity and age of onset. Heterozygous activating mutations in KCNJ11 were first shown to cause neonatal diabetes, demonstrating that increased KATP channel activity suppresses insulin secretion and leads to hyperglycemia (Shimomura & Maejima 2017). The most severe activating mutations can also affect neuronal KATP channels, leading to the syndromic form known as DEND syndrome, characterized by developmental delay, epilepsy, and neonatal diabetes. Because milder activating variants may allow partial insulin secretion, diabetes can appear later in life and be classified as MODY13, placing both conditions on a clinical spectrum of KATP channel overactivity (De Franco et al. 2020). As activating mutations in KCNJ11 can lead either to neonatal diabetes or to MODY13, genotype alone does not reliably predict the age of disease onset. MODY13 typically manifests much later in life; reported cases show onset ranging from approximately 9 to 28 years of age, with many patients developing diabetes during adolescence (Chen et al. 2023). Because gNBS programs generally target disorders that produce symptoms in early childhood (e.g., before about 5 years of age) and require early intervention, MODY13 falls outside the scope of these screening criteria. Consequently, detecting a KCNJ11 activating mutation in a newborn would not allow clinicians to determine whether the child will develop neonatal diabetes in infancy or a later-onset MODY13 phenotype. For this reason, neonatal diabetes cannot reliably be included as a standalone condition in gNBS based solely on KCNJ11 variants.

In contrast, the opposite mechanism, loss-of-function mutations in KATP channel genes such as KCNJ11, causes Congenital hyperinsulinism (familial hyperinsulinemic hypoglycemia), where defective channels cannot open, leading to persistent β-cell depolarization and inappropriate insulin secretion even during hypoglycemia. Most severe KATP-related CHI cases follow an autosomal recessive inheritance pattern, although some mutations can act dominantly and produce milder phenotypes (Kapoor et al. 2011). When focusing specifically on autosomal recessive KCNJ11-related CHI, biallelic inactivating mutations disrupt KATP channel activity and typically result in severe neonatal hypoglycemia. From a screening perspective, CHI typically presents with symptomatic hypoglycemia very shortly after birth, meaning it is usually detected rapidly through clinical glucose monitoring, thereby limiting the added value of gNBS (Stanley, 2016).

In their comparative analysis of genomic newborn sequencing initiatives, Thomas Minten and colleagues reported that the KCNJ11 gene is included in 17 of the 27 gNBS programs evaluated in the study. These programs include BabySeq, BabyDetect, BeginNGS, Early Check, the GUARDIAN study, NESTS (Newborn Sequencing in Genomic Medicine and Public Health), gnSTAR, the Chen et al. newborn sequencing cohort, the Wang et al. newborn sequencing study, the Yang et al. multicenter sequencing study, the PerkinElmer genomic newborn screening panel, the PerkinElmer GS program, the NeoExome panel, BabyScreen+, NeoSeq, the targeted panel described by Huang et al. (inborn disorders of neonates), and the sequencing pilot described by Jian et al. (WGS screening pilot). However, the analysis compares gene inclusion rather than specific target conditions, and it is therefore not always clear which disease associated with KCNJ11 (e.g., monogenic diabetes or congenital hyperinsulinism) is intended to be screened for in each program.

2) ClinGen curation
The KCNJ11 gene has been curated by Clinical Genome Resource (ClinGen) for its role in monogenic diabetes. ClinGen has classified the association between KCNJ11 and KATP-channel–related diabetes as Definitive, based on strong genetic and experimental evidence. Pathogenic variants in KCNJ11 are well established causes of Neonatal diabetes and MODY13 through gain-of-function effects on the KATP channel. The gene is also associated with Congenital hyperinsulinism through loss-of-function variants. ClinGen curation therefore supports a strong gene–disease relationship for both monogenic diabetes and hyperinsulinism.

3) Treatability and evidence
Clinical studies have demonstrated that a large proportion of individuals with KCNJ11-related neonatal diabetes can successfully switch from insulin injections to sulfonylureas, leading to improved glycemic control and quality of life (Pearson et al., 2006, New England Journal of Medicine). In addition to improving metabolic control, early treatment may also improve neurological outcomes in some patients with syndromic forms of the disease such as DEND syndrome.
For CHI (caused by loss-of-function KATP mutations), treatment may include diazoxide therapy, which acts as a KATP channel opener, although many recessive KATP-channel cases are diazoxide-unresponsive and may require pancreatectomy. Early diagnosis is therefore clinically important to prevent severe hypoglycemia and neurological damage.

4) Impact of treatment
The clinical impact of appropriate treatment can be substantial:
KCNJ11 neonatal diabetes --> switch from insulin to oral sulfonylureas, improved glycemic control, reduced treatment burden, potential improvement in neurological symptoms when therapy is initiated early
Congenital hyperinsulinism --> diazoxide or octreotide therapy may prevent hypoglycemia,
early recognition prevents hypoglycemic brain injury

5) Issues with genomic screening
Despite the strong gene–disease association and available treatments, several challenges exist for genomic newborn screening of KCNJ11.
Phenotypic ambiguity --> same mutation type in KCNJ11 can cause neonatal diabetes or MODY13 which have different ages of onset

Technical sequencing considerations --> from a sequencing perspective, KCNJ11 is technically straightforward to analyze: small gene, no pseudogenes, good coverage in both exome and genome sequencing

Clinical detection without genomics --> for autosomal recessive KCNJ11-related congenital hyperinsulinism, symptoms usually appear shortly after birth with severe hypoglycemia. Because neonatal glucose levels are routinely monitored, many cases are detected rapidly through standard clinical care, limiting the additional value of genomic newborn screening. Neonatal diabetes presents with persistent hyperglycemia in infancy, often leading to rapid clinical investigation.
Sources: Other
Genomic newborn screening: ICoNS v0.29 BCKDHB José Manuel González de Aledo Castillo gene: BCKDHB was added
gene: BCKDHB was added to Genomic newborn screening: ICoNS. Sources: Expert Review,Literature
Mode of inheritance for gene: BCKDHB was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Gene disease association evidence:

Disease: Maple syrup urine disease type 1A (MSUD1B), autosomal recessive.
Gene: BCKDHB encodes the E1β subunit of the branched-chain α-ketoacid dehydrogenase complex. Loss of function at the protein level reduces BCKD activity and causes toxic accumulation of branched-chain amino acids and ketoacids. BCKDHB variants account for ~35% of MSUD cases

Curation by ClinGen:
ClinGen gene–disease validity: Definitive

Treatability and evidence behind that including impact of treatment:
Standard care is dietary leucine restriction, BCAA-free supplements, supplementation with isoleucine and valine as needed, and frequent biochemical monitoring. Acute metabolic crises need urgent metabolic management.
Early treatment of asymptomatic infants detected by NBS means that most who would have developed neonatal manifestations remain asymptomatic with good treatment adherence . NBS cases has better survival than clinically diagnosed cases: 62.5% versus 5.2%
For severe MSUD, liver transplantation can be an option

Issues with genomic screening
Main problem would be turnaround time

Any variants of interest
The pathogenic spectrum is dominated by missense variants, also there also reported truncating variants.
c.548G>C (p.Arg183Pro): well-known Ashkenazi Jewish founder variant.

Who has excluded in genomic newborn screening it and why:
BeginNGS in previous genelists, now included

Traditional newborn screening in any jurisdiction:
Included in RUSP and most NBS wordlwide
Sources: Expert Review, Literature
Genomic newborn screening: ICoNS v0.29 BCKDHA José Manuel González de Aledo Castillo gene: BCKDHA was added
gene: BCKDHA was added to Genomic newborn screening: ICoNS. Sources: Literature
Mode of inheritance for gene: BCKDHA was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Gene–disease association evidence:
Disease: Maple syrup urine disease type 1A (MSUD1A), autosomal recessive.
Gene: BCKDHA encodes the E1α subunit of the branched-chain α-ketoacid dehydrogenase complex. Loss of function at the protein level reduces BCKD activity and causes toxic accumulation of branched-chain amino acids and ketoacids. BCKDHA variants account for ~45% of MSUD cases

Curation by ClinGen:
ClinGen gene–disease validity: Definitive

Treatability and evidence behind that including impact of treatment:
Standard care is dietary leucine restriction, BCAA-free supplements, supplementation with isoleucine and valine as needed, and frequent biochemical monitoring. Acute metabolic crises need urgent metabolic management.
Early treatment of asymptomatic infants detected by NBS means that most who would have developed neonatal manifestations remain asymptomatic with good treatment adherence . NBS cases has better survival than clinically diagnosed cases: 62.5% versus 5.2%
For severe MSUD, liver transplantation can be an option

Issues with genomic screening
Main problem would be turnaround time

Any variants of interest
The pathogenic spectrum is dominated by missense variants, also there also reported truncating variants.
c.1312T>A, p.Tyr438Asn (Old Order/Swiss Mennonites). High prevalence in these populations

Who has excluded in genomic newborn screening it and why:
BeginNGS in previous genelists, now included

Traditional newborn screening in any jurisdiction:
Included in RUSP and most NBS wordlwide
Sources: Literature
Mendeliome v1.4516 ANLN Zornitza Stark Publications for gene: ANLN were set to 24676636; 30002222; 34819827; 38322629; 37957688
Mendeliome v1.4515 ANLN Zornitza Stark edited their review of gene: ANLN: Added comment: PMID 41492027: two individuals from a single family with missense variant and FSGS phenotype. Insufficient segregation. Retain Amber rating as many of the previously reported variants have high pop frequencies.; Changed publications: 24676636, 30002222, 34819827, 38322629, 37957688, 41492027
Proteinuria v0.239 ANLN Zornitza Stark Publications for gene: ANLN were set to 24676636; 30002222; 34819827; 38322629; 37957688
Proteinuria v0.238 ANLN Zornitza Stark edited their review of gene: ANLN: Added comment: PMID 41492027: two individuals from a single family with missense variant and FSGS phenotype. Insufficient segregation. Retain Amber rating as many of the previously reported variants have high pop frequencies.; Changed publications: 24676636, 30002222, 41492027
Mendeliome v1.4515 AHR Zornitza Stark Publications for gene: AHR were set to 29726989; 31896775
Mendeliome v1.4514 AHR Zornitza Stark edited their review of gene: AHR: Added comment: PMID 38922562 reports third family with foveal hypoplasia, homozygous variant. Retain Amber rating.; Changed publications: 31009037, 33193710, 38922562
Mendeliome v1.4514 JKAMP Zornitza Stark Marked gene: JKAMP as ready
Mendeliome v1.4514 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Genetic Epilepsy v1.383 JKAMP Zornitza Stark Marked gene: JKAMP as ready
Genetic Epilepsy v1.383 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Mendeliome v1.4514 Zornitza Stark Copied gene JKAMP from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.4514 JKAMP Zornitza Stark gene: JKAMP was added
gene: JKAMP was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: JKAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JKAMP were set to 41643666
Phenotypes for gene: JKAMP were set to Neurodevelopmental disorder with seizures and impaired intellectual and language development, MIM# 621533
Microcephaly v1.418 JKAMP Zornitza Stark Marked gene: JKAMP as ready
Microcephaly v1.418 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Microcephaly v1.418 Zornitza Stark Copied gene JKAMP from panel Intellectual disability syndromic and non-syndromic
Microcephaly v1.418 JKAMP Zornitza Stark gene: JKAMP was added
gene: JKAMP was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: JKAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JKAMP were set to 41643666
Phenotypes for gene: JKAMP were set to Neurodevelopmental disorder with seizures and impaired intellectual and language development, MIM# 621533
Genetic Epilepsy v1.383 Zornitza Stark Copied gene JKAMP from panel Intellectual disability syndromic and non-syndromic
Genetic Epilepsy v1.383 JKAMP Zornitza Stark gene: JKAMP was added
gene: JKAMP was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: JKAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JKAMP were set to 41643666
Phenotypes for gene: JKAMP were set to Neurodevelopmental disorder with seizures and impaired intellectual and language development, MIM# 621533
Intellectual disability syndromic and non-syndromic v1.691 JKAMP Zornitza Stark Marked gene: JKAMP as ready
Intellectual disability syndromic and non-syndromic v1.691 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.691 JKAMP Zornitza Stark Classified gene: JKAMP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.691 JKAMP Zornitza Stark Gene: jkamp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.690 JKAMP Zornitza Stark gene: JKAMP was added
gene: JKAMP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: JKAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JKAMP were set to 41643666
Phenotypes for gene: JKAMP were set to Neurodevelopmental disorder with seizures and impaired intellectual and language development, MIM# 621533
Review for gene: JKAMP was set to GREEN
Added comment: 14 individuals from 10 families reported. All had moderate to profound neurodevelopmental delay, intellectual disability, and infantile-onset epilepsy. Six were nonverbal, and the remaining individuals spoke only a few words. Five individuals had neurodevelopmental regression. Three individuals died suddenly; death was associated with seizures or status epilepticus in two. Thirteen individuals had hypotonia, 5 had visual impairment, 5 had microcephaly, and 1 had hearing loss. Brain MRIs showed cortical or cerebral atrophy in 11, delayed myelination in 6, and diffuse demyelinating disease in 1.
Sources: Literature
Mendeliome v1.4513 MDH1 Rylee Peters Publications for gene: MDH1 were set to 31538237
Mendeliome v1.4512 MDH1 Rylee Peters reviewed gene: MDH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 40959467, 31538237; Phenotypes: Developmental and epileptic encephalopathy 88, MIM#618959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.607 Sarah Milton Copied Region LMNB1 upstream region from panel Mendeliome
Regression v0.607 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Regression. Sources: Literature
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
Mendeliome v1.4512 LMNB1 upstream region Sarah Milton Region: LMNB1 upstream region was added
Region: LMNB1 upstream region was added to Mendeliome. Sources: Literature
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
Review for Region: LMNB1 upstream region was set to GREEN
Added comment: LMNB1 encodes an intermediate filament proteins which play a role in forming the nuclear lamina lining the inner nuclear membrane. Overexpression of LMNB1 via gene duplication has been well established to cause adult-onset autosomal dominant demyelinating leukodystrophy, MONDO:0008215.

PMID: 30842973; 30697589; 25701871 report deletional forms of the phenotype. With an approx 167kb minimal critical region upstream of LMNB1 that has been associated with adult-onset autosomal dominant demyelinating leukodystrophy in 5 families with over 35 individuals affected.

The deletion is upstream of the promoter of LMNB1 and involves other protein coding genes (ALDH7A1/PHAX) that are thought to be bystanders. The proposed molecular mechanism of disease for these deletions is disruption of a topologically associated domain boundary resulting in overexpression of LMNB1. This occurs by placing the promoter in closer proximity to an upstream enhancer element.

Extensive functional studies support this hypothesis and affected individuals have been shown to have upregulated LMNB1 protein on Western blot.

Note the coordinates differ between families with much larger deletions reported in many affected individuals.
Sources: Literature
Mendeliome v1.4511 FRMD4A Sangavi Sivagnanasundram reviewed gene: FRMD4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34869127; Phenotypes: severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, MONDO:0014787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.301 Sangavi Sivagnanasundram Added reviews for gene FAM92A from panel Mendeliome
Mendeliome v1.4511 FAM92A Sangavi Sivagnanasundram reviewed gene: FAM92A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38853702; Phenotypes: Polydactyly, postaxial, type A9, MONDO:0032603; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4511 TNNI1 Sarah Milton reviewed gene: TNNI1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30886088; Phenotypes: Sudden unexpected infant death, MONDO:1010116, TNNI1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4511 ADIPOR1 Zornitza Stark Phenotypes for gene: ADIPOR1 were changed from Retinitis pigmentosa to Retinitis pigmentosa, MONDO:0019200, ADIPOR1-related; Hypertrophic cardiomyopathy, MONDO:0005045, ADIPOR1-related
Mendeliome v1.4510 ADIPOR1 Zornitza Stark Publications for gene: ADIPOR1 were set to 27655171; 26662040
Mendeliome v1.4509 ADIPOR1 Zornitza Stark edited their review of gene: ADIPOR1: Added comment: PMID 33523960 reports five individuals from four unrelated South‑Asian families carrying heterozygous missense variants (c.470T>A p.L157H, c.436G>A p.V146M, c.433T>A p.F145I) who present with HCM; three of the five also have diabetes mellitus. All variants are absent or ultra‑rare in public databases, three are de novo events, and functional assays in rat cardiomyocytes and a Cre‑V146M transgenic mouse model show hyperactivation of p38/mTOR and/or ERK pathways, cardiomyocyte hypertrophy, metabolic dysregulation and rescue by rapamycin.; Changed publications: 27655171, 26662040, 33523960; Changed phenotypes: Retinitis pigmentosa, MONDO:0019200, ADIPOR1-related, Hypertrophic cardiomyopathy, MONDO:0005045, ADIPOR1-related
Hypertrophic cardiomyopathy v1.25 ADIPOR1 Zornitza Stark Marked gene: ADIPOR1 as ready
Hypertrophic cardiomyopathy v1.25 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v1.25 ADIPOR1 Zornitza Stark Classified gene: ADIPOR1 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v1.25 ADIPOR1 Zornitza Stark Gene: adipor1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v1.24 ADIPOR1 Zornitza Stark gene: ADIPOR1 was added
gene: ADIPOR1 was added to Hypertrophic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: ADIPOR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADIPOR1 were set to 33523960
Phenotypes for gene: ADIPOR1 were set to Hypertrophic cardiomyopathy, MONDO:0005045, ADIPOR1-related
Review for gene: ADIPOR1 was set to AMBER
Added comment: The study reports five individuals from four unrelated South‑Asian families carrying heterozygous missense variants (c.470T>A p.L157H, c.436G>A p.V146M, c.433T>A p.F145I) who present with HCM; three of the five also have diabetes mellitus. All variants are absent or ultra‑rare in public databases, three are de novo events, and functional assays in rat cardiomyocytes and a Cre‑V146M transgenic mouse model show hyperactivation of p38/mTOR and/or ERK pathways, cardiomyocyte hypertrophy, metabolic dysregulation and rescue by rapamycin.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v1.52 CYS1 Lucy Spencer Phenotypes for gene: CYS1 were changed from Polycystic kidney disease, MONDO:0020642 to Polycystic kidney disease MONDO:0020642, CYS1-related
Renal Ciliopathies and Nephronophthisis v1.51 CYS1 Lucy Spencer Publications for gene: CYS1 were set to 34521872
Renal Ciliopathies and Nephronophthisis v1.50 CYS1 Lucy Spencer Classified gene: CYS1 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.50 CYS1 Lucy Spencer Gene: cys1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.49 Lucy Spencer Added reviews for gene CYS1 from panel Mendeliome
Renal Macrocystic Disease v0.105 Lucy Spencer Copied gene CYS1 from panel Mendeliome
Renal Macrocystic Disease v0.105 CYS1 Lucy Spencer gene: CYS1 was added
gene: CYS1 was added to Renal Macrocystic Disease. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 41720266; 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease MONDO:0020642, CYS1-related
Mendeliome v1.4509 CYS1 Lucy Spencer Classified gene: CYS1 as Green List (high evidence)
Mendeliome v1.4509 CYS1 Lucy Spencer Gene: cys1 has been classified as Green List (High Evidence).
Mendeliome v1.4508 CYS1 Lucy Spencer Phenotypes for gene: CYS1 were changed from Polycystic kidney disease, MONDO:0020642 to Polycystic kidney disease MONDO:0020642, CYS1-related
Mendeliome v1.4507 CYS1 Lucy Spencer Publications for gene: CYS1 were set to 34521872
Mendeliome v1.4506 CYS1 Lucy Spencer reviewed gene: CYS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41720266, 34521872; Phenotypes: Polycystic kidney disease MONDO:0020642, CYS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4506 FAM20B Sangavi Sivagnanasundram changed review comment from: 5 affected individuals from 2 unrelated families with autosomal recessive biallelic loss‑of‑function FAM20B variants presenting with lethal Desbuquois‑like skeletal dysplasia (short limbs, joint dislocations, craniofacial anomalies, intra‑uterine or neonatal death).

Gene upgraded to green in combination with previous reports of affected individuals and functional reports.; to: 5 affected individuals from 2 unrelated families with autosomal recessive biallelic loss‑of‑function FAM20B variants presenting with lethal Desbuquois‑like skeletal dysplasia (short limbs, joint dislocations, craniofacial anomalies, intra‑uterine or neonatal death).

Gene to remain as AMBER due to the potential overlap in families between the publications.
Proteinuria v0.238 Lucy Spencer Added reviews for gene RCAN1 from panel Mendeliome
Proteinuria v0.237 RCAN1 Lucy Spencer Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to Focal segmental glomerulosclerosis MONDO:0100313, RCAN1-related
Mendeliome v1.4506 RCAN1 Lucy Spencer Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to Focal segmental glomerulosclerosis MONDO:0100313, RCAN1-related
Mendeliome v1.4505 RCAN1 Lucy Spencer edited their review of gene: RCAN1: Added comment: PMID: 33863784 both missense reported in this paper are present in gnomad, 1 with over 100 hets the other with over 1000. this gene is borderline red; Changed rating: AMBER; Changed publications: 33863784; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4505 DISC1 Zornitza Stark Phenotypes for gene: DISC1 were changed from {Schizophrenia 9, susceptibility to} MIM#604906 to {Schizophrenia 9, susceptibility to} MIM#604906; Corpus callosum agenesis, MONDO:0009022, DISC1-related
Mendeliome v1.4504 DISC1 Zornitza Stark Publications for gene: DISC1 were set to 18945897
Mendeliome v1.4503 DISC1 Zornitza Stark Mode of inheritance for gene: DISC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4502 DISC1 Zornitza Stark reviewed gene: DISC1: Rating: RED; Mode of pathogenicity: None; Publications: 21739582; Phenotypes: Corpus callosum agenesis, MONDO:0009022, DISC1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.592 DISC1 Zornitza Stark Marked gene: DISC1 as ready
Callosome v0.592 DISC1 Zornitza Stark Gene: disc1 has been classified as Red List (Low Evidence).
Callosome v0.592 DISC1 Zornitza Stark Phenotypes for gene: DISC1 were changed from to Corpus callosum agenesis, MONDO:0009022, DISC1-related
Callosome v0.591 DISC1 Zornitza Stark Publications for gene: DISC1 were set to
Callosome v0.590 DISC1 Zornitza Stark Mode of inheritance for gene: DISC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.590 DISC1 Zornitza Stark Mode of inheritance for gene: DISC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.589 DISC1 Zornitza Stark Classified gene: DISC1 as Red List (low evidence)
Callosome v0.589 DISC1 Zornitza Stark Gene: disc1 has been classified as Red List (Low Evidence).
Callosome v0.588 DISC1 Zornitza Stark reviewed gene: DISC1: Rating: RED; Mode of pathogenicity: None; Publications: 21739582; Phenotypes: Corpus callosum agenesis, MONDO:0009022, DISC1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v1.121 DST Zornitza Stark Phenotypes for gene: DST were changed from congenital myopathy MONDO:0019952, DST-related to Congenital myopathy 29 with contractures, MIM# 621510; Lethal congenital contracture syndrome 12, MIM# 621511
Muscular dystrophy and myopathy_Paediatric v1.120 DST Zornitza Stark reviewed gene: DST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 29 with contractures, MIM# 621510, Lethal congenital contracture syndrome 12, MIM# 621511; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4502 DST Zornitza Stark Phenotypes for gene: DST were changed from Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653; Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425; congenital myopathy MONDO:0019952, DST-related to Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653; Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425; Congenital myopathy 29 with contractures, MIM# 621510; Lethal congenital contracture syndrome 12, MIM# 621511
Mendeliome v1.4501 DST Zornitza Stark edited their review of gene: DST: Added comment: The milder disorder is caused by variants that disrupt the DST-b isoform, while variants that affect both the DST-b and neuronal DST-a isoforms cause lethal congenital contracture syndrome.; Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653, Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425, Congenital myopathy 29 with contractures, MIM# 621510, Lethal congenital contracture syndrome 12, MIM# 621511
Arthrogryposis v1.17 DST Zornitza Stark Phenotypes for gene: DST were changed from congenital myopathy MONDO:0019952, DST-related to Congenital myopathy 29 with contractures, MIM# 621510; Lethal congenital contracture syndrome 12, MIM# 621511
Arthrogryposis v1.16 DST Zornitza Stark reviewed gene: DST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 29 with contractures, MIM# 621510, Lethal congenital contracture syndrome 12, MIM# 621511; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hyperinsulinism v1.51 AKT2 Krithika Murali Phenotypes for gene: AKT2 were changed from Hypoinsulinemic hypoglycemia with hemihypertrophy MIM#240900 to Hypoinsulinemic hypoglycemia and body hemihypertrophy - MONDO:0009416
Hyperinsulinism v1.51 AKT2 Krithika Murali Publications for gene: AKT2 were set to 21979934; 35602880; 24285683
Hyperinsulinism v1.50 AKT2 Krithika Murali Classified gene: AKT2 as Green List (high evidence)
Hyperinsulinism v1.50 AKT2 Krithika Murali Gene: akt2 has been classified as Green List (High Evidence).
Hyperinsulinism v1.49 AKT2 Krithika Murali reviewed gene: AKT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 24285683, 26003998, 35602880, 38344362; Phenotypes: Hypoinsulinemic hypoglycemia and body hemihypertrophy - MONDO:0009416; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal Dysplasia v0.109 TUFT1 Krithika Murali Publications for gene: TUFT1 were set to 36689522
Palmoplantar Keratoderma and Erythrokeratoderma v0.144 TUFT1 Krithika Murali Publications for gene: TUFT1 were set to 36689522
Ectodermal Dysplasia v0.108 TUFT1 Krithika Murali Classified gene: TUFT1 as Green List (high evidence)
Ectodermal Dysplasia v0.108 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.144 TUFT1 Krithika Murali Marked gene: TUFT1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.144 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.144 TUFT1 Krithika Murali Classified gene: TUFT1 as Green List (high evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.144 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.27 TUFT1 Krithika Murali Publications for gene: TUFT1 were set to 36689522; 36928819
Palmoplantar Keratoderma and Erythrokeratoderma v0.143 Krithika Murali Added reviews for gene TUFT1 from panel Mendeliome
Epidermolysis bullosa v1.26 TUFT1 Krithika Murali Marked gene: TUFT1 as ready
Epidermolysis bullosa v1.26 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.26 TUFT1 Krithika Murali Classified gene: TUFT1 as Green List (high evidence)
Epidermolysis bullosa v1.26 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.142 Krithika Murali Copied gene TUFT1 from panel Mendeliome
Palmoplantar Keratoderma and Erythrokeratoderma v0.142 TUFT1 Krithika Murali gene: TUFT1 was added
gene: TUFT1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFT1 were set to 36689522
Phenotypes for gene: TUFT1 were set to Woolly hair-skin fragility syndrome, MIM# 620415
Mendeliome v1.4501 TUFT1 Krithika Murali Publications for gene: TUFT1 were set to 36689522
Epidermolysis bullosa v1.25 Krithika Murali Added reviews for gene TUFT1 from panel Mendeliome
Mendeliome v1.4500 TUFT1 Krithika Murali Classified gene: TUFT1 as Green List (high evidence)
Mendeliome v1.4500 TUFT1 Krithika Murali Gene: tuft1 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.107 Krithika Murali Added reviews for gene TUFT1 from panel Mendeliome
Mendeliome v1.4499 TUFT1 Krithika Murali reviewed gene: TUFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37716648, 36689526, 36689522; Phenotypes: Woolly hair-skin fragility syndrome - MIM#620415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.689 RBFOX3 Lucy Spencer Classified gene: RBFOX3 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.689 RBFOX3 Lucy Spencer Gene: rbfox3 has been classified as Red List (Low Evidence).
Speech apraxia v1.28 Lucy Spencer Added reviews for gene RBFOX3 from panel Mendeliome
Genetic Epilepsy v1.382 Lucy Spencer Added reviews for gene RBFOX3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.688 Lucy Spencer Copied gene RBFOX3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.688 RBFOX3 Lucy Spencer gene: RBFOX3 was added
gene: RBFOX3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908; 40011789
Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related
Mendeliome v1.4499 RBFOX3 Lucy Spencer Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908
Mendeliome v1.4498 RBFOX3 Lucy Spencer reviewed gene: RBFOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: 40011789, 36117209; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v1.186 PRPH Lucy Spencer Mode of inheritance for gene: PRPH was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v1.185 PRPH Lucy Spencer Phenotypes for gene: PRPH were changed from {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400; Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related to Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related
Motor Neurone Disease v1.44 Lucy Spencer Added reviews for gene PRPH from panel Mendeliome
Hereditary Neuropathy v1.184 Lucy Spencer Copied gene PRPH from panel Mendeliome
Hereditary Neuropathy v1.184 PRPH Lucy Spencer gene: PRPH was added
gene: PRPH was added to Hereditary Neuropathy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRPH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PRPH were set to 20363051; 15322088; 15446584; 30992453; 32638105
Phenotypes for gene: PRPH were set to {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400; Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related
Mendeliome v1.4498 PRPH Lucy Spencer Publications for gene: PRPH were set to 20363051; 15322088; 15446584
Mendeliome v1.4497 PRPH Lucy Spencer Phenotypes for gene: PRPH were changed from {Amyotrophic lateral sclerosis, susceptibility to}, 105400 to {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400; Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related
Retinitis pigmentosa v0.242 PRPF6 Lucy Spencer Publications for gene: PRPF6 were set to 21549338; 32335390
Retinitis pigmentosa v0.241 PRPF6 Lucy Spencer Classified gene: PRPF6 as Green List (high evidence)
Retinitis pigmentosa v0.241 PRPF6 Lucy Spencer Gene: prpf6 has been classified as Green List (High Evidence).
Mendeliome v1.4496 PRPH Lucy Spencer reviewed gene: PRPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 30992453, 32638105; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to} MIM#105400, Hereditary motor and sensory neuropathy MONDO:0015358, PRPH-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v1.183 TDP1 Zornitza Stark Publications for gene: TDP1 were set to 31182267; 12244316
Hereditary Neuropathy v1.182 TDP1 Zornitza Stark commented on gene: TDP1: Additional family reported in PMID 39576382 with different homozygous missense, c.1432C>T (p.His478Tyr). The affected individual had severe hypotonia, ataxia, distal axonal neuropathy, seizures at 9‑10 months, kyphoscoliosis, hearing/vision loss and moderate cognitive impairment. No other supportive data.
Hereditary Neuropathy v1.182 TDP1 Zornitza Stark edited their review of gene: TDP1: Changed publications: 31182267, 12244316, 39576382
Ataxia v1.191 TDP1 Zornitza Stark Marked gene: TDP1 as ready
Ataxia v1.191 TDP1 Zornitza Stark Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Ataxia v1.191 TDP1 Zornitza Stark Publications for gene: TDP1 were set to 31182267; 12244316
Ataxia v1.190 TDP1 Zornitza Stark edited their review of gene: TDP1: Added comment: Additional family reported in PMID 39576382 with different homozygous missense, c.1432C>T (p.His478Tyr). The affected individual had severe hypotonia, ataxia, distal axonal neuropathy, seizures at 9‑10 months, kyphoscoliosis, hearing/vision loss and moderate cognitive impairment. No other supportive data.; Changed publications: 31182267, 12244316, 39576382
Mendeliome v1.4496 TDP1 Zornitza Stark Publications for gene: TDP1 were set to 31182267; 12244316
Retinitis pigmentosa v0.240 Lucy Spencer Added reviews for gene PRPF6 from panel Mendeliome
Mendeliome v1.4495 PRPF6 Lucy Spencer Publications for gene: PRPF6 were set to 21549338; 32335390
Mendeliome v1.4494 PRPF6 Lucy Spencer Classified gene: PRPF6 as Green List (high evidence)
Mendeliome v1.4494 PRPF6 Lucy Spencer Gene: prpf6 has been classified as Green List (High Evidence).
Mendeliome v1.4493 PRPF6 Lucy Spencer reviewed gene: PRPF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549338, 32335390, 36012314, 41584402; Phenotypes: Retinitis pigmentosa 60 MIM#613983; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4493 TDP1 Zornitza Stark changed review comment from: Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait.

Three families reported, however all from Middle East and had same homozygous missense variant.; to: Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait.

Three families reported, however all from Middle East and had same homozygous missense variant p.H493R.
Mendeliome v1.4493 TDP1 Zornitza Stark edited their review of gene: TDP1: Added comment: Additional family reported in PMID 39576382 with different homozygous missense, c.1432C>T (p.His478Tyr). The affected individual had severe hypotonia, ataxia, distal axonal neuropathy, seizures at 9‑10 months, kyphoscoliosis, hearing/vision loss and moderate cognitive impairment. No other supportive data.; Changed publications: 31182267, 12244316, 39576382
Cardiomyopathy_Paediatric v0.223 STX4 Zornitza Stark Marked gene: STX4 as ready
Cardiomyopathy_Paediatric v0.223 STX4 Zornitza Stark Gene: stx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4493 STX4 Zornitza Stark Publications for gene: STX4 were set to 36355422
Mendeliome v1.4492 STX4 Zornitza Stark edited their review of gene: STX4: Added comment: PMID 35599850: two unrelated families were identified with biallelic STX4 variants: Family 1 with a homozygous missense c.718C>T (p.Arg240Trp) and Family 2 compound heterozygous c.89_90delGC (p.Gly30Aspfs*28) and c.232+4A>C (splice‑site). Affected individuals present with early‑onset dilated cardiomyopathy, ventricular arrhythmia, sensorineural hearing loss, global developmental delay, hypotonia and multiple congenital anomalies; the second individual died perinatally. CRISPR‑generated stx4‑null zebrafish recapitulate cardiac dysfunction, bradycardia, reduced vesicle docking and altered Ca²⁺ handling. Transgenic rescue with wild‑type stx4 restores phenotype, whereas the R241W (human R240W) allele is hypomorphic and only partially rescues, supporting a loss‑of‑function mechanism. Pharmacologic L‑type Ca²⁺ channel modulation ameliorated bradycardia, further underscoring functional loss of STX4.

Unclear if this is a separate disease association or whether it will be part of a spectrum with the previous isolated deafness reports.; Changed rating: AMBER; Changed publications: 36355422, 35599850; Changed phenotypes: Deafness, autosomal recessive 123, MIM# 620745; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.223 Zornitza Stark Copied gene STX4 from panel Deafness_IsolatedAndComplex
Cardiomyopathy_Paediatric v0.223 STX4 Zornitza Stark gene: STX4 was added
gene: STX4 was added to Cardiomyopathy_Paediatric. Sources: Expert Review Amber,Literature,Literature
Mode of inheritance for gene: STX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX4 were set to 36355422; 35599850
Phenotypes for gene: STX4 were set to Deafness, autosomal recessive 123, MIM# 620745
Deafness_IsolatedAndComplex v1.332 STX4 Zornitza Stark Publications for gene: STX4 were set to 36355422
Deafness_IsolatedAndComplex v1.331 STX4 Zornitza Stark edited their review of gene: STX4: Added comment: PMID 35599850: two unrelated families were identified with biallelic STX4 variants: Family 1 with a homozygous missense c.718C>T (p.Arg240Trp) and Family 2 compound heterozygous c.89_90delGC (p.Gly30Aspfs*28) and c.232+4A>C (splice‑site). Affected individuals present with early‑onset dilated cardiomyopathy, ventricular arrhythmia, sensorineural hearing loss, global developmental delay, hypotonia and multiple congenital anomalies; the second individual died perinatally. CRISPR‑generated stx4‑null zebrafish recapitulate cardiac dysfunction, bradycardia, reduced vesicle docking and altered Ca²⁺ handling. Transgenic rescue with wild‑type stx4 restores phenotype, whereas the R241W (human R240W) allele is hypomorphic and only partially rescues, supporting a loss‑of‑function mechanism. Pharmacologic L‑type Ca²⁺ channel modulation ameliorated bradycardia, further underscoring functional loss of STX4.

Unclear if this is a separate disease association or whether it will be part of a spectrum with the previous isolated deafness reports.; Changed publications: 36355422, 35599850
Mendeliome v1.4492 SFTPA1 Lucy Spencer reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679; Phenotypes: Interstitial lung disease 1 MIM#619611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.120 Sarah Milton Added reviews for gene TDRD6 from panel Mendeliome
Mendeliome v1.4492 TDRD6 Sarah Milton reviewed gene: TDRD6: Rating: GREEN; Mode of pathogenicity: None; Publications: 39764564, 39331689, 38341271; Phenotypes: Infertility disorder, MONDO:0005047, TDRD6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.119 Sarah Milton Added reviews for gene TDRD12 from panel Mendeliome
Mendeliome v1.4492 TDRD12 Sarah Milton reviewed gene: TDRD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 40750267, 39122675; Phenotypes: Spermatogenic failure, MONDO:0004983, TDRD12-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.146 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Hereditary Spastic Paraplegia v1.146 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v1.146 SREBF2 Zornitza Stark Phenotypes for gene: SREBF2 were changed from Neurocutaneous syndrome, MONDO:0042983, SREBF2-related; Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related to Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related
Hereditary Spastic Paraplegia v1.145 SREBF2 Zornitza Stark Publications for gene: SREBF2 were set to 38847193; 39814172
Hereditary Spastic Paraplegia v1.144 SREBF2 Zornitza Stark Mode of inheritance for gene: SREBF2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.143 SREBF2 Zornitza Stark Deleted their comment
Hereditary Spastic Paraplegia v1.143 SREBF2 Zornitza Stark edited their review of gene: SREBF2: Changed publications: 39814172; Changed phenotypes: Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.143 Zornitza Stark Copied gene SREBF2 from panel Mendeliome
Hereditary Spastic Paraplegia v1.143 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Hereditary Spastic Paraplegia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SREBF2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SREBF2 were set to 38847193; 39814172
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related; Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related
Mendeliome v1.4492 SREBF2 Zornitza Stark Phenotypes for gene: SREBF2 were changed from Neurocutaneous syndrome, MONDO:0042983, SREBF2-related to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related; Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related
Mendeliome v1.4491 SREBF2 Zornitza Stark Publications for gene: SREBF2 were set to 38847193
Mendeliome v1.4490 SREBF2 Zornitza Stark Mode of inheritance for gene: SREBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4489 SREBF2 Zornitza Stark edited their review of gene: SREBF2: Added comment: PMID 39814172: reports three homozygous missense variants (p.L604W, p.T984A, p.S517F) in three unrelated families (two consanguineous families). Detailed clinical descriptions are provided for two families: Family 1 (two affected siblings, onset 39 y and 25 y, progressive spastic gait, pyramidal signs, no cognitive or peripheral neuropathy) and Family 2 (single female, onset 24 y, spastic gait, internal foot deformity, normal cognition). All carriers are asymptomatic. Functional assays in patient‑derived fibroblasts show increased mature SREBP2, cholesterol accumulation, and autophagosome/lysosome enlargement. Overexpression of the nuclear SREBP2 in Drosophila recapitulates locomotor deficits. The authors conclude that biallelic SREBF2 missense variants cause an autosomal recessive hereditary spastic paraplegia through gain‑of‑function overactivation of SREBP2.; Changed publications: 38847193, 39814172; Changed phenotypes: Neurocutaneous syndrome, MONDO:0042983, SREBF2-related, Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.630 SEC23A Zornitza Stark Classified gene: SEC23A as Amber List (moderate evidence)
Cataract v0.630 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Cataract v0.629 SEC23A Zornitza Stark edited their review of gene: SEC23A: Added comment: Two families only with each MOI.; Changed rating: AMBER; Changed phenotypes: Craniolenticulosutural dysplasia, MIM# 607812
Mendeliome v1.4489 SEC23A Zornitza Stark Publications for gene: SEC23A were set to 16980979; 21039434; 16980978; 27148587
Mendeliome v1.4488 SEC23A Zornitza Stark Mode of inheritance for gene: SEC23A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4487 SEC23A Zornitza Stark edited their review of gene: SEC23A: Changed rating: AMBER
Mendeliome v1.4487 SEC23A Zornitza Stark changed review comment from: Four families (two AR, two de novo AD) with consistent craniofacial, skeletal and ophthalmologic features. Functional data from zebrafish knock‑down.; to: Four families (two AR, two AD) with consistent craniofacial, skeletal and ophthalmologic features. Functional data from zebrafish knock‑down.
Mendeliome v1.4487 SEC23A Zornitza Stark reviewed gene: SEC23A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38275611, 37828500, 34580982; Phenotypes: Craniolenticulosutural dysplasia, MIM# 607812; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.404 REC8 Zornitza Stark Phenotypes for gene: REC8 were changed from Primary ovarian insufficiency to Infertility disorder, MONDO:0005047, REC8-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.403 REC8 Zornitza Stark reviewed gene: REC8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Infertility disorder, MONDO:0005047, REC8-related; Mode of inheritance: None
Mendeliome v1.4487 REC8 Zornitza Stark Classified gene: REC8 as Amber List (moderate evidence)
Mendeliome v1.4487 REC8 Zornitza Stark Gene: rec8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4486 TUB Krithika Murali Publications for gene: TUB were set to 24375934; 28852204
Mendeliome v1.4485 TUB Krithika Murali Phenotypes for gene: TUB were changed from Retinal dystrophy and obesity, MIM# 616188 to inherited retinal dystrophy - MONDO:0019118, TUB-related
Mendeliome v1.4484 TUB Krithika Murali Classified gene: TUB as Green List (high evidence)
Mendeliome v1.4484 TUB Krithika Murali Gene: tub has been classified as Green List (High Evidence).
Mendeliome v1.4483 TUB Krithika Murali changed review comment from: Additional unrelated individuals identified

PMID: 36650547 Xu et al 2023 report a homozygous variant (NM_003320.4, c.1379A>G, p.Asn460Ser) in an individual of Chinese ancestry with retinitis pigmentosa. No obesity

PMID: 36498982 Ziccardi et al 2022 report a homozygous splice variant in a 35 yo M of European descent with retinal dystrophy and elevated BMI.; to: Additional unrelated individuals identified

PMID: 36650547 Xu et al 2023 report a homozygous variant (NM_003320.4, c.1379A>G, p.Asn460Ser) in an individual of Chinese ancestry with retinitis pigmentosa. No obesity

PMID: 36498982 Ziccardi et al 2022 report a homozygous splice variant in a 35 yo M of European descent with retinal dystrophy and elevated BMI.
Mendeliome v1.4483 TUB Krithika Murali reviewed gene: TUB: Rating: GREEN; Mode of pathogenicity: None; Publications: 36498982, 32956375; Phenotypes: Retinal dystrophy and obesity - MIM#616188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v1.23 Sarah Milton Copied gene SVIL from panel Mendeliome
Hypertrophic cardiomyopathy v1.23 SVIL Sarah Milton gene: SVIL was added
gene: SVIL was added to Hypertrophic cardiomyopathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVIL were set to 32779703
Phenotypes for gene: SVIL were set to Myofibrillar myopathy, MIM#619040
Penetrance for gene: SVIL were set to unknown
Mendeliome v1.4483 SVIL Sarah Milton reviewed gene: SVIL: Rating: AMBER; Mode of pathogenicity: None; Publications: 39554508, 36778260, 32779703; Phenotypes: Hypertrophic cardiomyopathy MONDO:0005045, myofibrillar myopathy 10, MONDO:0033620; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4483 ITPR3 Lucy Spencer reviewed gene: ITPR3: Rating: RED; Mode of pathogenicity: None; Publications: 36302985; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.145 ITPR3 Lucy Spencer reviewed gene: ITPR3: Rating: RED; Mode of pathogenicity: None; Publications: 36302985; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4483 OXGR1 Rylee Peters reviewed gene: OXGR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36571463; Phenotypes: Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.687 TRAPPC2L Krithika Murali Phenotypes for gene: TRAPPC2L were changed from Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related to Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related
Intellectual disability syndromic and non-syndromic v1.686 TRAPPC2L Krithika Murali Phenotypes for gene: TRAPPC2L were changed from Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331 to Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related
Intellectual disability syndromic and non-syndromic v1.686 TRAPPC2L Krithika Murali Publications for gene: TRAPPC2L were set to 36849228; 32843486; 30120216
Intellectual disability syndromic and non-syndromic v1.685 TRAPPC2L Krithika Murali Publications for gene: TRAPPC2L were set to 30120216; 32843486
Intellectual disability syndromic and non-syndromic v1.685 TRAPPC2L Krithika Murali Classified gene: TRAPPC2L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.685 TRAPPC2L Krithika Murali Gene: trappc2l has been classified as Green List (High Evidence).
Mendeliome v1.4483 TRAPPC2L Krithika Murali Phenotypes for gene: TRAPPC2L were changed from Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331 to Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related
Mendeliome v1.4482 TRAPPC2L Krithika Murali Publications for gene: TRAPPC2L were set to 30120216; 32843486
Intellectual disability syndromic and non-syndromic v1.684 Krithika Murali Added reviews for gene TRAPPC2L from panel Mendeliome
Mendeliome v1.4481 TRAPPC2L Krithika Murali Classified gene: TRAPPC2L as Green List (high evidence)
Mendeliome v1.4481 TRAPPC2L Krithika Murali Gene: trappc2l has been classified as Green List (High Evidence).
Mendeliome v1.4480 TRAPPC2L Krithika Murali reviewed gene: TRAPPC2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 36849228, 32843486, 30120216; Phenotypes: Neurodevelopmental disorder - MONDO:0700092, TRAPPC2L-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4480 REC8 Zornitza Stark changed review comment from: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with homozygous missense.; to: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with het missense with relatively high pop frequency, discounted.
Mendeliome v1.4480 REC8 Zornitza Stark edited their review of gene: REC8: Changed rating: AMBER
Infertility and Recurrent Pregnancy Loss v1.118 REC8 Zornitza Stark Classified gene: REC8 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.118 REC8 Zornitza Stark Gene: rec8 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.117 REC8 Zornitza Stark edited their review of gene: REC8: Changed rating: AMBER
Infertility and Recurrent Pregnancy Loss v1.117 REC8 Zornitza Stark changed review comment from: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with homozygous missense.; to: PMID 35172124 reports homozygous frameshift deletion presenting with non‑obstructive azoospermia and meiotic arrest in a single affected individual. Further individual in PMID 31479588, but with heterozygous missense with high pop frequency.
Mendeliome v1.4480 REC8 Zornitza Stark Phenotypes for gene: REC8 were changed from Primary ovarian insufficiency to Infertility disorder, MONDO:0005047, REC8-related
Mendeliome v1.4479 REC8 Zornitza Stark Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Mendeliome v1.4478 REC8 Zornitza Stark Classified gene: REC8 as Green List (high evidence)
Mendeliome v1.4478 REC8 Zornitza Stark Gene: rec8 has been classified as Green List (High Evidence).
Mendeliome v1.4477 REC8 Zornitza Stark reviewed gene: REC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35172124, 31479588; Phenotypes: Infertility disorder, MONDO:0005047, REC8-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.117 REC8 Zornitza Stark Marked gene: REC8 as ready
Infertility and Recurrent Pregnancy Loss v1.117 REC8 Zornitza Stark Gene: rec8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.117 REC8 Zornitza Stark Phenotypes for gene: REC8 were changed from Primary ovarian insufficiency to Infertility disorder, MONDO:0005047, REC8-related
Infertility and Recurrent Pregnancy Loss v1.116 REC8 Zornitza Stark Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Infertility and Recurrent Pregnancy Loss v1.115 REC8 Zornitza Stark Classified gene: REC8 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.115 REC8 Zornitza Stark Gene: rec8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.114 REC8 Zornitza Stark reviewed gene: REC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35172124, 31479588; Phenotypes: Infertility disorder, MONDO:0005047, REC8-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Arterial Hypertension v1.55 Sarah Milton Copied Region FOXF1 upstream regulatory region from panel Mendeliome
Pulmonary Arterial Hypertension v1.55 FOXF1 upstream regulatory region Sarah Milton Region: FOXF1 upstream regulatory region was added
Region: FOXF1 upstream regulatory region was added to Pulmonary Arterial Hypertension. Sources: Literature
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
Mendeliome v1.4477 FOXF1 upstream regulatory region Sarah Milton Variant type for FOXF1 upstream regulatory region was changed from small to cnv_loss.
Mendeliome v1.4476 FOXF1 upstream regulatory region Sarah Milton Region: FOXF1 upstream regulatory region was added
Region: FOXF1 upstream regulatory region was added to Mendeliome. Sources: Literature
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
Review for Region: FOXF1 upstream regulatory region was set to GREEN
Added comment: FOXF1 is a transcription factor involved in maintaining endothelial barrier through activation of S1P/S1PR1 signalling for integrity of adherens junctions.

An approximately 60kb enhancer 270kb upstream of the FOXF1 gene has been identified with copy number changes in this region seen in over 10 affected individuals with biopsy confirmed alveolar capillary dysplasia with misalignment of pulmonary veins.
Interestingly a large number of the deletions identified were de novo on the maternal allele.

Deletion size ranged between 104kb to 2625kb, coordinates from this entry are from a minimal overlapping region.

The enhancer region has binding motifs for a number of transcription factors, as well as this there is a non coding RNA (LINC01081) within the region that is thought to play a role with regulation of FOXF1 transcription. Supportive functional studies with RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level.
Sources: Literature
Mendeliome v1.4475 SLC13A1 Lucy Spencer Publications for gene: SLC13A1 were set to 36175384
Mendeliome v1.4474 RHOXF1 Lucy Spencer reviewed gene: RHOXF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28171600; Phenotypes: Spermatogenic failure, MONDO:0004983, RHOXF1-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuria v0.236 Lucy Spencer Added reviews for gene PRDM15 from panel Mendeliome
Microcephaly v1.417 Lucy Spencer Copied gene PRDM15 from panel Mendeliome
Microcephaly v1.417 PRDM15 Lucy Spencer gene: PRDM15 was added
gene: PRDM15 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080
Phenotypes for gene: PRDM15 were set to Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Holoprosencephaly and septo-optic dysplasia v1.24 Lucy Spencer Added reviews for gene PRDM15 from panel Mendeliome
Fetal anomalies v1.542 Lucy Spencer Added reviews for gene PRDM15 from panel Mendeliome
Anophthalmia_Microphthalmia_Coloboma v1.57 Lucy Spencer Copied gene PRDM15 from panel Mendeliome
Anophthalmia_Microphthalmia_Coloboma v1.57 PRDM15 Lucy Spencer gene: PRDM15 was added
gene: PRDM15 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080
Phenotypes for gene: PRDM15 were set to Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Mendeliome v1.4474 PRDM15 Lucy Spencer Phenotypes for gene: PRDM15 were changed from Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related; Galloway-Mowat syndrome MONDO:0009627, PRDM15-related to Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Mendeliome v1.4473 PRDM15 Lucy Spencer reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 31950080, 33593823; Phenotypes: Galloway-Mowat syndrome MONDO:0009627, PRDM15-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4473 PRDM15 Lucy Spencer Deleted their review
Mendeliome v1.4473 PRDM15 Lucy Spencer changed review comment from: PMID: 33593823- Reports the same families as PMID:31950080. 4 families homozygous for C844Y who had syndromic SRNS which this paper described as Galloway-Mowat syndrome, and another 2 homozygous for M154K or E190K who had isolated SRNS. Paper suggests the more severe phenotype associated with C844Y is because it affects a Cys residue in a zinc finger domain and was shown to destabilize the protein while also interfering with transcriptional activity while the other 2 missense in the SET domain decrease protein stability but do not affect transcriptional activity. In knock-out cell lines pronephric development was disrupted and could be rescued by WT but not by any of the 3 patient missense variants.

Borderline amber/green; to: PMID: 33593823- Reports the same families as PMID:31950080. 4 families homozygous for C844Y who had syndromic SRNS which this paper described as Galloway-Mowat syndrome, and another 2 homozygous for M154K or E190K who had isolated SRNS. Paper suggests the more severe phenotype associated with C844Y is because it affects a Cys residue in a zinc finger domain and was shown to destabilize the protein while also interfering with transcriptional activity while the other 2 missense in the SET domain decrease protein stability but do not affect transcriptional activity. In knock-out cell lines pronephric development was disrupted and could be rescued by WT but not by any of the 3 patient missense variants.

Borderline amber/green, likely 1 spectrum of disease
Mendeliome v1.4473 PRDM15 Lucy Spencer Phenotypes for gene: PRDM15 were changed from Multiple congenital anomalies MONDO:0019042, PRDM15-related to Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related; Galloway-Mowat syndrome MONDO:0009627, PRDM15-related
Mendeliome v1.4472 PRDM15 Lucy Spencer Classified gene: PRDM15 as Green List (high evidence)
Mendeliome v1.4472 PRDM15 Lucy Spencer Gene: prdm15 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.381 ATP11A Lucy Spencer Publications for gene: ATP11A were set to 40185629
Genetic Epilepsy v1.380 ATP11A Lucy Spencer Phenotypes for gene: ATP11A were changed from Focal Epilepsy MONDO:0005384 to Focal epilepsy MONDO:0005384, ATP11A; Leukodystrophy, hypomyelinating, 24 MIM#619851
Genetic Epilepsy v1.379 ATP11A Lucy Spencer Classified gene: ATP11A as Green List (high evidence)
Genetic Epilepsy v1.379 ATP11A Lucy Spencer Gene: atp11a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.378 ATP11A Lucy Spencer reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34403372, 39432785, 40185629; Phenotypes: Focal epilepsy MONDO:0005384, ATP11A, Leukodystrophy, hypomyelinating, 24 MIM#619851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4471 PRDM15 Lucy Spencer reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33593823, 31950080; Phenotypes: Steroid-resistant nephrotic syndrome MONDO:0044765, PRDM15-related, Galloway-Mowat syndrome MONDO:0009627, PRDM15-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.683 PPP1R15B Lucy Spencer Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Intellectual disability syndromic and non-syndromic v1.682 PPP1R15B Lucy Spencer Classified gene: PPP1R15B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.682 PPP1R15B Lucy Spencer Gene: ppp1r15b has been classified as Green List (High Evidence).
Microcephaly v1.416 PPP1R15B Lucy Spencer Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Microcephaly v1.415 PPP1R15B Lucy Spencer Classified gene: PPP1R15B as Green List (high evidence)
Microcephaly v1.415 PPP1R15B Lucy Spencer Gene: ppp1r15b has been classified as Green List (High Evidence).
Microcephaly v1.414 Lucy Spencer Added reviews for gene PPP1R15B from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.681 Lucy Spencer Added reviews for gene PPP1R15B from panel Mendeliome
Mendeliome v1.4471 PPP1R15B Lucy Spencer Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Mendeliome v1.4470 PPP1R15B Lucy Spencer Classified gene: PPP1R15B as Green List (high evidence)
Mendeliome v1.4470 PPP1R15B Lucy Spencer Gene: ppp1r15b has been classified as Green List (High Evidence).
Mendeliome v1.4469 PPP1R15B Lucy Spencer reviewed gene: PPP1R15B: Rating: GREEN; Mode of pathogenicity: None; Publications: 38159565, 26159176, 26307080, 27640355, 40568171; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 2, MIM#616817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v1.32 TRAF3IP2 Krithika Murali Publications for gene: TRAF3IP2 were set to 34289170; 33825088; 33359359; 32350852; 31292894; 30237576; 28640246
Defects of intrinsic and innate immunity v1.32 TRAF3IP2 Krithika Murali Classified gene: TRAF3IP2 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.32 TRAF3IP2 Krithika Murali Gene: traf3ip2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.31 TRAF3IP2 Krithika Murali Publications for gene: TRAF3IP2 were set to 24120361; 31292894; 20660351
Defects of intrinsic and innate immunity v1.31 TRAF3IP2 Krithika Murali Classified gene: TRAF3IP2 as Green List (high evidence)
Defects of intrinsic and innate immunity v1.31 TRAF3IP2 Krithika Murali Gene: traf3ip2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.31 Krithika Murali Added reviews for gene TRAF3IP2 from panel Mendeliome
Defects of intrinsic and innate immunity v1.30 Krithika Murali Added reviews for gene TRAF3IP2 from panel Mendeliome
Disorders of immune dysregulation v1.38 Krithika Murali Copied gene TRAF3IP2 from panel Mendeliome
Disorders of immune dysregulation v1.38 TRAF3IP2 Krithika Murali gene: TRAF3IP2 was added
gene: TRAF3IP2 was added to Disorders of immune dysregulation. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAF3IP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAF3IP2 were set to 24120361; 31292894; 20660351; 34289170; 33825088; 33359359; 32350852; 31292894; 30237576; 28640246
Phenotypes for gene: TRAF3IP2 were set to Candidiasis, familial, 8, MIM# 615527
Disorders of immune dysregulation v1.38 Krithika Murali Copied gene TRAF3IP2 from panel Mendeliome
Disorders of immune dysregulation v1.38 TRAF3IP2 Krithika Murali gene: TRAF3IP2 was added
gene: TRAF3IP2 was added to Disorders of immune dysregulation. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAF3IP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAF3IP2 were set to 24120361; 31292894; 20660351; 34289170; 33825088; 33359359; 32350852; 31292894; 30237576; 28640246
Phenotypes for gene: TRAF3IP2 were set to Candidiasis, familial, 8, MIM# 615527
Mendeliome v1.4469 TRAF3IP2 Krithika Murali Publications for gene: TRAF3IP2 were set to 24120361; 31292894; 20660351
Mendeliome v1.4468 TRAF3IP2 Krithika Murali Classified gene: TRAF3IP2 as Green List (high evidence)
Mendeliome v1.4468 TRAF3IP2 Krithika Murali Gene: traf3ip2 has been classified as Green List (High Evidence).
Mendeliome v1.4467 TRAF3IP2 Krithika Murali reviewed gene: TRAF3IP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34289170, 33825088, 33359359, 32350852, 31292894, 30237576, 28640246; Phenotypes: candidiasis, familial, 8, MONDO:0014230, ?Candidiasis, familial, 8 - MIM#615527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.145 TRAC Krithika Murali Phenotypes for gene: TRAC were changed from Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387 to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387; TCR-alpha-beta-positive T-cell deficiency, MONDO:0014160
Combined Immunodeficiency v1.144 TRAC Krithika Murali Publications for gene: TRAC were set to 21206088
Combined Immunodeficiency v1.144 TRAC Krithika Murali Classified gene: TRAC as Green List (high evidence)
Combined Immunodeficiency v1.144 TRAC Krithika Murali Gene: trac has been classified as Green List (High Evidence).
Mendeliome v1.4467 TRAC Krithika Murali Phenotypes for gene: TRAC were changed from Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387 to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387; TCR-alpha-beta-positive T-cell deficiency, MONDO:0014160
Mendeliome v1.4466 TRAC Krithika Murali Publications for gene: TRAC were set to 21206088
Mendeliome v1.4465 TRAC Krithika Murali Classified gene: TRAC as Green List (high evidence)
Mendeliome v1.4465 TRAC Krithika Murali Gene: trac has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.143 Krithika Murali Added reviews for gene TRAC from panel Mendeliome
Mendeliome v1.4464 TRAC Krithika Murali reviewed gene: TRAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 41103553, 33909184; Phenotypes: TCR-alpha-beta-positive T-cell deficiency, MONDO:0014160, Immunodeficiency 7, TCR-alpha/beta deficient 615387; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4464 TPCN2 Krithika Murali Phenotypes for gene: TPCN2 were changed from [Skin/hair/eye pigmentation 10, blond/brown hair] MIM#612267 to albinism, TPCN2-related - MONDO:0043209
Ocular and Oculocutaneous Albinism v1.15 TPCN2 Krithika Murali Phenotypes for gene: TPCN2 were changed from Hypopigmentation of the skin MONDO:0019290 to albinism, TPCN2-related - MONDO:0043209
Ocular and Oculocutaneous Albinism v1.14 TPCN2 Krithika Murali Publications for gene: TPCN2 were set to 36641477; 3980994
Ocular and Oculocutaneous Albinism v1.14 TPCN2 Krithika Murali Publications for gene: TPCN2 were set to 36641477
Ocular and Oculocutaneous Albinism v1.13 Krithika Murali Added reviews for gene TPCN2 from panel Mendeliome
Mendeliome v1.4463 TPCN2 Krithika Murali reviewed gene: TPCN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 39809949, 36641477; Phenotypes: albinism, MONDO:0043209; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4463 EXOSC10 Sangavi Sivagnanasundram reviewed gene: EXOSC10: Rating: AMBER; Mode of pathogenicity: None; Publications: 41609100; Phenotypes: premature ovarian insufficiency MONDO:0019852; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v1.43 ERBB4 Sangavi Sivagnanasundram edited their review of gene: ERBB4: Changed publications: 31432357, 32638105, 33414559, 35873773, 38291418; Changed phenotypes: amyotrophic lateral sclerosis type 19, MONDO:0014223
Motor Neurone Disease v1.43 ERBB4 Sangavi Sivagnanasundram changed review comment from: Update to GDA and publications

GREEN association for ALS - 6 other unrelated individuals reported with ALS and heterozygous variants in ERBB4 (PMID: 31432357, 32638105, 33414559, 35873773, 38291418)

RED for Hirschsprung - only one affected individual identified (PMID: 29483666)
RED for idiopathic hypogonadotropic hypogonadism (IHH) - only one affected individual identified (PMID: 36123965); to: Update to GDA and publications

GREEN association for ALS - 6 other unrelated individuals reported with ALS and heterozygous variants in ERBB4 (PMID: 31432357, 32638105, 33414559, 35873773, 38291418)
Motor Neurone Disease v1.43 Sangavi Sivagnanasundram Added reviews for gene ERBB4 from panel Mendeliome
Mendeliome v1.4463 ERBB4 Sangavi Sivagnanasundram reviewed gene: ERBB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38291418, 36123965, 35873773, 33414559, 32638105, 31432357, 29483666; Phenotypes: amyotrophic lateral sclerosis type 19, MONDO:0014223, Hirschsprung disease MONDO:0018309, idiopathic hypogonadotropic hypogonadism MONDO:0018555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.541 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Fetal anomalies v1.540 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.417 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Skeletal dysplasia v0.416 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v1.30 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Severe Combined Immunodeficiency v1.29 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4463 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230,DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Mendeliome v1.4462 DMRT2 Zornitza Stark edited their review of gene: DMRT2: Changed rating: GREEN
Mendeliome v1.4462 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.529 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Congenital Heart Defect v0.528 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.201 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.200 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.246 DMRT2 Zornitza Stark Phenotypes for gene: DMRT2 were changed from skeletal dysplasia MONDO:0018230; DMRT2-related to Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523
Skeletal Dysplasia_Fetal v0.245 DMRT2 Zornitza Stark reviewed gene: DMRT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 7, autosomal recessive, MIM# 621523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.606 ATP2B3 Bryony Thompson Classified gene: ATP2B3 as Green List (high evidence)
Regression v0.606 ATP2B3 Bryony Thompson Gene: atp2b3 has been classified as Green List (High Evidence).
Ataxia v1.190 ATP2B3 Bryony Thompson Publications for gene: ATP2B3 were set to
Ataxia v1.189 ATP2B3 Bryony Thompson Classified gene: ATP2B3 as Green List (high evidence)
Ataxia v1.189 ATP2B3 Bryony Thompson Gene: atp2b3 has been classified as Green List (High Evidence).
Ataxia v1.188 Bryony Thompson Added reviews for gene ATP2B3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.680 ATP2B3 Bryony Thompson Classified gene: ATP2B3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.680 ATP2B3 Bryony Thompson Gene: atp2b3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.679 ATP2B3 Bryony Thompson edited their review of gene: ATP2B3: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.679 ATP2B3 Bryony Thompson changed review comment from: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).; to: At least 3 cases reported with ID/developmental delay without other variants detected
PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).
Intellectual disability syndromic and non-syndromic v1.679 ATP2B3 Bryony Thompson edited their review of gene: ATP2B3: Changed rating: AMBER
Ataxia v1.187 ATP2B3 Bryony Thompson Deleted their review
Regression v0.605 Bryony Thompson Added reviews for gene ATP2B3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.679 Bryony Thompson Added reviews for gene ATP2B3 from panel Mendeliome
Ataxia v1.186 ATP2B3 Bryony Thompson Deleted their comment
Ataxia v1.187 Bryony Thompson Added reviews for gene ATP2B3 from panel Mendeliome
Mendeliome v1.4462 ATP2B3 Bryony Thompson changed review comment from: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).; to: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).
Mendeliome v1.4462 ATP2B3 Bryony Thompson Deleted their comment
Mendeliome v1.4462 ATP2B3 Bryony Thompson Classified gene: ATP2B3 as Green List (high evidence)
Mendeliome v1.4462 ATP2B3 Bryony Thompson Gene: atp2b3 has been classified as Green List (High Evidence).
Mendeliome v1.4461 ATP2B3 Bryony Thompson Publications for gene: ATP2B3 were set to 22912398; 27653636; 27632770
Mendeliome v1.4460 ATP2B3 Bryony Thompson edited their review of gene: ATP2B3: Added comment: PMIDs 25953895, 27653636, 28807751, 36207321 and 37821930 report 11 patients from 8 unrelated families with hemizygous ATP2B3 missense variants causing early‑onset cerebellar ataxia, hypotonia, developmental delay and sometimes seizures or dystonia. 2 of the patients had alternate diagnoses in PMM2 & LAMA1. Functional studies (HeLa Ca2+ assays, yeast complementation, homology modelling) demonstrate loss‑of‑function or altered pump activity. Single reports also link ATP2B3 to autism (PMID 28720891) and fetal akinesia (PMID 31680123).; Changed rating: GREEN; Changed publications: 37821930, 36207321, 31680123, 28807751, 28720891, 27653636, 25953895; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, Syndromic disease, MONDO:0002254, X-linked progressive cerebellar ataxia, MONDO:0010547; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.4460 ARPC3 Bryony Thompson Publications for gene: ARPC3 were set to 36928819; 26166300
Pulmonary Arterial Hypertension v1.54 AQP1 Bryony Thompson Classified gene: AQP1 as Green List (high evidence)
Pulmonary Arterial Hypertension v1.54 AQP1 Bryony Thompson Gene: aqp1 has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.53 Bryony Thompson Added reviews for gene AQP1 from panel Mendeliome
Mendeliome v1.4459 AQP1 Bryony Thompson Classified gene: AQP1 as Green List (high evidence)
Mendeliome v1.4459 AQP1 Bryony Thompson Gene: aqp1 has been classified as Green List (High Evidence).
Mendeliome v1.4458 AQP1 Bryony Thompson reviewed gene: AQP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40229839, 37007933, 35811711, 35627312, 35346192, 29650961; Phenotypes: pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.4458 EXOC8 Zornitza Stark Marked gene: EXOC8 as ready
Mendeliome v1.4458 EXOC8 Zornitza Stark Gene: exoc8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.678 EXOC8 Zornitza Stark Marked gene: EXOC8 as ready
Intellectual disability syndromic and non-syndromic v1.678 EXOC8 Zornitza Stark Gene: exoc8 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.59 EMD Zornitza Stark Publications for gene: EMD were set to 24997722
Dilated Cardiomyopathy v1.58 EMD Zornitza Stark edited their review of gene: EMD: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dilated Cardiomyopathy v1.58 EMD Zornitza Stark Classified gene: EMD as Green List (high evidence)
Dilated Cardiomyopathy v1.58 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.57 EMD Zornitza Stark changed review comment from: Multiple reports of isolated DCM, including pedigrees with extensive segregation. The p.Val26Ala variant is reported in multiple individuals.; to: Multiple reports of isolated DCM, including pedigrees with extensive segregation. The p.Val26Ala variant is reported in multiple individuals from the Canary Islands ?founder.
Dilated Cardiomyopathy v1.57 EMD Zornitza Stark reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 18266676, 24997722, 32755394, 38337354, 40065010; Phenotypes: Cardiomyopathy, dilated, 3C, MIM# 301163; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoimmune Lymphoproliferative Syndrome v1.12 CASP10 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen due to relatively high pop frequency of some of the missense variants.
Autoimmune Lymphoproliferative Syndrome v1.12 CASP10 Zornitza Stark Classified gene: CASP10 as Amber List (moderate evidence)
Autoimmune Lymphoproliferative Syndrome v1.12 CASP10 Zornitza Stark Gene: casp10 has been classified as Amber List (Moderate Evidence).
Autoimmune Lymphoproliferative Syndrome v1.11 CASP10 Zornitza Stark reviewed gene: CASP10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4458 CASP10 Zornitza Stark Classified gene: CASP10 as Amber List (moderate evidence)
Mendeliome v1.4458 CASP10 Zornitza Stark Gene: casp10 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v1.37 CASP10 Zornitza Stark Classified gene: CASP10 as Amber List (moderate evidence)
Disorders of immune dysregulation v1.37 CASP10 Zornitza Stark Gene: casp10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.540 GRK2 Zornitza Stark Publications for gene: GRK2 were set to 33200460
Fetal anomalies v1.539 GRK2 Zornitza Stark Classified gene: GRK2 as Green List (high evidence)
Fetal anomalies v1.539 GRK2 Zornitza Stark Gene: grk2 has been classified as Green List (High Evidence).
Fetal anomalies v1.538 GRK2 Zornitza Stark reviewed gene: GRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38647386; Phenotypes: Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Ciliopathies v1.23 GRK2 Zornitza Stark Publications for gene: GRK2 were set to 33200460
Skeletal Ciliopathies v1.22 GRK2 Zornitza Stark Classified gene: GRK2 as Green List (high evidence)
Skeletal Ciliopathies v1.22 GRK2 Zornitza Stark Gene: grk2 has been classified as Green List (High Evidence).
Skeletal Ciliopathies v1.21 GRK2 Zornitza Stark edited their review of gene: GRK2: Added comment: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.; Changed rating: GREEN; Changed publications: 33200460, 38647386
Ciliopathies v1.99 GRK2 Zornitza Stark Publications for gene: GRK2 were set to 33200460
Ciliopathies v1.98 GRK2 Zornitza Stark Classified gene: GRK2 as Green List (high evidence)
Ciliopathies v1.98 GRK2 Zornitza Stark Gene: grk2 has been classified as Green List (High Evidence).
Mendeliome v1.4457 GRK2 Zornitza Stark Publications for gene: GRK2 were set to 33200460
Ciliopathies v1.97 GRK2 Zornitza Stark edited their review of gene: GRK2: Added comment: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.; Changed rating: GREEN; Changed publications: 33200460, 38647386
Mendeliome v1.4456 GRK2 Zornitza Stark Classified gene: GRK2 as Green List (high evidence)
Mendeliome v1.4456 GRK2 Zornitza Stark Gene: grk2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.114 Zornitza Stark Copied gene REC8 from panel Primary Ovarian Insufficiency_Premature Ovarian Failure
Infertility and Recurrent Pregnancy Loss v1.114 REC8 Zornitza Stark gene: REC8 was added
gene: REC8 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: REC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Phenotypes for gene: REC8 were set to Primary ovarian insufficiency
Mendeliome v1.4455 GRK2 Teresa Zhao changed review comment from: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.; to: PMID 38647386 (2024): a novel homozygous p.(Arg474Ter) reported in an individual with Jeune ATD. Both parents are healthy carriers. Additional features include Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and mid-gut malrotation. Same patient has been reported again in PMID: 38585547.
Fetal anomalies v1.538 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Fetal anomalies v1.537 PPP1R12A Zornitza Stark reviewed gene: PPP1R12A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Genitourinary and/or/brain malformation syndrome MIM#618820; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.678 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Intellectual disability syndromic and non-syndromic v1.677 PPP1R12A Zornitza Stark edited their review of gene: PPP1R12A: Changed phenotypes: Genitourinary and/or/brain malformation syndrome MIM#618820
Holoprosencephaly and septo-optic dysplasia v1.23 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Holoprosencephaly and septo-optic dysplasia v1.22 PPP1R12A Zornitza Stark edited their review of gene: PPP1R12A: Changed phenotypes: Genitourinary and/or/brain malformation syndrome MIM#618820
Differences of Sex Development v1.44 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Differences of Sex Development v1.43 PPP1R12A Zornitza Stark edited their review of gene: PPP1R12A: Changed phenotypes: Genitourinary and/or/brain malformation syndrome MIM#618820
Mendeliome v1.4455 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from Intellectual disability; holoprosencephaly; disorder of sex development to Genitourinary and/or/brain malformation syndrome MIM#618820
Mendeliome v1.4454 MCAT Rylee Peters reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 36881526, 33918393, 31915829; Phenotypes: Optic atrophy 15, MIM# 620583, Mitochondrial disease (MONDO:0044970), MCAT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4454 GRK2 Teresa Zhao reviewed gene: GRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38647386; Phenotypes: Jeune asphyxiating thoracic dystrophy (ATD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4454 CASP10 Chern Lim reviewed gene: CASP10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune lymphoproliferative syndrome, type II, MIM#603909; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Disorders of immune dysregulation v1.36 CASP10 Chern Lim reviewed gene: CASP10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune lymphoproliferative syndrome, type II, MIM#603909; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hereditary Neuropathy v1.182 PMP22 Zornitza Stark Marked gene: PMP22 as ready
Hereditary Neuropathy v1.182 PMP22 Zornitza Stark Gene: pmp22 has been classified as Green List (High Evidence).
Hereditary Neuropathy v1.182 PMP22 Zornitza Stark Phenotypes for gene: PMP22 were changed from Charcot Marie Tooth disease, type 1A, 118220; Roussy Levy syndrome, 180800; Neuropathy, inflammatory demyelinating, 139393; Neuropathy, recurrent, with pressure palsies, 162500; Charcot Marie Tooth disease, type 1E, 118300; Dejerine Sottas disease, 145900; HMSN to Charcot-Marie-Tooth disease, type 1A, MIM# 118220; Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Dejerine-Sottas disease, MIM# 145900; Neuropathy, recurrent, with pressure palsies 162500; Roussy-Levy syndrome 180800
Hereditary Neuropathy v1.181 PMP22 Zornitza Stark Publications for gene: PMP22 were set to
Hereditary Neuropathy v1.180 PMP22 Zornitza Stark Mode of inheritance for gene: PMP22 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v1.179 PMP22 Zornitza Stark edited their review of gene: PMP22: Added comment: Addition of studies to support GREEN AR GDA with PMP22. The reported affected individuals present with infantile/early-onset CMT/ Dejerine‑Sottas disease (which is now known as CMT type 3).

AD GDA (GREEN)
Classified as Definitive ClinGen CMT GCEP in association with Charcot-Marie-Tooth disease type 1A - https://search.clinicalgenome.org/CCID:005837

Classified as Definitive by ClinGen CMT GCEp in association with hereditary neuropathy with liability to pressure palsies - https://search.clinicalgenome.org/CCID:008314; Changed publications: 32412171, 31777123, 32719652; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4454 PMP22 Zornitza Stark Publications for gene: PMP22 were set to 32356557
Mendeliome v1.4453 PMP22 Zornitza Stark Mode of inheritance for gene: PMP22 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Incidentalome v0.430 RBM12 Zornitza Stark Phenotypes for gene: RBM12 were changed from to Schizophrenia 19 (MIM#617629)
Incidentalome v0.429 RBM12 Zornitza Stark reviewed gene: RBM12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Schizophrenia 19 (MIM#617629); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4452 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231; 37448355
Mendeliome v1.4451 PTPA Zornitza Stark edited their review of gene: PTPA: Added comment: Further family reported in PMID 37046398 with homozygous missense and early onset PD; however, variant is hmz missense with no supportive data.; Changed publications: 36073231, 37046398
Early-onset Parkinson disease v2.50 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231; 37448355
Early-onset Parkinson disease v2.49 PTPA Zornitza Stark edited their review of gene: PTPA: Added comment: Further family reported in PMID 37046398 with homozygous missense and early onset PD; however, variant is hmz missense with no supportive data.; Changed publications: 36073231, 37046398
Fetal anomalies v1.537 NEK9 Zornitza Stark Classified gene: NEK9 as Green List (high evidence)
Fetal anomalies v1.537 NEK9 Zornitza Stark Gene: nek9 has been classified as Green List (High Evidence).
Fetal anomalies v1.536 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: Three more families reported with milder phenotypes, but still a range of abnormalities that are potentially detectable on fetal US.; Changed rating: GREEN; Changed publications: 26908619, 21271645, 36712877
Multiple pterygium syndrome_Fetal akinesia sequence v1.11 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619
Multiple pterygium syndrome_Fetal akinesia sequence v1.10 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: Another 2 families reported in PMID 36712877 but again with milder arthrogryposis, retain Amber rating on this panel.; Changed publications: 26908619, 21271645, 36712877
Arthrogryposis v1.16 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619; 21271645
Arthrogryposis v1.15 NEK9 Zornitza Stark edited their review of gene: NEK9: Changed publications: 36712877, 26908619, 21271645
Arthrogryposis v1.15 NEK9 Zornitza Stark Classified gene: NEK9 as Green List (high evidence)
Arthrogryposis v1.15 NEK9 Zornitza Stark Gene: nek9 has been classified as Green List (High Evidence).
Arthrogryposis v1.14 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: PMID 36712877: 2 more families reported with neonatal arthrogryposis, contractures, camptodactyly, atrial septal defect, mild pulmonary stenosis, and pyloric stenosis; biallelic LoF variants.

The reported disease entities appear to represent a spectrum of disease.; Changed rating: GREEN
Skeletal Dysplasia_Fetal v0.245 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619
Skeletal Dysplasia_Fetal v0.244 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: Three more families reported but with milder phenotypes and post-natal presentation, retain Red rating on this panel.; Changed publications: 26908619, 21271645, 36712877; Changed phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia
Mendeliome v1.4451 NEK9 Zornitza Stark Publications for gene: NEK9 were set to 26908619; 21271645
Mendeliome v1.4450 NEK9 Zornitza Stark Classified gene: NEK9 as Green List (high evidence)
Mendeliome v1.4450 NEK9 Zornitza Stark Gene: nek9 has been classified as Green List (High Evidence).
Mendeliome v1.4449 NEK9 Zornitza Stark edited their review of gene: NEK9: Added comment: PMID 36712877: 2 more families reported with neonatal arthrogryposis, contractures, camptodactyly, atrial septal defect, mild pulmonary stenosis, and pyloric stenosis; biallelic LoF variants.; Changed rating: GREEN; Changed publications: 26908619, 21271645, 36712877
Pituitary hormone deficiency v0.176 NDNF Zornitza Stark Mode of inheritance for gene: NDNF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.175 NDNF Zornitza Stark edited their review of gene: NDNF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.175 NDNF Zornitza Stark edited their review of gene: NDNF: Added comment: PMID 36454653: another individual with homozygous LoF variant and Kallman syndrome.; Changed publications: 31883645, 40788466, 36454653; Changed phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Hypogonadotropic hypogonadism v0.82 NDNF Zornitza Stark Marked gene: NDNF as ready
Hypogonadotropic hypogonadism v0.82 NDNF Zornitza Stark Gene: ndnf has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism v0.82 NDNF Zornitza Stark Publications for gene: NDNF were set to 31883645; 40788466
Hypogonadotropic hypogonadism v0.81 NDNF Zornitza Stark Mode of inheritance for gene: NDNF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v0.80 NDNF Zornitza Stark edited their review of gene: NDNF: Added comment: PMID 36454653: another individual with homozygous LoF variant and Kallman syndrome.; Changed publications: 31883645, 40788466, 36454653; Changed phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v1.43 NDNF Zornitza Stark Publications for gene: NDNF were set to 31883645; 40788466
Differences of Sex Development v1.42 NDNF Zornitza Stark Mode of inheritance for gene: NDNF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v1.41 NDNF Zornitza Stark edited their review of gene: NDNF: Changed phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Differences of Sex Development v1.41 NDNF Zornitza Stark edited their review of gene: NDNF: Added comment: PMID 36454653: another individual with homozygous LoF variant and Kallman syndrome.; Changed publications: 31883645, 40788466, 36454653; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4449 NDNF Zornitza Stark Publications for gene: NDNF were set to 31883645; 40788466
Mendeliome v1.4448 NDNF Zornitza Stark Mode of inheritance for gene: NDNF was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4447 NDNF Zornitza Stark edited their review of gene: NDNF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4447 NDNF Zornitza Stark edited their review of gene: NDNF: Added comment: PMID 36454653: another individual with homozygous LoF variant and Kallman syndrome.; Changed publications: 31883645, 40788466, 36454653; Changed phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Mendeliome v1.4447 NAV2 Zornitza Stark Phenotypes for gene: NAV2 were changed from Developmental delay; cerebellar hypoplasia; cerebellar dysplasia to Neurodevelopmental disorder, MONDO:0700092, NAV2-related
Mendeliome v1.4446 NAV2 Zornitza Stark reviewed gene: NAV2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NAV2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.677 NAV2 Zornitza Stark Marked gene: NAV2 as ready
Intellectual disability syndromic and non-syndromic v1.677 NAV2 Zornitza Stark Gene: nav2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.677 NAV2 Zornitza Stark Phenotypes for gene: NAV2 were changed from Developmental delay; cerebellar hypoplasia; cerebellar dysplasia to Neurodevelopmental disorder, MONDO:0700092, NAV2-related
Intellectual disability syndromic and non-syndromic v1.676 NAV2 Zornitza Stark reviewed gene: NAV2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, NAV2-related; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.676 Zornitza Stark Copied gene NAV2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.676 NAV2 Zornitza Stark gene: NAV2 was added
gene: NAV2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NAV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV2 were set to PMID:35218524
Phenotypes for gene: NAV2 were set to Developmental delay; cerebellar hypoplasia; cerebellar dysplasia
Intellectual disability syndromic and non-syndromic v1.675 RSF1 Rylee Peters Marked gene: RSF1 as ready
Intellectual disability syndromic and non-syndromic v1.675 RSF1 Rylee Peters Gene: rsf1 has been classified as Green List (High Evidence).
Mendeliome v1.4446 RSF1 Rylee Peters Marked gene: RSF1 as ready
Mendeliome v1.4446 RSF1 Rylee Peters Gene: rsf1 has been classified as Green List (High Evidence).
Mendeliome v1.4446 PMP22 Sangavi Sivagnanasundram reviewed gene: PMP22: Rating: GREEN; Mode of pathogenicity: None; Publications: 32412171, 31777123, 32719652; Phenotypes: Charcot-Marie-Tooth disease type 3 MONDO:0007790, Charcot-Marie-Tooth disease type 1A MONDO:0007309, hereditary neuropathy with liability to pressure palsies MONDO:0008087; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.536 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to 30976112
Fetal anomalies v1.535 LRRC32 Zornitza Stark reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: 41041957; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay - MIM#619074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.312 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to PMID: 30976112
Clefting disorders v0.311 LRRC32 Zornitza Stark reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: 41041957; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Syndromic Retinopathy v0.246 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to 30976112
Syndromic Retinopathy v0.245 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Added comment: Further family reported in PMID 41041957 with homozygous missense.; Changed publications: 30976112, 41041957
Intellectual disability syndromic and non-syndromic v1.675 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to 30976112
Intellectual disability syndromic and non-syndromic v1.674 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Added comment: Further family reported in PMID 41041957, homozygous missense variant.; Changed publications: 30976112, 41041957
Mendeliome v1.4446 LRRC32 Zornitza Stark Publications for gene: LRRC32 were set to 30976112
Mendeliome v1.4445 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Added comment: Further family reported in PMID 41041957, homozygous missense variant.; Changed publications: 30976112, 41041957
Neurodegenerative disease - adult onset v6.182 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Ataxia; Hereditary Spastic Paraplegia; Early-onset Dementia; Motor Neurone Disease
Cataract v0.629 MIR204 Zornitza Stark Marked gene: MIR204 as ready
Cataract v0.629 MIR204 Zornitza Stark Gene: mir204 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.56 MIR204 Zornitza Stark Marked gene: MIR204 as ready
Anophthalmia_Microphthalmia_Coloboma v1.56 MIR204 Zornitza Stark Gene: mir204 has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.239 Zornitza Stark Copied gene MIR204 from panel Mendeliome
Retinitis pigmentosa v0.239 MIR204 Zornitza Stark gene: MIR204 was added
gene: MIR204 was added to Retinitis pigmentosa. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: MIR204.
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975; 38867642; 20713703; 31332443
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Cataract v0.629 Zornitza Stark Copied gene MIR204 from panel Mendeliome
Cataract v0.629 MIR204 Zornitza Stark gene: MIR204 was added
gene: MIR204 was added to Cataract. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: MIR204.
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975; 38867642; 20713703; 31332443
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Cone-rod Dystrophy v0.59 MIR204 Zornitza Stark Classified gene: MIR204 as Red List (low evidence)
Cone-rod Dystrophy v0.59 MIR204 Zornitza Stark Gene: mir204 has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.58 MIR204 Zornitza Stark reviewed gene: MIR204: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Anophthalmia_Microphthalmia_Coloboma v1.56 Zornitza Stark Copied gene MIR204 from panel Mendeliome
Anophthalmia_Microphthalmia_Coloboma v1.56 MIR204 Zornitza Stark gene: MIR204 was added
gene: MIR204 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert Review Green,Literature
non-coding gene tags were added to gene: MIR204.
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975; 38867642; 20713703; 31332443
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Optic Atrophy v1.68 MIR204 Zornitza Stark Classified gene: MIR204 as Red List (low evidence)
Optic Atrophy v1.68 MIR204 Zornitza Stark Gene: mir204 has been classified as Red List (Low Evidence).
Optic Atrophy v1.67 MIR204 Zornitza Stark reviewed gene: MIR204: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.4445 MIR204 Zornitza Stark Publications for gene: MIR204 were set to 26056285; 37321975
Mendeliome v1.4444 MIR204 Zornitza Stark Classified gene: MIR204 as Green List (high evidence)
Mendeliome v1.4444 MIR204 Zornitza Stark Gene: mir204 has been classified as Green List (High Evidence).
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.

MODERATE by ClinGen.
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development.

Mouse model in PMID 31332443 recapitulates retinal phenotype.
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed publications: 38867642, 20713703, 31332443
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed publications: 38867642, 20713703
Mendeliome v1.4443 MIR204 Zornitza Stark changed review comment from: Two families only; to: Third family reported in PMID 38867642: variant n.37C>T segregated with disease in 4 individuals from the same family, all with coloboma, at least two with RP as well.

PMID 20713703: medaka fish model recapitulates coloboma and impaired lens development
Mendeliome v1.4443 MIR204 Zornitza Stark edited their review of gene: MIR204: Changed rating: GREEN; Changed publications: 38867642; Changed phenotypes: Retinal dystrophy and iris coloboma with or without cataract (MIM#616722); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4443 MIR204 Zornitza Stark reviewed gene: MIR204: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.674 Rylee Peters Copied gene RSF1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.674 RSF1 Rylee Peters gene: RSF1 was added
gene: RSF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RSF1 were set to 41606215
Phenotypes for gene: RSF1 were set to Neurodevelopmental disorder, MONDO:0700092, RSF1-related
Mendeliome v1.4443 RSF1 Rylee Peters Classified gene: RSF1 as Green List (high evidence)
Mendeliome v1.4443 RSF1 Rylee Peters Gene: rsf1 has been classified as Green List (High Evidence).
Mendeliome v1.4442 RSF1 Rylee Peters gene: RSF1 was added
gene: RSF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RSF1 were set to 41606215
Phenotypes for gene: RSF1 were set to Neurodevelopmental disorder, MONDO:0700092, RSF1-related
Review for gene: RSF1 was set to GREEN
Added comment: PMID: 41606215 describes 11 individuals from 11 unrelated families with heterozygous RSF1 variants causing a syndromic neurodevelopmental disorder with intellectual disability or limit scores (7/11), ASD (4/11) and developmental delay (6/11). Other features described include dysmorphism (5/7), variable macro‑/microcephaly (3/6), epilepsy (2/7), and brain MRI anomalies (2/4). Majority of the variants are de novo, one was inherited from a mosaic mother and another inherited from an affected father.
Sources: Literature
Fetal anomalies v1.535 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Fetal anomalies v1.535 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Fetal anomalies v1.535 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Fetal anomalies v1.534 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Fetal anomalies v1.534 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Fetal anomalies v1.533 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Growth failure v1.99 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Growth failure v1.98 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Skeletal dysplasia v0.416 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Skeletal dysplasia v0.415 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Microcephaly v1.413 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Microcephaly v1.412 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Mendeliome v1.4441 GINS3 Zornitza Stark Phenotypes for gene: GINS3 were changed from Meier-Gorlin syndrome, MONDO:0016817, GINS3-related to Meier-Gorlin syndrome 9, MIM# 621512
Mendeliome v1.4440 GINS3 Zornitza Stark edited their review of gene: GINS3: Changed phenotypes: Meier-Gorlin syndrome 9, MIM# 621512
Mendeliome v1.4440 CFAP70 Bryony Thompson gene: CFAP70 was added
gene: CFAP70 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP70 were set to 31621862
Phenotypes for gene: CFAP70 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP70 was set to RED
Added comment: A single case reported.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.113 Bryony Thompson Copied gene QRICH2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.113 QRICH2 Bryony Thompson gene: QRICH2 was added
gene: QRICH2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: QRICH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QRICH2 were set to 30683861; 31292949
Phenotypes for gene: QRICH2 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4439 QRICH2 Bryony Thompson Classified gene: QRICH2 as Green List (high evidence)
Mendeliome v1.4439 QRICH2 Bryony Thompson Gene: qrich2 has been classified as Green List (High Evidence).
Mendeliome v1.4438 QRICH2 Bryony Thompson gene: QRICH2 was added
gene: QRICH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: QRICH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QRICH2 were set to 30683861; 31292949
Phenotypes for gene: QRICH2 were set to spermatogenic failure MONDO:0004983
Review for gene: QRICH2 was set to GREEN
Added comment: At least 4 unrelated men and a supporting mouse model.
Sources: Literature
Deafness_IsolatedAndComplex v1.331 Bryony Thompson Copied gene TMTC4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.331 TMTC4 Bryony Thompson gene: TMTC4 was added
gene: TMTC4 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: TMTC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMTC4 were set to 37943620
Phenotypes for gene: TMTC4 were set to hearing loss, autosomal recessive MONDO:0019588
Mendeliome v1.4437 TMTC4 Bryony Thompson gene: TMTC4 was added
gene: TMTC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMTC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMTC4 were set to 37943620
Phenotypes for gene: TMTC4 were set to hearing loss, autosomal recessive MONDO:0019588
Review for gene: TMTC4 was set to RED
Added comment: A single family reported and a supporting mouse model
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.112 Bryony Thompson Copied gene WDR66 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.112 WDR66 Bryony Thompson gene: WDR66 was added
gene: WDR66 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
new gene name tags were added to gene: WDR66.
Mode of inheritance for gene: WDR66 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR66 were set to 30122540; 30122541
Phenotypes for gene: WDR66 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4436 WDR66 Bryony Thompson Classified gene: WDR66 as Green List (high evidence)
Mendeliome v1.4436 WDR66 Bryony Thompson Gene: wdr66 has been classified as Green List (High Evidence).
Mendeliome v1.4435 WDR66 Bryony Thompson gene: WDR66 was added
gene: WDR66 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: WDR66.
Mode of inheritance for gene: WDR66 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR66 were set to 30122540; 30122541
Phenotypes for gene: WDR66 were set to spermatogenic failure MONDO:0004983
Review for gene: WDR66 was set to GREEN
Added comment: At least 10 families/men reported.
Sources: Literature
Corneal Dystrophy v1.21 Bryony Thompson Copied gene TUBA3D from panel Mendeliome
Corneal Dystrophy v1.21 TUBA3D Bryony Thompson gene: TUBA3D was added
gene: TUBA3D was added to Corneal Dystrophy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TUBA3D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA3D were set to 29051577
Phenotypes for gene: TUBA3D were set to keratoconus MONDO:0015486
Mendeliome v1.4434 TUBA3D Bryony Thompson Classified gene: TUBA3D as Amber List (moderate evidence)
Mendeliome v1.4434 TUBA3D Bryony Thompson Gene: tuba3d has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4433 TUBA3D Bryony Thompson gene: TUBA3D was added
gene: TUBA3D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBA3D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA3D were set to 29051577
Phenotypes for gene: TUBA3D were set to keratoconus MONDO:0015486
Review for gene: TUBA3D was set to AMBER
Added comment: 4 cases (including twins) with 2 variants. Functional analysis showed that the mutant proteins led to higher expression of matrix metalloproteinase genes and higher levels of oxidative stress, which the authors suggested would reduce extracellular matrix in the corneas and contribute to stromal thinning.
Sources: Literature
Pain syndromes v0.38 Bryony Thompson Copied gene ZFHX2 from panel Mendeliome
Pain syndromes v0.38 ZFHX2 Bryony Thompson gene: ZFHX2 was added
gene: ZFHX2 was added to Pain syndromes. Sources: Literature
Mode of inheritance for gene: ZFHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX2 were set to 29253101
Phenotypes for gene: ZFHX2 were set to congenital insensitivity to pain syndrome, Marsili type MONDO:0958106
Mendeliome v1.4432 ZFHX2 Bryony Thompson gene: ZFHX2 was added
gene: ZFHX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX2 were set to 29253101
Phenotypes for gene: ZFHX2 were set to congenital insensitivity to pain syndrome, Marsili type MONDO:0958106
Review for gene: ZFHX2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.111 Bryony Thompson Copied gene CFAP44 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.111 CFAP44 Bryony Thompson gene: CFAP44 was added
gene: CFAP44 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CFAP44 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP44 were set to 28552195; 29277146; 29449551
Phenotypes for gene: CFAP44 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4431 CFAP44 Bryony Thompson Classified gene: CFAP44 as Green List (high evidence)
Mendeliome v1.4431 CFAP44 Bryony Thompson Gene: cfap44 has been classified as Green List (High Evidence).
Mendeliome v1.4430 CFAP44 Bryony Thompson gene: CFAP44 was added
gene: CFAP44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP44 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP44 were set to 28552195; 29277146; 29449551
Phenotypes for gene: CFAP44 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP44 was set to GREEN
Added comment: At least 11 men reported with biallelic variants and a supporting mouse model.
Sources: Literature
Haem degradation and bilirubin metabolism defects v0.20 Bryony Thompson Copied gene CLPX from panel Mendeliome
Haem degradation and bilirubin metabolism defects v0.20 CLPX Bryony Thompson gene: CLPX was added
gene: CLPX was added to Haem degradation and bilirubin metabolism defects. Sources: Literature
Mode of inheritance for gene: CLPX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLPX were set to 28874591; 25957689
Phenotypes for gene: CLPX were set to protoporphyria, erythropoietic, 2 MONDO:0060729
Mendeliome v1.4429 CLPX Bryony Thompson gene: CLPX was added
gene: CLPX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLPX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLPX were set to 28874591; 25957689
Phenotypes for gene: CLPX were set to protoporphyria, erythropoietic, 2 MONDO:0060729
Review for gene: CLPX was set to RED
Added comment: A single family reported and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4428 AK7 Bryony Thompson reviewed gene: AK7: Rating: RED; Mode of pathogenicity: None; Publications: 29365104; Phenotypes: spermatogenic failure MONDO:0004983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.110 Bryony Thompson Copied gene AK9 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.110 AK9 Bryony Thompson gene: AK9 was added
gene: AK9 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: AK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK9 were set to 37713809
Phenotypes for gene: AK9 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4428 AK9 Bryony Thompson Classified gene: AK9 as Green List (high evidence)
Mendeliome v1.4428 AK9 Bryony Thompson Gene: ak9 has been classified as Green List (High Evidence).
Mendeliome v1.4427 AK9 Bryony Thompson gene: AK9 was added
gene: AK9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK9 were set to 37713809
Phenotypes for gene: AK9 were set to spermatogenic failure MONDO:0004983
Review for gene: AK9 was set to GREEN
Added comment: At least 5 unrelated men and a supporting mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.673 Bryony Thompson Copied gene EXOC8 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.673 EXOC8 Bryony Thompson gene: EXOC8 was added
gene: EXOC8 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: EXOC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC8 were set to 32103185; 22700954; 36344539; 35460391
Phenotypes for gene: EXOC8 were set to neurodevelopmental disorder with microcephaly, seizures, and brain atrophy MONDO:0033662
Mendeliome v1.4426 EXOC8 Bryony Thompson Classified gene: EXOC8 as Green List (high evidence)
Mendeliome v1.4426 EXOC8 Bryony Thompson Gene: exoc8 has been classified as Green List (High Evidence).
Mendeliome v1.4425 EXOC8 Bryony Thompson gene: EXOC8 was added
gene: EXOC8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC8 were set to 32103185; 22700954; 36344539; 35460391
Phenotypes for gene: EXOC8 were set to neurodevelopmental disorder with microcephaly, seizures, and brain atrophy MONDO:0033662
Review for gene: EXOC8 was set to GREEN
Added comment: At least 4 families/cases with a neurodevelopmental phenotype.
Sources: Literature
Mendeliome v1.4424 TUBB6 Bryony Thompson gene: TUBB6 was added
gene: TUBB6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBB6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB6 were set to 29016863
Phenotypes for gene: TUBB6 were set to facial palsy, congenital, with ptosis and velopharyngeal dysfunction MONDO:0060589
Review for gene: TUBB6 was set to RED
Added comment: A single family reported.
Sources: Literature
Mendeliome v1.4423 EPS8L3 Bryony Thompson gene: EPS8L3 was added
gene: EPS8L3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EPS8L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPS8L3 were set to 23099647
Phenotypes for gene: EPS8L3 were set to Marie Unna hereditary hypotrichosis MONDO:0018631
Review for gene: EPS8L3 was set to RED
Added comment: A single family reported.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v1.18 Bryony Thompson Copied gene MIR2861 from panel Mendeliome
Osteogenesis Imperfecta and Osteoporosis v1.18 MIR2861 Bryony Thompson gene: MIR2861 was added
gene: MIR2861 was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Literature
Mode of inheritance for gene: MIR2861 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MIR2861 were set to 19920351
Phenotypes for gene: MIR2861 were set to osteoporosis MONDO:0005298
Mendeliome v1.4422 MIR2861 Bryony Thompson gene: MIR2861 was added
gene: MIR2861 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MIR2861 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MIR2861 were set to 19920351
Phenotypes for gene: MIR2861 were set to osteoporosis MONDO:0005298
Review for gene: MIR2861 was set to RED
Added comment: A single family reported.
Sources: Literature
Proteinuria v0.235 Bryony Thompson Copied gene AVIL from panel Mendeliome
Proteinuria v0.235 AVIL Bryony Thompson gene: AVIL was added
gene: AVIL was added to Proteinuria. Sources: Expert Review Green,Literature
Mode of inheritance for gene: AVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AVIL were set to 29058690
Phenotypes for gene: AVIL were set to Nephrotic syndrome, type 21 MONDO:0032826
Mendeliome v1.4421 AVIL Bryony Thompson Classified gene: AVIL as Green List (high evidence)
Mendeliome v1.4421 AVIL Bryony Thompson Gene: avil has been classified as Green List (High Evidence).
Mendeliome v1.4420 AVIL Bryony Thompson gene: AVIL was added
gene: AVIL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AVIL were set to 29058690
Phenotypes for gene: AVIL were set to Nephrotic syndrome, type 21 MONDO:0032826
Review for gene: AVIL was set to GREEN
Added comment: 3 cases with 4 different variants and supporting in vitro functional assays demonstrating that the variants altered podocyte migration.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.109 Bryony Thompson Copied gene SPACA1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.109 SPACA1 Bryony Thompson gene: SPACA1 was added
gene: SPACA1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SPACA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPACA1 were set to 34172998; 22949614
Phenotypes for gene: SPACA1 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4419 SPACA1 Bryony Thompson gene: SPACA1 was added
gene: SPACA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPACA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPACA1 were set to 34172998; 22949614
Phenotypes for gene: SPACA1 were set to spermatogenic failure MONDO:0004983
Review for gene: SPACA1 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Mendeliome v1.4418 ABCA5 Bryony Thompson gene: ABCA5 was added
gene: ABCA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ABCA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA5 were set to 24831815
Phenotypes for gene: ABCA5 were set to gingival fibromatosis-hypertrichosis syndrome MONDO:0007610
Review for gene: ABCA5 was set to RED
Added comment: A single case was reported, and a supporting mouse model
Sources: Literature
Incidentalome v0.429 Bryony Thompson Copied gene RNF43 from panel Colorectal Cancer and Polyposis
Incidentalome v0.429 RNF43 Bryony Thompson gene: RNF43 was added
gene: RNF43 was added to Incidentalome. Sources: Expert Review Green,Literature,Expert Review,Expert list
Mode of inheritance for gene: RNF43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF43 were set to PMID: 24512911, 34541672, 27329244, 27081527, 29330307
Phenotypes for gene: RNF43 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Sessile serrated polyposis cancer syndrome, MONDO:0014919; Sessile serrated polyposis cancer syndrome, MIM#617108
Mendeliome v1.4417 TRIM44 Bryony Thompson Marked gene: TRIM44 as ready
Mendeliome v1.4417 TRIM44 Bryony Thompson Gene: trim44 has been classified as Red List (Low Evidence).
Mendeliome v1.4417 TRIM44 Bryony Thompson gene: TRIM44 was added
gene: TRIM44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM44 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM44 were set to 26394807
Phenotypes for gene: TRIM44 were set to Aniridia 3 MONDO:0014938
Review for gene: TRIM44 was set to RED
Added comment: A single family reported
Sources: Literature
Ichthyosis and Porokeratosis v1.24 Bryony Thompson Copied gene SLC17A9 from panel Mendeliome
Ichthyosis and Porokeratosis v1.24 SLC17A9 Bryony Thompson gene: SLC17A9 was added
gene: SLC17A9 was added to Ichthyosis and Porokeratosis. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SLC17A9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC17A9 were set to 25180256; 25596766
Phenotypes for gene: SLC17A9 were set to disseminated superficial actinic porokeratosis MONDO:0019212
Mendeliome v1.4416 SLC17A9 Bryony Thompson Marked gene: SLC17A9 as ready
Mendeliome v1.4416 SLC17A9 Bryony Thompson Gene: slc17a9 has been classified as Green List (High Evidence).
Mendeliome v1.4416 SLC17A9 Bryony Thompson Classified gene: SLC17A9 as Green List (high evidence)
Mendeliome v1.4416 SLC17A9 Bryony Thompson Gene: slc17a9 has been classified as Green List (High Evidence).
Mendeliome v1.4415 SLC17A9 Bryony Thompson gene: SLC17A9 was added
gene: SLC17A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC17A9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC17A9 were set to 25180256; 25596766
Phenotypes for gene: SLC17A9 were set to disseminated superficial actinic porokeratosis MONDO:0019212
Review for gene: SLC17A9 was set to GREEN
Added comment: 3 families reported with evidence of segregation with disease.
Sources: Literature
Mendeliome v1.4414 CENPT Bryony Thompson Marked gene: CENPT as ready
Mendeliome v1.4414 CENPT Bryony Thompson Gene: cenpt has been classified as Red List (Low Evidence).
Mendeliome v1.4414 CENPT Bryony Thompson gene: CENPT was added
gene: CENPT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to short stature and microcephaly with genital anomalies MONDO:0032875
Review for gene: CENPT was set to RED
Added comment: A single family reported, and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4413 BMS1 Bryony Thompson Marked gene: BMS1 as ready
Mendeliome v1.4413 BMS1 Bryony Thompson Gene: bms1 has been classified as Red List (Low Evidence).
Mendeliome v1.4413 BMS1 Bryony Thompson gene: BMS1 was added
gene: BMS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMS1 were set to 23785305
Phenotypes for gene: BMS1 were set to aplasia cutis congenita MONDO:0007145
Review for gene: BMS1 was set to RED
Added comment: A single family reported.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.108 Bryony Thompson Copied gene TTC21A from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.108 TTC21A Bryony Thompson gene: TTC21A was added
gene: TTC21A was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TTC21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21A were set to 30929735
Phenotypes for gene: TTC21A were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4412 TTC21A Bryony Thompson Marked gene: TTC21A as ready
Mendeliome v1.4412 TTC21A Bryony Thompson Gene: ttc21a has been classified as Green List (High Evidence).
Mendeliome v1.4412 TTC21A Bryony Thompson Classified gene: TTC21A as Green List (high evidence)
Mendeliome v1.4412 TTC21A Bryony Thompson Gene: ttc21a has been classified as Green List (High Evidence).
Mendeliome v1.4411 TTC21A Bryony Thompson gene: TTC21A was added
gene: TTC21A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC21A were set to 30929735
Phenotypes for gene: TTC21A were set to spermatogenic failure MONDO:0004983
Review for gene: TTC21A was set to GREEN
Added comment: At least 3 men reported with biallelic variants and a supporting mouse model
Sources: Literature
Mendeliome v1.4410 Bryony Thompson Copied gene DNAL4 from panel Mirror movements
Mendeliome v1.4410 DNAL4 Bryony Thompson gene: DNAL4 was added
gene: DNAL4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DNAL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAL4 were set to 25098561; 25236653
Phenotypes for gene: DNAL4 were set to Mirror movements 3 MIM#616059
Monogenic Diabetes v0.204 Bryony Thompson Copied gene MAFA from panel Mendeliome
Monogenic Diabetes v0.204 MAFA Bryony Thompson gene: MAFA was added
gene: MAFA was added to Monogenic Diabetes. Sources: Expert Review Green,Other
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFA were set to 29339498
Phenotypes for gene: MAFA were set to Insulinomatosis and diabetes mellitus, OMIM #:147630
Cardiomyopathy_Paediatric v0.222 DSG2 Zornitza Stark Marked gene: DSG2 as ready
Cardiomyopathy_Paediatric v0.222 DSG2 Zornitza Stark Gene: dsg2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.222 DSG2 Zornitza Stark Publications for gene: DSG2 were set to
Cardiomyopathy_Paediatric v0.221 DSG2 Zornitza Stark Mode of inheritance for gene: DSG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.220 Zornitza Stark Added reviews for gene DSG2 from panel Arrhythmogenic Cardiomyopathy
Infertility and Recurrent Pregnancy Loss v1.107 Bryony Thompson Copied gene MAATS1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.107 MAATS1 Bryony Thompson gene: MAATS1 was added
gene: MAATS1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
new gene name tags were added to gene: MAATS1.
Mode of inheritance for gene: MAATS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAATS1 were set to 32161152
Phenotypes for gene: MAATS1 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4409 MAATS1 Bryony Thompson Classified gene: MAATS1 as Green List (high evidence)
Mendeliome v1.4409 MAATS1 Bryony Thompson Gene: maats1 has been classified as Green List (High Evidence).
Mendeliome v1.4408 MAATS1 Bryony Thompson gene: MAATS1 was added
gene: MAATS1 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: MAATS1.
Mode of inheritance for gene: MAATS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAATS1 were set to 32161152
Phenotypes for gene: MAATS1 were set to spermatogenic failure MONDO:0004983
Review for gene: MAATS1 was set to GREEN
Added comment: 6 unrelated men of North African origin homozygous for 2 different variants and a supporting Trypanosoma brucei model.
Sources: Literature
Monogenic Diabetes v0.203 Bryony Thompson Copied gene CELA2A from panel Mendeliome
Monogenic Diabetes v0.203 CELA2A Bryony Thompson gene: CELA2A was added
gene: CELA2A was added to Monogenic Diabetes. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CELA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELA2A were set to 31358993
Phenotypes for gene: CELA2A were set to abdominal obesity-metabolic syndrome 4 MONDO:0032837
Dyslipidaemia v0.48 Bryony Thompson Copied gene CELA2A from panel Mendeliome
Dyslipidaemia v0.48 CELA2A Bryony Thompson gene: CELA2A was added
gene: CELA2A was added to Dyslipidaemia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CELA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELA2A were set to 31358993
Phenotypes for gene: CELA2A were set to abdominal obesity-metabolic syndrome 4 MONDO:0032837
Mendeliome v1.4407 CELA2A Bryony Thompson Classified gene: CELA2A as Green List (high evidence)
Mendeliome v1.4407 CELA2A Bryony Thompson Gene: cela2a has been classified as Green List (High Evidence).
Mendeliome v1.4406 CELA2A Bryony Thompson gene: CELA2A was added
gene: CELA2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELA2A were set to 31358993
Phenotypes for gene: CELA2A were set to abdominal obesity-metabolic syndrome 4 MONDO:0032837
Review for gene: CELA2A was set to GREEN
Added comment: 4 families/cases with a combination of the following features obesity, coronary artery disease, hypertriglyceridemia, hypertension, and type 2 diabetes. Segregation evidence in a large family and supporting in vitro fucntional studies.
Sources: Literature
Mendeliome v1.4405 TRIM36 Bryony Thompson gene: TRIM36 was added
gene: TRIM36 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM36 were set to 28087737
Phenotypes for gene: TRIM36 were set to anencephaly MONDO:0000819
Review for gene: TRIM36 was set to RED
Added comment: A single foetus was reported with a homozygous variant.
Sources: Literature
Oligodontia v0.33 Bryony Thompson Copied gene GREM2 from panel Mendeliome
Oligodontia v0.33 GREM2 Bryony Thompson gene: GREM2 was added
gene: GREM2 was added to Oligodontia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GREM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREM2 were set to 26416033; 28992378; 24686385
Phenotypes for gene: GREM2 were set to Tooth agenesis, selective, 9 MONDO:0014999
Mendeliome v1.4404 GREM2 Bryony Thompson Classified gene: GREM2 as Amber List (moderate evidence)
Mendeliome v1.4404 GREM2 Bryony Thompson Gene: grem2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4403 GREM2 Bryony Thompson gene: GREM2 was added
gene: GREM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GREM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREM2 were set to 26416033; 28992378; 24686385
Phenotypes for gene: GREM2 were set to Tooth agenesis, selective, 9 MONDO:0014999
Review for gene: GREM2 was set to AMBER
Added comment: 3 missense variants reported in 8 cases. Incomplete penetrance and variable expressivity were demonstrated. Also, a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.106 Bryony Thompson Copied gene ZPBP from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.106 ZPBP Bryony Thompson gene: ZPBP was added
gene: ZPBP was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ZPBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPBP were set to 31985809; 17664285
Phenotypes for gene: ZPBP were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4402 ZPBP Bryony Thompson gene: ZPBP was added
gene: ZPBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZPBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPBP were set to 31985809; 17664285
Phenotypes for gene: ZPBP were set to spermatogenic failure MONDO:0004983
Review for gene: ZPBP was set to RED
Added comment: A single male case reported with a homozygous variant, and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.105 Bryony Thompson Copied gene NANOS1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.105 NANOS1 Bryony Thompson gene: NANOS1 was added
gene: NANOS1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NANOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NANOS1 were set to 23315541
Phenotypes for gene: NANOS1 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4401 NANOS1 Bryony Thompson Classified gene: NANOS1 as Amber List (moderate evidence)
Mendeliome v1.4401 NANOS1 Bryony Thompson Gene: nanos1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4400 NANOS1 Bryony Thompson gene: NANOS1 was added
gene: NANOS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NANOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NANOS1 were set to 23315541
Phenotypes for gene: NANOS1 were set to spermatogenic failure MONDO:0004983
Review for gene: NANOS1 was set to AMBER
Added comment: 5 men with 3 different non-synonymous variants and incomplete segregation. 2 of the variants are inframe deletions in repeat regions.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.672 Bryony Thompson Copied gene ARHGEF2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.672 ARHGEF2 Bryony Thompson gene: ARHGEF2 was added
gene: ARHGEF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ARHGEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF2 were set to 28453519
Phenotypes for gene: ARHGEF2 were set to neurodevelopmental disorder with midbrain and hindbrain malformations MONDO:0056797
Mendeliome v1.4399 ARHGEF2 Bryony Thompson gene: ARHGEF2 was added
gene: ARHGEF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF2 were set to 28453519
Phenotypes for gene: ARHGEF2 were set to neurodevelopmental disorder with midbrain and hindbrain malformations MONDO:0056797
Review for gene: ARHGEF2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.104 Bryony Thompson Copied gene TSGA10 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.104 TSGA10 Bryony Thompson gene: TSGA10 was added
gene: TSGA10 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TSGA10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSGA10 were set to 28905369
Phenotypes for gene: TSGA10 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4398 TSGA10 Bryony Thompson gene: TSGA10 was added
gene: TSGA10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSGA10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSGA10 were set to 28905369
Phenotypes for gene: TSGA10 were set to spermatogenic failure MONDO:0004983
Review for gene: TSGA10 was set to RED
Added comment: A single case reported with a homozygous variant.
Sources: Literature
Eye Anterior Segment Abnormalities v1.20 Bryony Thompson Copied gene ELP4 from panel Mendeliome
Eye Anterior Segment Abnormalities v1.20 ELP4 Bryony Thompson gene: ELP4 was added
gene: ELP4 was added to Eye Anterior Segment Abnormalities. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELP4 were set to 24290376; 17679951; 22991255; 26010655
Phenotypes for gene: ELP4 were set to ocular dysgenesis caused by defects in PAX6 regulation MONDO:0700246
Mode of pathogenicity for gene: ELP4 was set to Other
Cataract v0.628 Bryony Thompson Copied gene ELP4 from panel Mendeliome
Cataract v0.628 ELP4 Bryony Thompson gene: ELP4 was added
gene: ELP4 was added to Cataract. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELP4 were set to 24290376; 17679951; 22991255; 26010655
Phenotypes for gene: ELP4 were set to ocular dysgenesis caused by defects in PAX6 regulation MONDO:0700246
Mode of pathogenicity for gene: ELP4 was set to Other
Mendeliome v1.4397 ELP4 Bryony Thompson Marked gene: ELP4 as ready
Mendeliome v1.4397 ELP4 Bryony Thompson Gene: elp4 has been classified as Green List (High Evidence).
Mendeliome v1.4397 ELP4 Bryony Thompson Classified gene: ELP4 as Green List (high evidence)
Mendeliome v1.4397 ELP4 Bryony Thompson Gene: elp4 has been classified as Green List (High Evidence).
Mendeliome v1.4396 ELP4 Bryony Thompson gene: ELP4 was added
gene: ELP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ELP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELP4 were set to 24290376; 17679951; 22991255; 26010655
Phenotypes for gene: ELP4 were set to ocular dysgenesis caused by defects in PAX6 regulation MONDO:0700246
Mode of pathogenicity for gene: ELP4 was set to Other
Review for gene: ELP4 was set to GREEN
Added comment: At least 5 families/cases reported with ocular dysgenesis. The mechanism of disease appears to be monoallelic disruption of enhancer elements located in the introns of ELP4 but required for efficient PAX6 transactivation during ocular development through a feed-forward mechanism mediated by binding of the PAX6 transcription factor
Sources: Literature
Incidentalome v0.428 Bryony Thompson Copied gene VEZF1 from panel Dilated Cardiomyopathy
Incidentalome v0.428 VEZF1 Bryony Thompson gene: VEZF1 was added
gene: VEZF1 was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: VEZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VEZF1 were set to 36657711
Phenotypes for gene: VEZF1 were set to dilated cardiomyopathy MONDO:0005021
Dilated Cardiomyopathy v1.57 VEZF1 Bryony Thompson gene: VEZF1 was added
gene: VEZF1 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: VEZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VEZF1 were set to 36657711
Phenotypes for gene: VEZF1 were set to dilated cardiomyopathy MONDO:0005021
Review for gene: VEZF1 was set to RED
Added comment: A single family reported.
Sources: Literature
Atrial Fibrillation v1.7 Bryony Thompson Copied gene NUP155 from panel Mendeliome
Atrial Fibrillation v1.7 NUP155 Bryony Thompson gene: NUP155 was added
gene: NUP155 was added to Atrial Fibrillation. Sources: Literature
Mode of inheritance for gene: NUP155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP155 were set to 19070573
Phenotypes for gene: NUP155 were set to familial atrial fibrillation MONDO:0018054
Mendeliome v1.4395 NUP155 Bryony Thompson gene: NUP155 was added
gene: NUP155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP155 were set to 19070573
Phenotypes for gene: NUP155 were set to familial atrial fibrillation MONDO:0018054
Review for gene: NUP155 was set to RED
Added comment: A single family reported and a supporting mouse model
Sources: Literature
Mendeliome v1.4394 HDAC9 Bryony Thompson gene: HDAC9 was added
gene: HDAC9 was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: HDAC9.
Mode of inheritance for gene: HDAC9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC9 were set to 34750192; 35710300; 38318288
Phenotypes for gene: HDAC9 were set to Auriculocondylar syndrome MONDO:0000107
Review for gene: HDAC9 was set to RED
Added comment: Disputed classification by Craniofacial Malformations GCEP 20/11/2025
https://search.clinicalgenome.org/CCID:009067
Sources: ClinGen
Deafness_IsolatedAndComplex v1.330 Bryony Thompson Copied gene SLC44A4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.330 SLC44A4 Bryony Thompson gene: SLC44A4 was added
gene: SLC44A4 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: SLC44A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC44A4 were set to 28013291
Phenotypes for gene: SLC44A4 were set to nonsyndromic genetic hearing loss MONDO:0019497
Mendeliome v1.4393 SLC44A4 Bryony Thompson gene: SLC44A4 was added
gene: SLC44A4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC44A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC44A4 were set to 28013291
Phenotypes for gene: SLC44A4 were set to nonsyndromic genetic hearing loss MONDO:0019497
Review for gene: SLC44A4 was set to RED
Added comment: A single family reported and a supporting zebrafish model.
Sources: Literature
Mendeliome v1.4392 ADGRE2 Bryony Thompson gene: ADGRE2 was added
gene: ADGRE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRE2 were set to 26841242
Phenotypes for gene: ADGRE2 were set to autosomal dominant vibratory urticaria MONDO:0007447
Mode of pathogenicity for gene: ADGRE2 was set to Other
Review for gene: ADGRE2 was set to RED
Added comment: A single family reported segregating a gain-of-function missense variant.
Sources: Literature
Incidentalome v0.427 Bryony Thompson Copied gene PBRM1 from panel Kidney Cancer
Incidentalome v0.427 PBRM1 Bryony Thompson gene: PBRM1 was added
gene: PBRM1 was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: PBRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PBRM1 were set to 25911086
Phenotypes for gene: PBRM1 were set to renal cell carcinoma MONDO:0005086
Kidney Cancer v1.12 PBRM1 Bryony Thompson gene: PBRM1 was added
gene: PBRM1 was added to Kidney Cancer. Sources: Literature
Mode of inheritance for gene: PBRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PBRM1 were set to 25911086
Phenotypes for gene: PBRM1 were set to renal cell carcinoma MONDO:0005086
Review for gene: PBRM1 was set to RED
Added comment: A single family reported.
Sources: Literature
Arrhythmogenic Cardiomyopathy v0.78 DSG2 Zornitza Stark Publications for gene: DSG2 were set to 33831308
Arrhythmogenic Cardiomyopathy v0.77 DSG2 Zornitza Stark Mode of inheritance for gene: DSG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4391 Bryony Thompson Added reviews for gene TEX15 from panel Mendeliome
Mendeliome v1.4390 TEX15 Bryony Thompson Marked gene: TEX15 as ready
Mendeliome v1.4390 TEX15 Bryony Thompson Gene: tex15 has been classified as Green List (High Evidence).
Mendeliome v1.4390 TEX15 Bryony Thompson Classified gene: TEX15 as Green List (high evidence)
Mendeliome v1.4390 TEX15 Bryony Thompson Gene: tex15 has been classified as Green List (High Evidence).
Mendeliome v1.4389 TEX15 Bryony Thompson gene: TEX15 was added
gene: TEX15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TEX15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEX15 were set to 26199321; 28355598; 28303806
Phenotypes for gene: TEX15 were set to spermatogenic failure MONDO:0004983
Review for gene: TEX15 was set to GREEN
Added comment: At least 3 families reported with infertile males and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.103 Bryony Thompson Copied gene SPINK2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.103 SPINK2 Bryony Thompson gene: SPINK2 was added
gene: SPINK2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SPINK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINK2 were set to 28554943
Phenotypes for gene: SPINK2 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4388 SPINK2 Bryony Thompson gene: SPINK2 was added
gene: SPINK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPINK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINK2 were set to 28554943
Phenotypes for gene: SPINK2 were set to spermatogenic failure MONDO:0004983
Review for gene: SPINK2 was set to RED
Added comment: A single family reported and a supporting null mouse model.
Sources: Literature
Growth failure v1.98 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from Neurodevelopmental disorder, MONDO:0700092 to Microcephaly 31, primary, autosomal recessive, MIM# 621507
Growth failure v1.97 CDK4 Zornitza Stark edited their review of gene: CDK4: Changed phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507
Intellectual disability syndromic and non-syndromic v1.671 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from Neurodevelopmental disorder, MONDO:0700092, CDK4-related to Microcephaly 31, primary, autosomal recessive, MIM# 621507
Intellectual disability syndromic and non-syndromic v1.670 CDK4 Zornitza Stark edited their review of gene: CDK4: Changed phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507
Microcephaly v1.412 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from Neurodevelopmental disorder, MONDO:0700092 to Microcephaly 31, primary, autosomal recessive, MIM# 621507
Microcephaly v1.411 CDK4 Zornitza Stark edited their review of gene: CDK4: Changed phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507
Mendeliome v1.4387 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from Neurodevelopmental disorder, MONDO:0700092; {Melanoma, cutaneous malignant, 3} MIM#609048 to Microcephaly 31, primary, autosomal recessive, MIM# 621507; {Melanoma, cutaneous malignant, 3} MIM#609048
Mendeliome v1.4386 CDK4 Zornitza Stark edited their review of gene: CDK4: Changed phenotypes: Microcephaly 31, primary, autosomal recessive, MIM# 621507
Infertility and Recurrent Pregnancy Loss v1.102 Bryony Thompson Copied gene AKAP3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.102 AKAP3 Bryony Thompson gene: AKAP3 was added
gene: AKAP3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: AKAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKAP3 were set to 35228300; 31969357
Phenotypes for gene: AKAP3 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4386 AKAP3 Bryony Thompson Classified gene: AKAP3 as Amber List (moderate evidence)
Mendeliome v1.4386 AKAP3 Bryony Thompson Gene: akap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4385 AKAP3 Bryony Thompson gene: AKAP3 was added
gene: AKAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AKAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKAP3 were set to 35228300; 31969357
Phenotypes for gene: AKAP3 were set to spermatogenic failure MONDO:0004983
Review for gene: AKAP3 was set to AMBER
Added comment: 2 unrelated males from consanguineous families with homozygous variants (frameshift, missense), and supporting mouse model.
Sources: Literature
Deafness_IsolatedAndComplex v1.329 Bryony Thompson Copied gene GAB1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.329 GAB1 Bryony Thompson gene: GAB1 was added
gene: GAB1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: GAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAB1 were set to 29408807
Phenotypes for gene: GAB1 were set to hearing loss, autosomal recessive MONDO:0019588
Mendeliome v1.4384 GAB1 Bryony Thompson gene: GAB1 was added
gene: GAB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAB1 were set to 29408807
Phenotypes for gene: GAB1 were set to hearing loss, autosomal recessive MONDO:0019588
Review for gene: GAB1 was set to RED
Added comment: A single family reported.
Sources: Literature
Incidentalome v0.426 Bryony Thompson Copied gene SLC25A11 from panel Paraganglioma_phaeochromocytoma
Incidentalome v0.426 SLC25A11 Bryony Thompson gene: SLC25A11 was added
gene: SLC25A11 was added to Incidentalome. Sources: Expert Review Red,Literature,Expert Review,Expert list
Mode of inheritance for gene: SLC25A11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC25A11 were set to PMID: 29431636
Phenotypes for gene: SLC25A11 were set to Paragangliomas 6, MONDO:0032767; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 6, MIM#618464
Mendeliome v1.4383 TIMELESS Bryony Thompson Marked gene: TIMELESS as ready
Mendeliome v1.4383 TIMELESS Bryony Thompson Gene: timeless has been classified as Red List (Low Evidence).
Mendeliome v1.4383 TIMELESS Bryony Thompson gene: TIMELESS was added
gene: TIMELESS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIMELESS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIMELESS were set to 31138685
Phenotypes for gene: TIMELESS were set to Advance sleep phase syndrome MONDO:0015609
Review for gene: TIMELESS was set to RED
Added comment: A single family reported, and a supporting mouse model
Sources: Literature
Mendeliome v1.4382 Bryony Thompson Copied gene RPL21 from panel Hair disorders
Mendeliome v1.4382 RPL21 Bryony Thompson gene: RPL21 was added
gene: RPL21 was added to Mendeliome. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: RPL21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL21 were set to 21412954
Phenotypes for gene: RPL21 were set to Hypotrichosis 12 MIM#615885
Hair disorders v0.83 RPL21 Bryony Thompson edited their review of gene: RPL21: Changed rating: RED
Mendeliome v1.4381 IGSF3 Bryony Thompson gene: IGSF3 was added
gene: IGSF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IGSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGSF3 were set to 24372406
Phenotypes for gene: IGSF3 were set to familial congenital nasolacrimal duct obstruction MONDO:0007871
Review for gene: IGSF3 was set to RED
Added comment: A single consanguineous family reported with a homozygous variant.
Sources: Literature
Mendeliome v1.4380 PER3 Bryony Thompson gene: PER3 was added
gene: PER3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PER3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PER3 were set to 26903630
Phenotypes for gene: PER3 were set to advanced sleep phase syndrome MONDO:0015609
Review for gene: PER3 was set to RED
Added comment: A haplotype (P415A and H417R) segregating in a single family and common in gnomAD (0.5%).
Sources: Literature
Deafness_IsolatedAndComplex v1.328 Bryony Thompson Copied gene PDE1C from panel Mendeliome
Deafness_IsolatedAndComplex v1.328 PDE1C Bryony Thompson gene: PDE1C was added
gene: PDE1C was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PDE1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE1C were set to 29860631
Phenotypes for gene: PDE1C were set to autosomal dominant nonsyndromic hearing loss MONDO:0019587
Mendeliome v1.4379 PDE1C Bryony Thompson gene: PDE1C was added
gene: PDE1C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDE1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE1C were set to 29860631
Phenotypes for gene: PDE1C were set to autosomal dominant nonsyndromic hearing loss MONDO:0019587
Review for gene: PDE1C was set to RED
Added comment: A single family reported.
Sources: Literature
Deafness_IsolatedAndComplex v1.327 Bryony Thompson Copied gene PI4KB from panel Mendeliome
Deafness_IsolatedAndComplex v1.327 PI4KB Bryony Thompson gene: PI4KB was added
gene: PI4KB was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PI4KB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PI4KB were set to 33358777
Phenotypes for gene: PI4KB were set to hearing loss, autosomal dominant 87 MONDO:0859525
Mendeliome v1.4378 PI4KB Bryony Thompson Classified gene: PI4KB as Green List (high evidence)
Mendeliome v1.4378 PI4KB Bryony Thompson Gene: pi4kb has been classified as Green List (High Evidence).
Mendeliome v1.4377 PI4KB Bryony Thompson gene: PI4KB was added
gene: PI4KB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PI4KB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PI4KB were set to 33358777
Phenotypes for gene: PI4KB were set to hearing loss, autosomal dominant 87 MONDO:0859525
Review for gene: PI4KB was set to GREEN
Added comment: A missense variant (p.Gln121Arg) segregating in a family and 3 other missense variants (p.Val434Gly, p.Glu667Lys, p.Met739Arg) were identified in 5 unrelated "sporadic" cases. All 4 missense variants were overexpressed in zebrafish embryos, resulting in impaired hearing function, and a null zebrafish model had inner ear abnormalities and audiosensory impairment. Missense showed to have dominant negative effects.
Sources: Literature
Mendeliome v1.4376 MARK3 Bryony Thompson Marked gene: MARK3 as ready
Mendeliome v1.4376 MARK3 Bryony Thompson Gene: mark3 has been classified as Red List (Low Evidence).
Mendeliome v1.4376 MARK3 Bryony Thompson gene: MARK3 was added
gene: MARK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MARK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARK3 were set to 29771303
Phenotypes for gene: MARK3 were set to visual impairment and progressive phthisis bulbi MONDO:0032655
Review for gene: MARK3 was set to RED
Added comment: A single consanguineous family with a homozygous variant and a supporting drosphila model.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.200 Bryony Thompson Copied gene NRIP1 from panel Mendeliome
Congenital anomalies of the kidney and urinary tract (CAKUT) v0.200 NRIP1 Bryony Thompson gene: NRIP1 was added
gene: NRIP1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT). Sources: Expert Review Amber,Literature
Mode of inheritance for gene: NRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRIP1 were set to 28381549; 34525250
Phenotypes for gene: NRIP1 were set to congenital anomalies of kidney and urinary tract 3 MONDO:0032646
Mendeliome v1.4375 NRIP1 Bryony Thompson Marked gene: NRIP1 as ready
Mendeliome v1.4375 NRIP1 Bryony Thompson Gene: nrip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4375 NRIP1 Bryony Thompson Classified gene: NRIP1 as Amber List (moderate evidence)
Mendeliome v1.4375 NRIP1 Bryony Thompson Gene: nrip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4374 NRIP1 Bryony Thompson gene: NRIP1 was added
gene: NRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRIP1 were set to 28381549; 34525250
Phenotypes for gene: NRIP1 were set to congenital anomalies of kidney and urinary tract 3 MONDO:0032646
Review for gene: NRIP1 was set to AMBER
Added comment: 2 families segregating 2 different truncating variants, with incomplete penetrance (1 unaffected carrier). Also, a supporting mouse model. Another case reported with a missense variant inherited from the unaffected mother.
Sources: Literature
Mendeliome v1.4373 Bryony Thompson Copied gene SALL2 from panel Anophthalmia_Microphthalmia_Coloboma
Mendeliome v1.4373 SALL2 Bryony Thompson gene: SALL2 was added
gene: SALL2 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: SALL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SALL2 were set to 24412933
Phenotypes for gene: SALL2 were set to Coloboma, ocular, autosomal recessive, MIM#16820
Infertility and Recurrent Pregnancy Loss v1.101 Bryony Thompson Copied gene BRDT from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.101 BRDT Bryony Thompson gene: BRDT was added
gene: BRDT was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: BRDT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRDT were set to 32469048; 28199965; 22922464
Phenotypes for gene: BRDT were set to Spermatogenic failure MONDO:0004983
Mendeliome v1.4372 BRDT Bryony Thompson Marked gene: BRDT as ready
Mendeliome v1.4372 BRDT Bryony Thompson Gene: brdt has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4372 BRDT Bryony Thompson Classified gene: BRDT as Amber List (moderate evidence)
Mendeliome v1.4372 BRDT Bryony Thompson Gene: brdt has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4371 BRDT Bryony Thompson gene: BRDT was added
gene: BRDT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BRDT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRDT were set to 32469048; 28199965; 22922464
Phenotypes for gene: BRDT were set to Spermatogenic failure MONDO:0004983
Review for gene: BRDT was set to AMBER
Added comment: 2 cases with 2 different homozygous missense (one with a suggestive gain-of-function mechanism - G928D). A null mouse model had meiotic arrest of spermatogenesis.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.57 Bryony Thompson Copied gene MAPKAPK3 from panel Mendeliome
Macular Dystrophy/Stargardt Disease v0.57 MAPKAPK3 Bryony Thompson gene: MAPKAPK3 was added
gene: MAPKAPK3 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: MAPKAPK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPKAPK3 were set to 26744326
Phenotypes for gene: MAPKAPK3 were set to patterned macular dystrophy 3 MONDO:0014920
Mendeliome v1.4370 MAPKAPK3 Bryony Thompson gene: MAPKAPK3 was added
gene: MAPKAPK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPKAPK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPKAPK3 were set to 26744326
Phenotypes for gene: MAPKAPK3 were set to patterned macular dystrophy 3 MONDO:0014920
Review for gene: MAPKAPK3 was set to RED
Added comment: A single family reported, and a supporting mouse model
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.100 Bryony Thompson Copied gene TAF4B from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.100 TAF4B Bryony Thompson gene: TAF4B was added
gene: TAF4B was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TAF4B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF4B were set to 24431330; 15774719
Phenotypes for gene: TAF4B were set to spermatogenic failure MONDO:0004983
Incidentalome v0.425 Bryony Thompson Copied gene HOXB13 from panel Prostate Cancer
Incidentalome v0.425 HOXB13 Bryony Thompson gene: HOXB13 was added
gene: HOXB13 was added to Incidentalome. Sources: Expert Review Green,Literature,Expert Review,Expert list
Mode of inheritance for gene: HOXB13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXB13 were set to PMID: 22236224, 30730552, 38766261
Phenotypes for gene: HOXB13 were set to Prostate cancer, MONDO:0008315; Prostate cancer, susceptibility to, MIM#610997
Mendeliome v1.4369 TAF4B Bryony Thompson gene: TAF4B was added
gene: TAF4B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAF4B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF4B were set to 24431330; 15774719
Phenotypes for gene: TAF4B were set to spermatogenic failure MONDO:0004983
Review for gene: TAF4B was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Cataract v0.627 Bryony Thompson Copied gene CRYBA2 from panel Mendeliome
Cataract v0.627 CRYBA2 Bryony Thompson gene: CRYBA2 was added
gene: CRYBA2 was added to Cataract. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CRYBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYBA2 were set to 23508780; 37438446; 21212184; 38909969; 34014271; 28450710
Phenotypes for gene: CRYBA2 were set to cataract MONDO:0005129
Mendeliome v1.4368 CRYBA2 Bryony Thompson Marked gene: CRYBA2 as ready
Mendeliome v1.4368 CRYBA2 Bryony Thompson Gene: cryba2 has been classified as Green List (High Evidence).
Mendeliome v1.4368 CRYBA2 Bryony Thompson Classified gene: CRYBA2 as Green List (high evidence)
Mendeliome v1.4368 CRYBA2 Bryony Thompson Gene: cryba2 has been classified as Green List (High Evidence).
Mendeliome v1.4367 CRYBA2 Bryony Thompson gene: CRYBA2 was added
gene: CRYBA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRYBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYBA2 were set to 23508780; 37438446; 21212184; 38909969; 34014271; 28450710
Phenotypes for gene: CRYBA2 were set to cataract MONDO:0005129
Review for gene: CRYBA2 was set to GREEN
Added comment: 5 reported families/cases with missense variants, 3 families segregating variants with incomplete penetrance. Also, a supporting mouse model
Sources: Literature
Mendeliome v1.4366 Bryony Thompson Copied gene MMP14 from panel Skeletal dysplasia
Mendeliome v1.4366 MMP14 Bryony Thompson gene: MMP14 was added
gene: MMP14 was added to Mendeliome. Sources: Expert Review Amber
Mode of inheritance for gene: MMP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP14 were set to 29741626; 22922033; 10520996
Phenotypes for gene: MMP14 were set to Winchester syndrome 277950
Skeletal dysplasia v0.415 MMP14 Bryony Thompson Marked gene: MMP14 as ready
Skeletal dysplasia v0.415 MMP14 Bryony Thompson Gene: mmp14 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.415 MMP14 Bryony Thompson Publications for gene: MMP14 were set to 22922033
Skeletal dysplasia v0.414 MMP14 Bryony Thompson Classified gene: MMP14 as Amber List (moderate evidence)
Skeletal dysplasia v0.414 MMP14 Bryony Thompson Gene: mmp14 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.413 MMP14 Bryony Thompson reviewed gene: MMP14: Rating: AMBER; Mode of pathogenicity: None; Publications: 29741626, 22922033, 10520996; Phenotypes: multicentric osteolysis-nodulosis-arthropathy spectrum MONDO:0018298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4365 P4HA2 Bryony Thompson Classified gene: P4HA2 as Green List (high evidence)
Mendeliome v1.4365 P4HA2 Bryony Thompson Gene: p4ha2 has been classified as Green List (High Evidence).
Mendeliome v1.4364 P4HA2 Bryony Thompson gene: P4HA2 was added
gene: P4HA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: P4HA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P4HA2 were set to 25741866
Phenotypes for gene: P4HA2 were set to myopia MONDO:0001384
Review for gene: P4HA2 was set to GREEN
Added comment: At least 6 families reported with nonsyndromic myopia.
Sources: Literature
Mendeliome v1.4363 ITPR2 Bryony Thompson Marked gene: ITPR2 as ready
Mendeliome v1.4363 ITPR2 Bryony Thompson Gene: itpr2 has been classified as Red List (Low Evidence).
Mendeliome v1.4363 ITPR2 Bryony Thompson gene: ITPR2 was added
gene: ITPR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPR2 were set to 25329695
Phenotypes for gene: ITPR2 were set to isolated anhidrosis with normal sweat glands MONDO:0007118
Review for gene: ITPR2 was set to RED
Added comment: A single family reported and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.99 Bryony Thompson Copied gene SSX1 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.99 SSX1 Bryony Thompson gene: SSX1 was added
gene: SSX1 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SSX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SSX1 were set to 36796361
Phenotypes for gene: SSX1 were set to spermatogenic failure, X-linked, 5 MONDO:085947
Mendeliome v1.4362 SSX1 Bryony Thompson Marked gene: SSX1 as ready
Mendeliome v1.4362 SSX1 Bryony Thompson Gene: ssx1 has been classified as Green List (High Evidence).
Mendeliome v1.4362 SSX1 Bryony Thompson Classified gene: SSX1 as Green List (high evidence)
Mendeliome v1.4362 SSX1 Bryony Thompson Gene: ssx1 has been classified as Green List (High Evidence).
Mendeliome v1.4361 SSX1 Bryony Thompson gene: SSX1 was added
gene: SSX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SSX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SSX1 were set to 36796361
Phenotypes for gene: SSX1 were set to spermatogenic failure, X-linked, 5 MONDO:085947
Review for gene: SSX1 was set to GREEN
Added comment: At least 6 unrelated men with hemizygous variants and a supporting mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.98 Bryony Thompson Copied gene CT55 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.98 CT55 Bryony Thompson gene: CT55 was added
gene: CT55 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CT55 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CT55 were set to 36481789
Phenotypes for gene: CT55 were set to Spermatogenic failure MONDO:0004983
Mendeliome v1.4360 CT55 Bryony Thompson gene: CT55 was added
gene: CT55 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CT55 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CT55 were set to 36481789
Phenotypes for gene: CT55 were set to Spermatogenic failure MONDO:0004983
Review for gene: CT55 was set to RED
Added comment: 2 Chinese brothers with infertility, hemizygous for a nonsense variant and supporting mouse model.
Sources: Literature
Deafness_IsolatedAndComplex v1.326 Bryony Thompson Copied gene GPRASP2 from panel Mendeliome
Deafness_IsolatedAndComplex v1.326 GPRASP2 Bryony Thompson gene: GPRASP2 was added
gene: GPRASP2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: GPRASP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPRASP2 were set to 28096187; 41688572
Phenotypes for gene: GPRASP2 were set to X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome MONDO:0044702
Mendeliome v1.4359 GPRASP2 Bryony Thompson Marked gene: GPRASP2 as ready
Mendeliome v1.4359 GPRASP2 Bryony Thompson Gene: gprasp2 has been classified as Red List (Low Evidence).
Mendeliome v1.4359 GPRASP2 Bryony Thompson gene: GPRASP2 was added
gene: GPRASP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPRASP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPRASP2 were set to 28096187; 41688572
Phenotypes for gene: GPRASP2 were set to X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome MONDO:0044702
Review for gene: GPRASP2 was set to RED
Added comment: A single family reported segregating a hemizygous delins with deafness and a supporting deficient mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.97 Bryony Thompson Copied gene ADGRG2 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.97 ADGRG2 Bryony Thompson gene: ADGRG2 was added
gene: ADGRG2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ADGRG2 was set to Other
Publications for gene: ADGRG2 were set to 15367682; 27476656
Phenotypes for gene: ADGRG2 were set to congenital bilateral absence of vas deferens MONDO:0018801
Mendeliome v1.4358 ADGRG2 Bryony Thompson Marked gene: ADGRG2 as ready
Mendeliome v1.4358 ADGRG2 Bryony Thompson Gene: adgrg2 has been classified as Green List (High Evidence).
Mendeliome v1.4358 ADGRG2 Bryony Thompson Classified gene: ADGRG2 as Green List (high evidence)
Mendeliome v1.4358 ADGRG2 Bryony Thompson Gene: adgrg2 has been classified as Green List (High Evidence).
Mendeliome v1.4357 ADGRG2 Bryony Thompson gene: ADGRG2 was added
gene: ADGRG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRG2 was set to Other
Publications for gene: ADGRG2 were set to 15367682; 27476656
Phenotypes for gene: ADGRG2 were set to congenital bilateral absence of vas deferens MONDO:0018801
Review for gene: ADGRG2 was set to GREEN
Added comment: At least 4 men reported with hemizygous LoF variants and CBAVD. Supporting mouse model. The gene appears to have no biological relevance in women.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark Gene: insl3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.96 Zornitza Stark Copied gene INSL3 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.96 INSL3 Zornitza Stark gene: INSL3 was added
gene: INSL3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: INSL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: INSL3 were set to 12601553; 12970298; 11095425; 41369823; 37208861; 33095795
Phenotypes for gene: INSL3 were set to Cryptorchidism, MIM# 219050; Infertility disorder MONDO:0005047, INSL3-related
Mendeliome v1.4356 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from Cryptorchidism, MIM# 219050 to Cryptorchidism, MIM# 219050; Infertility disorder MONDO:0005047, INSL3-related
Mendeliome v1.4355 INSL3 Zornitza Stark Publications for gene: INSL3 were set to 12601553; 12970298; 11095425
Mendeliome v1.4354 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4353 INSL3 Zornitza Stark Classified gene: INSL3 as Green List (high evidence)
Mendeliome v1.4353 INSL3 Zornitza Stark Gene: insl3 has been classified as Green List (High Evidence).
Mendeliome v1.4352 INSL3 Zornitza Stark changed review comment from: Note some of the reported variants have relatively high population frequencies in gnomad, unclear if this is monogenic.; to: Initial association reported for mono-allelic variants: Note some of the reported variants have relatively high population frequencies in gnomad, unclear if this is monogenic.
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 33095795 reports a single individual with a homozygous missense variant c.52G>A p.V18M. Mouse knock‑out studies showed disrupted female cycles and reduced litter size; Changed publications: 12601553, 12970298, 11095425, 41369823, 37208861, 33095795; Changed phenotypes: Cryptorchidism, MIM# 219050, Infertility disorder MONDO:0005047, INSL3-related
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 37208861 reports a single individual with a homozygous frameshift loss‑of‑function variant c.143dupG (p.Arg50Profs*16) presenting with bilateral cryptorchidism diagnosed at birth, early orchidopexy, severe male infertility (non‑obstructive azoospermia, Sertoli‑cell‑only phenotype) and additional features (hypertonia, severe hearing loss, red‑green visual impairment). Functional impact demonstrated by absent INSL3 immunostaining in Leydig cells and undetectable serum INSL3 levels. Additional phenotypic features unlikely explained by INSL3 variant.; Changed publications: 12601553, 12970298, 11095425, 41369823, 37208861
Mendeliome v1.4352 INSL3 Zornitza Stark edited their review of gene: INSL3: Added comment: PMID 41369823 reports two unrelated Chinese Han individuals with homozygous frameshift INSL3 variants presenting with bilateral cryptorchidism, testicular atrophy, azoospermia and elevated FSH/LH. Functional assays (Western blot, immunofluorescence, Co‑IP) showed truncated proteins and loss of RXFP2 interaction; structural modelling predicted abnormal protein conformation; Changed publications: 12601553, 12970298, 11095425, 41369823
Mendeliome v1.4352 IGSF10 Zornitza Stark Publications for gene: IGSF10 were set to 27137492; 31042289; 40700020
Mendeliome v1.4351 IGSF10 Zornitza Stark Mode of inheritance for gene: IGSF10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4350 IGSF10 Zornitza Stark edited their review of gene: IGSF10: Added comment: PMID 31200363: two individuals from unrelated families with bi-allelic variants and hypogonadotropic hypogonadism.
PMID 33208564: single individual with mono-allelic LoF variant and hypogonadotropic hypogonadism.

Still a mixture of MOIs reported, little supportive data, some of the variants postulated to be associated with dominant disease have high pop frequencies.; Changed publications: 27137492, 31042289, 40700020, 31200363, 33208564
Dystonia and Chorea v0.340 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Dystonia and Chorea v0.340 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.340 EPG5 Zornitza Stark Classified gene: EPG5 as Green List (high evidence)
Dystonia and Chorea v0.340 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.339 EPG5 Zornitza Stark gene: EPG5 was added
gene: EPG5 was added to Dystonia and Chorea. Sources: Literature
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to 41053928; 36410285; 40192014
Phenotypes for gene: EPG5 were set to Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Review for gene: EPG5 was set to GREEN
Added comment: Neurodevelopmental disorder with parkinsonism or other movement abnormalities (NEDPAM) is an autosomal recessive disorder characterized by mild to severe developmental delay or intellectual disability and movement abnormalities including spasticity, early onset-parkinsonism with dystonia, myoclonus, or a combination of these. Movement abnormalities may have onset from birth to adulthood in the sixth decade of life. Adolescent-onset dystonia and parkinsonism on the background of neurodevelopmental delay may be rapidly progressive, with cognitive decline. Patients may have additional features such as seizures and optic nerve atrophy. PMIDs 41053928, 36410285 and 40192014 report over 100 affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.670 EPG5 Zornitza Stark Publications for gene: EPG5 were set to 23222957; 26917586
Intellectual disability syndromic and non-syndromic v1.669 EPG5 Zornitza Stark edited their review of gene: EPG5: Added comment: Neurodevelopmental disorder with parkinsonism or other movement abnormalities (NEDPAM) is an autosomal recessive disorder characterized by mild to severe developmental delay or intellectual disability and movement abnormalities including spasticity, early onset-parkinsonism with dystonia, myoclonus, or a combination of these. Movement abnormalities may have onset from birth to adulthood in the sixth decade of life. Adolescent-onset dystonia and parkinsonism on the background of neurodevelopmental delay may be rapidly progressive, with cognitive decline. Patients may have additional features such as seizures and optic nerve atrophy. PMIDs 41053928, 36410285 and 40192014 report over 100 affected individuals.; Changed publications: 23222957, 26917586, 41053928, 36410285, 40192014; Changed phenotypes: Vici syndrome, MIM# 242840, Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Lysosomal Storage Disorder v1.29 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Lysosomal Storage Disorder v1.29 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.29 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Disorders of autophagy; Vici syndrome MONDO:0009452 to Disorders of autophagy; Vici syndrome MONDO:0009452; Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Lysosomal Storage Disorder v1.28 EPG5 Zornitza Stark Publications for gene: EPG5 were set to 33674710; 34130600; 29884839
Lysosomal Storage Disorder v1.27 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 41053928, 36410285, 40192014; Phenotypes: Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4350 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, MIM# 242840 to Vici syndrome, MIM# 242840; Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Mendeliome v1.4349 EPG5 Zornitza Stark Publications for gene: EPG5 were set to 23222957; 26917586
Mendeliome v1.4348 EPG5 Zornitza Stark edited their review of gene: EPG5: Added comment: Neurodevelopmental disorder with parkinsonism or other movement abnormalities (NEDPAM) is an autosomal recessive disorder characterized by mild to severe developmental delay or intellectual disability and movement abnormalities including spasticity, early onset-parkinsonism with dystonia, myoclonus, or a combination of these. Movement abnormalities may have onset from birth to adulthood in the sixth decade of life. Adolescent-onset dystonia and parkinsonism on the background of neurodevelopmental delay may be rapidly progressive, with cognitive decline. Patients may have additional features such as seizures and optic nerve atrophy.

PMIDs 41053928, 36410285 and 40192014 report over 100 affected individuals.; Changed publications: 23222957, 26917586, 41053928, 36410285, 40192014; Changed phenotypes: Vici syndrome, MIM# 242840, Neurodevelopmental disorder with parkinsonism or other movement abnormalities, MIM# 621506
Infertility and Recurrent Pregnancy Loss v1.95 HNRNPR Lucy Spencer Phenotypes for gene: HNRNPR were changed from Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM#620073; Spermatogenic failure (MONDO:0004983), HNRNPR-related to Spermatogenic failure (MONDO:0004983), HNRNPR-related
Infertility and Recurrent Pregnancy Loss v1.94 HNRNPR Lucy Spencer Publications for gene: HNRNPR were set to 26795593; 31079900; 41618099
Infertility and Recurrent Pregnancy Loss v1.93 HNRNPR Lucy Spencer Mode of inheritance for gene: HNRNPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.92 HNRNPR Lucy Spencer Classified gene: HNRNPR as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.92 HNRNPR Lucy Spencer Gene: hnrnpr has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.91 Lucy Spencer Copied gene HNRNPR from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.91 HNRNPR Lucy Spencer gene: HNRNPR was added
gene: HNRNPR was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: HNRNPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HNRNPR were set to 26795593; 31079900; 41618099
Phenotypes for gene: HNRNPR were set to Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM#620073; Spermatogenic failure (MONDO:0004983), HNRNPR-related
Mendeliome v1.4348 HNRNPR Lucy Spencer Mode of inheritance for gene: HNRNPR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4347 HNRNPR Lucy Spencer Publications for gene: HNRNPR were set to 26795593; 31079900
Mendeliome v1.4346 HNRNPR Lucy Spencer Phenotypes for gene: HNRNPR were changed from Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM# 620073 to Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM#620073; Spermatogenic failure (MONDO:0004983), HNRNPR-related
Mendeliome v1.4345 HNRNPR Lucy Spencer reviewed gene: HNRNPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 41618099; Phenotypes: Spermatogenic failure (MONDO:0004983), HNRNPR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.83 Sarah Milton Added reviews for gene SSR3 from panel Mendeliome
Mendeliome v1.4345 SSR3 Sarah Milton reviewed gene: SSR3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32332102; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, SSR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Neurological Conditions v21.437 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Brain Calcification; Genetic Epilepsy; Ataxia; Hereditary Neuropathy; Hereditary Spastic Paraplegia; Congenital Disorders of Glycosylation; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Miscellaneous Metabolic Disorders; Early-onset Dementia; Motor Neurone Disease; Rhabdomyolysis and Metabolic Myopathy; Lysosomal Storage Disorder; Mitochondrial disease; Fatty Acid Oxidation Defects; Cerebral vascular malformations; Neurotransmitter Defects; Brain Channelopathies; Glycogen Storage Diseases; Neurodegeneration with brain iron accumulation; Leukodystrophy; Dystonia and Chorea; Peroxisomal Disorders; Metal Metabolism Disorders; Pain syndromes
Neuromuscular Superpanel v4.368 Bryony Thompson Changed child panels to: Ataxia; 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
Arrhythmogenic Cardiomyopathy v0.76 DSG2 Leah Frajman changed review comment from: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families has been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).; to: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families have been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).
Intellectual disability syndromic and non-syndromic v1.669 NLGN3 Lucy Spencer Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Asperger syndrome susceptibility, X-linked 1} - MIM#300494; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Autism v0.246 NLGN3 Lucy Spencer Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Asperger syndrome susceptibility, X-linked 1} - MIM#300494; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Arrhythmogenic Cardiomyopathy v0.76 DSG2 Leah Frajman changed review comment from: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families has been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).; to: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families has been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).
Arrhythmogenic Cardiomyopathy v0.76 DSG2 Leah Frajman changed review comment from: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families has been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).; to: Very well reported homozygous founder variant (p.(Phe531Cys)) present in at least nine families with ARVC/D summary in Wei 2024 (PMID: 39253717). Chen 2018 reported 8 individuals homozygous for this variant, however 25% of their heterozygous relatives were were mildly affected (PMID: 30454721). Suggested that fully penetrant when homozygous, but reduced penetrance in the heterozygous state.

Two additional families has been reported with the p.(Phe531Cys) in a compound heterozygous state with a multi-exon deletion, and a homozygous splice variant (PMID:33917638).
Arrhythmogenic Cardiomyopathy v0.76 DSG2 Leah Frajman reviewed gene: DSG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39253717, 30454721, 33917638; Phenotypes: Arrhythmogenic right ventricular dysplasia 10 (MIM#610193); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4345 NLGN3 Lucy Spencer Phenotypes for gene: NLGN3 were changed from X-linked complex neurodevelopmental disorder MONDO:0100148; {Asperger syndrome susceptibility, X-linked 1} - MIM#300494; {Autism susceptibility, X-linked 1} - MIM#300425 to X-linked complex neurodevelopmental disorder MONDO:0100148; {Autism susceptibility, X-linked 1} - MIM#300425
Mendeliome v1.4344 CCDC141 Zornitza Stark Phenotypes for gene: CCDC141 were changed from Anosmic hypogonadotropic hypogonadism to congenital hypogonadotropic hypogonadism, MONDO:0015770, CCDC141-related
Mendeliome v1.4343 CCDC141 Zornitza Stark Mode of inheritance for gene: CCDC141 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.424 SCN5A Lucy Spencer Phenotypes for gene: SCN5A were changed from Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900; Cardiomyopathy, dilated, 1E, MIM# 601154 to Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900; Cardiomyopathy, dilated, 1E, MIM# 601154; SCN5A-related cardiac rhythm disorder MONDO:1010181
Cardiac conduction disease v1.6 SCN5A Lucy Spencer reviewed gene: SCN5A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: SCN5A-related cardiac rhythm disorder MONDO:1010181; Mode of inheritance: None
Severe early-onset obesity v1.28 ADCY3 Zornitza Stark Publications for gene: ADCY3 were set to 11055432; 29311636; 29311637
Severe early-onset obesity v1.27 ADCY3 Zornitza Stark Classified gene: ADCY3 as Green List (high evidence)
Severe early-onset obesity v1.27 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.26 ADCY3 Zornitza Stark edited their review of gene: ADCY3: Added comment: PMID 39519366: reports a single consanguineous Pakistani family with a 4‑year‑old girl who presented with early‑onset severe obesity, hyperphagia, insulin resistance (acanthosis nigricans), and mild hepatomegaly. Exome‑panel sequencing identified a novel homozygous nonsense variant c.2520C>G (p.Thr840X). In vitro assays in 3T3‑L1 cells demonstrated markedly reduced CRE/SRE‑luciferase activity, lower cAMP production, increased lipid accumulation, and diminished lipolysis for the mutant protein, while structural modelling showed loss of the intracellular G‑protein‑binding segment.; Changed rating: GREEN; Changed publications: 11055432, 29311636, 29311637, 39519366
Cardiac conduction disease v1.6 SCN5A Lucy Spencer Phenotypes for gene: SCN5A were changed from progressive familial heart block MONDO:0019490 to progressive familial heart block MONDO:0019490; SCN5A-related cardiac rhythm disorder MONDO:1010181
Mendeliome v1.4342 ADCY3 Zornitza Stark Publications for gene: ADCY3 were set to 11055432; 29311636; 29311637
Mendeliome v1.4341 ADCY3 Zornitza Stark Classified gene: ADCY3 as Green List (high evidence)
Mendeliome v1.4341 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Green List (High Evidence).
Mendeliome v1.4340 ADCY3 Zornitza Stark reviewed gene: ADCY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39519366; Phenotypes: {Obesity, susceptibility to, BMIQ19} MIM#617885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Glaucoma congenital v1.10 Sarah Milton Copied Region PITX2 upstream regulatory region from panel Mendeliome
Glaucoma congenital v1.10 PITX2 upstream regulatory region Sarah Milton Region: PITX2 upstream regulatory region was added
Region: PITX2 upstream regulatory region was added to Glaucoma congenital. Sources: Literature
SV/CNV tags were added to Region: PITX2 upstream regulatory region.
Mode of inheritance for Region: PITX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX2 upstream regulatory region were set to PMID: 20881290, 28911203, 14991915, 9480756
Phenotypes for Region: PITX2 upstream regulatory region were set to Axenfeld-Rieger syndrome, MONDO:0019187
Eye Anterior Segment Abnormalities v1.19 Sarah Milton Copied Region PITX2 upstream regulatory region from panel Mendeliome
Eye Anterior Segment Abnormalities v1.19 PITX2 upstream regulatory region Sarah Milton Region: PITX2 upstream regulatory region was added
Region: PITX2 upstream regulatory region was added to Eye Anterior Segment Abnormalities. Sources: Literature
SV/CNV tags were added to Region: PITX2 upstream regulatory region.
Mode of inheritance for Region: PITX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX2 upstream regulatory region were set to PMID: 20881290, 28911203, 14991915, 9480756
Phenotypes for Region: PITX2 upstream regulatory region were set to Axenfeld-Rieger syndrome, MONDO:0019187
Mendeliome v1.4340 PITX2 upstream regulatory region Sarah Milton Region: PITX2 upstream regulatory region was added
Region: PITX2 upstream regulatory region was added to Mendeliome. Sources: Literature
SV/CNV tags were added to Region: PITX2 upstream regulatory region.
Mode of inheritance for Region: PITX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: PITX2 upstream regulatory region were set to PMID: 20881290, 28911203, 14991915, 9480756
Phenotypes for Region: PITX2 upstream regulatory region were set to Axenfeld-Rieger syndrome, MONDO:0019187
Review for Region: PITX2 upstream regulatory region was set to GREEN
Added comment: PITX2 encodes a homeodomain containing transcription factor.

There have been over 5 affected individuals across a number of publications with deletions in an agenic region approx 150kb upstream of PITX2 presenting with an Axenfeld Rieger phenotype.
There have also been reports of individuals with balanced translocations transecting the region on 4p with a similar phenotype.

Functional studies have interrogated this region identifying 11 conserved elements that are thought to represent enhancers. Zebrafish studies were performed by Volkmann et al with varying sized deletions in the region showing an effect on PITX2 gene expression.
Protas et al used a zebrafish model modified by CRISPR/Cas9 to delete an orthologous region similar to that seen in an affected individual. This resulted in recapitulation of the phenotype.

Note coordinates may not be precise (smaller deletions have been reported to cause disease).
Sources: Literature
Fetal anomalies v1.533 FGD5 Krithika Murali Phenotypes for gene: FGD5 were changed from tetralogy of fallot MONDO:0008542 to Congenital heart disease - MONDO:0005453, FGD5-related
Fetal anomalies v1.532 FGD5 Krithika Murali Publications for gene: FGD5 were set to 32037394; 30232381
Fetal anomalies v1.531 FGD5 Krithika Murali Classified gene: FGD5 as Amber List (moderate evidence)
Fetal anomalies v1.531 FGD5 Krithika Murali Gene: fgd5 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.528 FGD5 Krithika Murali Phenotypes for gene: FGD5 were changed from Congenital heart disease - MONDO:0005453, FGD5-related to Congenital heart disease - MONDO:0005453, FGD5-related
Congenital Heart Defect v0.527 FGD5 Krithika Murali Phenotypes for gene: FGD5 were changed from tetralogy of fallot MONDO:0008542 to Congenital heart disease - MONDO:0005453, FGD5-related
Congenital Heart Defect v0.527 FGD5 Krithika Murali Publications for gene: FGD5 were set to 41574350; 41199744; 32037394; 30232381
Congenital Heart Defect v0.526 FGD5 Krithika Murali Publications for gene: FGD5 were set to 32037394; 30232381
Congenital Heart Defect v0.526 FGD5 Krithika Murali Classified gene: FGD5 as Amber List (moderate evidence)
Congenital Heart Defect v0.526 FGD5 Krithika Murali Gene: fgd5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.530 Krithika Murali Added reviews for gene FGD5 from panel Mendeliome
Mendeliome v1.4339 FGD5 Krithika Murali Phenotypes for gene: FGD5 were changed from tetralogy of fallot MONDO:0008542 to Congenital heart disease - MONDO:0005453, FGD5-related
Mendeliome v1.4338 FGD5 Krithika Murali Publications for gene: FGD5 were set to 32037394; 30232381
Fetal anomalies v1.529 Krithika Murali Copied gene FGD5 from panel Mendeliome
Fetal anomalies v1.529 FGD5 Krithika Murali gene: FGD5 was added
gene: FGD5 was added to Fetal anomalies. Sources: Expert Review Red,Literature
Mode of inheritance for gene: FGD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGD5 were set to 32037394; 30232381
Phenotypes for gene: FGD5 were set to tetralogy of fallot MONDO:0008542
Congenital Heart Defect v0.525 Krithika Murali Added reviews for gene FGD5 from panel Mendeliome
Mendeliome v1.4337 FGD5 Krithika Murali Classified gene: FGD5 as Amber List (moderate evidence)
Mendeliome v1.4337 FGD5 Krithika Murali Gene: fgd5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4336 FGD5 Krithika Murali reviewed gene: FGD5: Rating: AMBER; Mode of pathogenicity: None; Publications: 41574350, 41199744, 32037394, 30232381; Phenotypes: Congenital heart disease - MONDO:0005453, FGD5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.668 FSCN1 Lilian Downie reviewed gene: FSCN1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 40874942; Phenotypes: neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4336 RNF213 Michelle Torres changed review comment from: The well-know East Asian founder variant, p.(Arg4810Lys) (aka p.(Arg4859Lys)), has been reported in multiple homozygous individuals with moyamoya disease. In a Japanese cohort, homozygous individuals had a significantly earlier age at onset compared with heterozygotes (PMID: 22377813).

The evidence for AR as a MOI in association with other variants is not convincing (PMIDs: 30922903, 33960657).; to: The well-know East Asian founder variant, p.(Arg4810Lys) (aka p.(Arg4859Lys)), has been reported in multiple homozygous individuals with moyamoya disease. In a Japanese cohort, homozygous individuals had a significantly earlier age at onset compared with heterozygotes (PMID: 22377813).

The evidence for AR as a MOI in association with other variants is not convincing (PMIDs: 30922903, 33960657).

*Specific MONDO for this gene is Moyamoya disease 2 (MONDO:0011784).
Mendeliome v1.4336 RNF213 Michelle Torres reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: 22377813, 30922903, 33960657; Phenotypes: Moyamoya disease 2, susceptibility to MIM#607151; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Ciliary Dyskinesia v1.74 NME5 Lucy Spencer Phenotypes for gene: NME5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 48, without situs inversus MIM#620032
Deafness_IsolatedAndComplex v1.325 TBC1D8 Sangavi Sivagnanasundram Mode of inheritance for gene: TBC1D8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v1.73 NME5 Lucy Spencer Publications for gene: NME5 were set to PMID: 32185794
Deafness_IsolatedAndComplex v1.324 TBC1D8 Sangavi Sivagnanasundram Phenotypes for gene: TBC1D8 were changed from Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372 to non-syndromic hearing loss MONDO:0019587
Ciliary Dyskinesia v1.72 NME5 Lucy Spencer Classified gene: NME5 as Green List (high evidence)
Ciliary Dyskinesia v1.72 NME5 Lucy Spencer Gene: nme5 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.323 TBC1D8 Sangavi Sivagnanasundram Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Deafness_IsolatedAndComplex v1.322 TBC1D8 Sangavi Sivagnanasundram Classified gene: TBC1D8 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.322 TBC1D8 Sangavi Sivagnanasundram Gene: tbc1d8 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.321 TBC1D8 Sangavi Sivagnanasundram edited their review of gene: TBC1D8: Changed rating: RED; Changed publications: 35248088; Changed phenotypes: non-syndromic hearing loss MONDO:0019587; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v1.90 TBC1D8 Sangavi Sivagnanasundram Phenotypes for gene: TBC1D8 were changed from Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372 to non obstructive azoospermia or cryptozoospermia MONDO:0005372
Deafness_IsolatedAndComplex v1.321 Sangavi Sivagnanasundram Copied gene TBC1D8 from panel Mendeliome
Deafness_IsolatedAndComplex v1.321 TBC1D8 Sangavi Sivagnanasundram gene: TBC1D8 was added
gene: TBC1D8 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TBC1D8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Phenotypes for gene: TBC1D8 were set to Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372
Infertility and Recurrent Pregnancy Loss v1.89 TBC1D8 Sangavi Sivagnanasundram Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Infertility and Recurrent Pregnancy Loss v1.88 TBC1D8 Sangavi Sivagnanasundram Mode of inheritance for gene: TBC1D8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.87 TBC1D8 Sangavi Sivagnanasundram edited their review of gene: TBC1D8: Changed publications: 41556581; Changed phenotypes: non obstructive azoospermia or cryptozoospermia MONDO:0005372; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v1.87 Sangavi Sivagnanasundram Copied gene TBC1D8 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.87 TBC1D8 Sangavi Sivagnanasundram gene: TBC1D8 was added
gene: TBC1D8 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TBC1D8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Phenotypes for gene: TBC1D8 were set to Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372
Ciliary Dyskinesia v1.71 Lucy Spencer Added reviews for gene NME5 from panel Mendeliome
Mendeliome v1.4336 NME5 Lucy Spencer Phenotypes for gene: NME5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 48, without situs inversus MIM#620032
Mendeliome v1.4335 NME5 Lucy Spencer Publications for gene: NME5 were set to 32185794
Mendeliome v1.4334 NME5 Lucy Spencer Classified gene: NME5 as Green List (high evidence)
Mendeliome v1.4334 NME5 Lucy Spencer Gene: nme5 has been classified as Green List (High Evidence).
Mendeliome v1.4333 NME5 Lucy Spencer reviewed gene: NME5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32185794, 33635012, 37296588, 37998386, 37957793, 41499646; Phenotypes: Ciliary dyskinesia, primary, 48, without situs inversus MIM#620032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4333 TBC1D8 Sangavi Sivagnanasundram Classified gene: TBC1D8 as Green List (high evidence)
Mendeliome v1.4333 TBC1D8 Sangavi Sivagnanasundram Gene: tbc1d8 has been classified as Green List (High Evidence).
Mendeliome v1.4332 TBC1D8 Sangavi Sivagnanasundram Classified gene: TBC1D8 as Green List (high evidence)
Mendeliome v1.4332 TBC1D8 Sangavi Sivagnanasundram Gene: tbc1d8 has been classified as Green List (High Evidence).
Mendeliome v1.4331 TBC1D8 Sangavi Sivagnanasundram gene: TBC1D8 was added
gene: TBC1D8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBC1D8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBC1D8 were set to 41556581; 35248088; 33584793
Phenotypes for gene: TBC1D8 were set to Lennox‑Gastaut syndrome MONDO:0016532; non-syndromic hearing loss MONDO:0019587; non obstructive azoospermia or cryptozoospermia MONDO:0005372
Review for gene: TBC1D8 was set to GREEN
Added comment: GREEN AR - non-obstructive azoospermia or cryptozoospermia
RED AD - Lennox‑Gastaut syndrome and non-syndromic hearing loss

PMID: 41556581 - Two affected unrelated individuals with biallelic variants
Immunofluorescence staining showed decreased protein expression in the testis of the affected individual compared to that of a fertile individual.

PMID:35248088 - AD non-syndromic hearing loss
De novo heterozygous missense variant in one individual presenting with hearing loss
p.Ser666Leu - GrpMax FAF = 0.2%

PMID: 33584793 - AD Lennox‑Gastaut syndrome
12yrM presented with tonic, atonic seizures however had normal MRI
Assumed de novo missense variant identified
Sources: Literature
Mendeliome v1.4330 ATP11C Lucy Spencer Publications for gene: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Mendeliome v1.4329 ATP11C Lucy Spencer edited their review of gene: ATP11C: Changed publications: 41523080, 40869043, 37892263, 37671681, 26944472, 37314652
Mendeliome v1.4329 ATP11C Lucy Spencer changed review comment from: PMID: 40869043 reports 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.
Sources: Literature; to: PMID: 40869043 reports 4 patients from 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1. Studies in patient RBS for all 4 patients showed reduced flippase activity.

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.

PMID: 37314652 One hemizygous male with a frameshift in ATP11C and agranulocytosis, recurrent acute liver failure and developmental delay. Previously published mouse models deficient in ATP11C displayed conjugated hyperbilirubinemia, hyperchloremia, and hemolytic anemia.
Sources: Literature
Red cell disorders v1.46 Lucy Spencer Copied gene ATP11C from panel Mendeliome
Red cell disorders v1.46 ATP11C Lucy Spencer gene: ATP11C was added
gene: ATP11C was added to Red cell disorders. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ATP11C 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: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Phenotypes for gene: ATP11C were set to Hemolytic anemia, congenital, X-linked MIM#301015
Mendeliome v1.4329 ATP11C Lucy Spencer Classified gene: ATP11C as Amber List (moderate evidence)
Mendeliome v1.4329 ATP11C Lucy Spencer Gene: atp11c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4328 ATP11C Lucy Spencer gene: ATP11C was added
gene: ATP11C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP11C 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: ATP11C were set to 41523080; 40869043; 37892263; 37671681; 26944472
Phenotypes for gene: ATP11C were set to Hemolytic anemia, congenital, X-linked MIM#301015
Review for gene: ATP11C was set to AMBER
Added comment: PMID: 40869043 reports 3 unrelated families with haemolytic anaemia and ATP11C variants. Probands were all hemizygous boys who had maternally inherited variants, all variants were absent or only has 1 het in gnomad. One family had a frameshift, another ha 2 missense variants in cis, and the third had a -7 splice variant that RT-PCR showed resulted in an in frame insertion. 2 probands were shown to have normal G6PD activity and haemoglobin, the third was not tested. The proband with the ATP11C frameshift also had a de novo missense in ANK1

PMID: 37892263, 37671681, 26944472 report 3 hemizygous male haemolytic anaemia. However 2 of the patients had pathogenic variants in genes associated with spherocytosis SPTA1 and ANK1. The ATP11C variants were absent or rare in gnomad (note papers use different transcripts/p. numbering to gnomad).

PMID: 41523080 reports 2 of the same patients as PMID:40869043 and additionally looked at Val972Met in a very large cohort of blood donors, but this variant is called Val969Met in gnomad where it has thousands of hets and hemizygotes.
Sources: Literature
Incidentalome v0.423 Bryony Thompson Copied gene BARD1 from panel Breast Cancer
Incidentalome v0.423 BARD1 Bryony Thompson gene: BARD1 was added
gene: BARD1 was added to Incidentalome. Sources: Expert Review Green,Expert Review,Expert list
Mode of inheritance for gene: BARD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BARD1 were set to Breast cancer, MONDO:0007254; BARD1-related cancer predisposition, MONDO:0700267; Breast cancer, susceptibility to, MIM#114480
Mendeliome v1.4327 GPR101 Bryony Thompson Marked gene: GPR101 as ready
Mendeliome v1.4327 GPR101 Bryony Thompson Gene: gpr101 has been classified as Green List (High Evidence).
Mendeliome v1.4327 GPR101 Bryony Thompson changed review comment from: Well-established gene-disease association with a GeneReviews. Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature; to: Well-established gene-disease association with X-Linked Acrogigantism (has a GeneReviews). Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature
Mendeliome v1.4327 GPR101 Bryony Thompson Classified gene: GPR101 as Green List (high evidence)
Mendeliome v1.4327 GPR101 Bryony Thompson Gene: gpr101 has been classified as Green List (High Evidence).
Mendeliome v1.4326 GPR101 Bryony Thompson gene: GPR101 was added
gene: GPR101 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR101 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: GPR101 were set to 29389097
Phenotypes for gene: GPR101 were set to pituitary adenoma, growth hormone-secreting, 2 MONDO:0010492
Review for gene: GPR101 was set to GREEN
Added comment: Well-established gene-disease association with a GeneReviews. Heterozygous or hemizygous for a germline variant or somatic duplication.
Sources: Literature
Mendeliome v1.4325 MID2 Bryony Thompson gene: MID2 was added
gene: MID2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MID2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MID2 were set to 24115387
Phenotypes for gene: MID2 were set to non-syndromic X-linked intellectual disability MONDO:0019181
Review for gene: MID2 was set to RED
Added comment: A single family reported
Sources: Literature
Mendeliome v1.4324 HMGB3 Bryony Thompson Marked gene: HMGB3 as ready
Mendeliome v1.4324 HMGB3 Bryony Thompson Gene: hmgb3 has been classified as Red List (Low Evidence).
Mendeliome v1.4324 HMGB3 Bryony Thompson gene: HMGB3 was added
gene: HMGB3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGB3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HMGB3 were set to 24993872
Phenotypes for gene: HMGB3 were set to X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome MONDO:0010485
Review for gene: HMGB3 was set to RED
Added comment: A single family reported in 2014, segregating a hemizygous frameshift variant in affected men
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.86 Bryony Thompson Copied gene TTC29 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.86 TTC29 Bryony Thompson gene: TTC29 was added
gene: TTC29 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TTC29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC29 were set to 31735292
Phenotypes for gene: TTC29 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4323 TTC29 Bryony Thompson Marked gene: TTC29 as ready
Mendeliome v1.4323 TTC29 Bryony Thompson Gene: ttc29 has been classified as Green List (High Evidence).
Mendeliome v1.4323 TTC29 Bryony Thompson Classified gene: TTC29 as Green List (high evidence)
Mendeliome v1.4323 TTC29 Bryony Thompson Gene: ttc29 has been classified as Green List (High Evidence).
Mendeliome v1.4322 TTC29 Bryony Thompson gene: TTC29 was added
gene: TTC29 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC29 were set to 31735292
Phenotypes for gene: TTC29 were set to spermatogenic failure MONDO:0004983
Review for gene: TTC29 was set to GREEN
Added comment: 5 unrelated men with infertility and a supporting null mouse model
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.85 Bryony Thompson Copied gene CCDC146 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.85 CCDC146 Bryony Thompson gene: CCDC146 was added
gene: CCDC146 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CCDC146 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC146 were set to 38441556; 39245651
Phenotypes for gene: CCDC146 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4321 CCDC146 Bryony Thompson Marked gene: CCDC146 as ready
Mendeliome v1.4321 CCDC146 Bryony Thompson Gene: ccdc146 has been classified as Green List (High Evidence).
Mendeliome v1.4321 CCDC146 Bryony Thompson Classified gene: CCDC146 as Green List (high evidence)
Mendeliome v1.4321 CCDC146 Bryony Thompson Gene: ccdc146 has been classified as Green List (High Evidence).
Mendeliome v1.4320 CCDC146 Bryony Thompson gene: CCDC146 was added
gene: CCDC146 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC146 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC146 were set to 38441556; 39245651
Phenotypes for gene: CCDC146 were set to spermatogenic failure MONDO:0004983
Review for gene: CCDC146 was set to GREEN
Added comment: 3 males with biallelic variants and a supporting infertile mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.84 Bryony Thompson Copied gene ARMC12 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.84 ARMC12 Bryony Thompson gene: ARMC12 was added
gene: ARMC12 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ARMC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC12 were set to 35534203; 33536340
Phenotypes for gene: ARMC12 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4319 ARMC12 Bryony Thompson Marked gene: ARMC12 as ready
Mendeliome v1.4319 ARMC12 Bryony Thompson Gene: armc12 has been classified as Green List (High Evidence).
Mendeliome v1.4319 ARMC12 Bryony Thompson Classified gene: ARMC12 as Green List (high evidence)
Mendeliome v1.4319 ARMC12 Bryony Thompson Gene: armc12 has been classified as Green List (High Evidence).
Mendeliome v1.4318 ARMC12 Bryony Thompson gene: ARMC12 was added
gene: ARMC12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARMC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC12 were set to 35534203; 33536340
Phenotypes for gene: ARMC12 were set to spermatogenic failure MONDO:0004983
Review for gene: ARMC12 was set to GREEN
Added comment: 3 males from 2 families with hom/chet variants and a supporting null mouse model.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.83 Bryony Thompson Copied gene CFAP61 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.83 CFAP61 Bryony Thompson gene: CFAP61 was added
gene: CFAP61 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CFAP61 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP61 were set to 36659204; 34792097; 35387802; 35174165
Phenotypes for gene: CFAP61 were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4317 CFAP61 Bryony Thompson Marked gene: CFAP61 as ready
Mendeliome v1.4317 CFAP61 Bryony Thompson Gene: cfap61 has been classified as Green List (High Evidence).
Mendeliome v1.4317 CFAP61 Bryony Thompson Classified gene: CFAP61 as Green List (high evidence)
Mendeliome v1.4317 CFAP61 Bryony Thompson Gene: cfap61 has been classified as Green List (High Evidence).
Mendeliome v1.4316 CFAP61 Bryony Thompson gene: CFAP61 was added
gene: CFAP61 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP61 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP61 were set to 36659204; 34792097; 35387802; 35174165
Phenotypes for gene: CFAP61 were set to spermatogenic failure MONDO:0004983
Review for gene: CFAP61 was set to GREEN
Added comment: At least 6 unrelated men with chet/hom variants and a supporting mouse model
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.82 Bryony Thompson Copied gene NUP210L from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.82 NUP210L Bryony Thompson gene: NUP210L was added
gene: NUP210L was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NUP210L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP210L were set to 20034429; 33332558
Phenotypes for gene: NUP210L were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4315 NUP210L Bryony Thompson Marked gene: NUP210L as ready
Mendeliome v1.4315 NUP210L Bryony Thompson Gene: nup210l has been classified as Red List (Low Evidence).
Mendeliome v1.4315 NUP210L Bryony Thompson gene: NUP210L was added
gene: NUP210L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP210L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP210L were set to 20034429; 33332558
Phenotypes for gene: NUP210L were set to spermatogenic failure MONDO:0004983
Review for gene: NUP210L was set to RED
Added comment: Single case from a consanguineous family and a supporting null mouse model.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v1.8 PTPN2 Bryony Thompson Marked gene: PTPN2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v1.8 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.8 PTPN2 Bryony Thompson Classified gene: PTPN2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v1.8 PTPN2 Bryony Thompson Gene: ptpn2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v1.7 PTPN2 Bryony Thompson gene: PTPN2 was added
gene: PTPN2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: PTPN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN2 were set to 41545210; 39028869; 39959585
Phenotypes for gene: PTPN2 were set to Inborn error of immunity, MONDO:0003778
Review for gene: PTPN2 was set to GREEN
gene: PTPN2 was marked as current diagnostic
Added comment: 3 cases (2 de novo and 1 likely de novo but father unavailable for testing) with interstitial lung disease as a feature of the phenotype. Variants are associated with reduced PTPN2 expression.
Sources: Literature
Mendeliome v1.4314 PTPN2 Bryony Thompson Publications for gene: PTPN2 were set to 32499645; 27658548; 39028869
Mendeliome v1.4313 PTPN2 Bryony Thompson edited their review of gene: PTPN2: Added comment: 2 consanguineous cases with homozygous missense variants in PTPN2 (heterozygous individuals unaffected). Phenotypes differ between common variable immunodeficiency with bronchiectasis, or early‑onset Crohn disease with growth failure and neurodevelopmental delay.; Changed rating: RED; Changed publications: 37537852, 35389161; Changed phenotypes: Inborn error of immunity, MONDO:0003778, Syndromic disease, MONDO:0002254; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.42 RAPGEF2 Bryony Thompson Marked gene: RAPGEF2 as ready
Motor Neurone Disease v1.42 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Red List (Low Evidence).
Motor Neurone Disease v1.42 RAPGEF2 Bryony Thompson Classified gene: RAPGEF2 as Red List (low evidence)
Motor Neurone Disease v1.42 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Red List (Low Evidence).
Motor Neurone Disease v1.41 RAPGEF2 Bryony Thompson changed review comment from: Red for ALS & green for neurodevelopmental disorder
PMID: 30636905 - single individual with early‑onset ALS and a de novo missense gain‑of‑function variant
PMID: 41556274 - 5 unrelated individuals with a childhood‑onset neurodevelopmental disorder with de novo likely haploinsufficient loss‑of‑function variants.; to: A single individual with early‑onset ALS and a de novo missense gain‑of‑function variant
Motor Neurone Disease v1.41 RAPGEF2 Bryony Thompson edited their review of gene: RAPGEF2: Changed rating: RED; Changed publications: 30636905; Changed phenotypes: amyotrophic lateral sclerosis MONDO:0004976
Motor Neurone Disease v1.41 Bryony Thompson Copied gene RAPGEF2 from panel Mendeliome
Motor Neurone Disease v1.41 RAPGEF2 Bryony Thompson gene: RAPGEF2 was added
gene: RAPGEF2 was added to Motor Neurone Disease. Sources: Expert Review Green,Literature
STR tags were added to gene: RAPGEF2.
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 41556274; 30636905
Phenotypes for gene: RAPGEF2 were set to Neurodevelopmental disorder, MONDO:0700092; amyotrophic lateral sclerosis MONDO:0004976
Intellectual disability syndromic and non-syndromic v1.668 Bryony Thompson Copied gene RAPGEF2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.668 RAPGEF2 Bryony Thompson gene: RAPGEF2 was added
gene: RAPGEF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
STR tags were added to gene: RAPGEF2.
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 41556274; 30636905
Phenotypes for gene: RAPGEF2 were set to Neurodevelopmental disorder, MONDO:0700092; amyotrophic lateral sclerosis MONDO:0004976
Mendeliome v1.4313 Bryony Thompson Copied STR RAPGEF2_FAME7_TTTCA from panel Genetic Epilepsy
Mendeliome v1.4313 RAPGEF2_FAME7_TTTCA Bryony Thompson STR: RAPGEF2_FAME7_TTTCA was added
STR: RAPGEF2_FAME7_TTTCA was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for STR: RAPGEF2_FAME7_TTTCA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: RAPGEF2_FAME7_TTTCA were set to 29507423; 30351492; 33791773
Phenotypes for STR: RAPGEF2_FAME7_TTTCA were set to Epilepsy, familial adult myoclonic, 7 MIM#618075
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Marked gene: RAPGEF2 as ready
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Green List (High Evidence).
Mendeliome v1.4312 RAPGEF2 Bryony Thompson Phenotypes for gene: RAPGEF2 were changed from ?Epilepsy, familial adult myoclonic, 7 MIM# 618075 to Neurodevelopmental disorder, MONDO:0700092; amyotrophic lateral sclerosis MONDO:0004976
Mendeliome v1.4311 RAPGEF2 Bryony Thompson Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Mendeliome v1.4310 RAPGEF2 Bryony Thompson Classified gene: RAPGEF2 as Green List (high evidence)
Mendeliome v1.4310 RAPGEF2 Bryony Thompson Gene: rapgef2 has been classified as Green List (High Evidence).
Mendeliome v1.4309 RAPGEF2 Bryony Thompson reviewed gene: RAPGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41556274, 30636905; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, amyotrophic lateral sclerosis MONDO:0004976; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Lipodystrophy_Lipoatrophy v1.42 EBF2 Zornitza Stark Marked gene: EBF2 as ready
Lipodystrophy_Lipoatrophy v1.42 EBF2 Zornitza Stark Gene: ebf2 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v1.42 EBF2 Zornitza Stark Mode of inheritance for gene: EBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy_Lipoatrophy v1.41 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4309 EBF2 Zornitza Stark Mode of inheritance for gene: EBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4308 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lipodystrophy_Lipoatrophy v1.41 Zornitza Stark Copied gene EBF2 from panel Mendeliome
Lipodystrophy_Lipoatrophy v1.41 EBF2 Zornitza Stark gene: EBF2 was added
gene: EBF2 was added to Lipodystrophy_Lipoatrophy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: EBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EBF2 were set to 41615236; 38978649; 29704291
Phenotypes for gene: EBF2 were set to Lipodystrophy, MONDO:0006573, EBF2-related
Mendeliome v1.4308 EBF2 Zornitza Stark Classified gene: EBF2 as Amber List (moderate evidence)
Mendeliome v1.4308 EBF2 Zornitza Stark Gene: ebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed rating: AMBER
Mendeliome v1.4307 EBF2 Zornitza Stark Marked gene: EBF2 as ready
Mendeliome v1.4307 EBF2 Zornitza Stark Gene: ebf2 has been classified as Red List (Low Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark gene: EBF2 was added
gene: EBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EBF2 were set to 41615236; 38978649; 29704291
Phenotypes for gene: EBF2 were set to Lipodystrophy, MONDO:0006573, EBF2-related
Review for gene: EBF2 was set to RED
Added comment: PMIDs 38978649 and 41615236 each describe a single patient with a heterozygous nonsense p.Glu165Ter variant and childhood‑onset partial lipodystrophy, providing extensive functional validation. Heterozygous knock‑in mice (Ebf2^E165X/+) recapitulate restricted adipogenesis, extracellular matrix fibrosis, reduced leptin and adiponectin, metabolic impairment on high‑fat diet and mitochondrial gene down‑regulation, supporting pathogenicity. Dominant negative mechanism suggested.

Also note PMID 29704291 reports six affected individuals from one family with a heterozygous missense p.Ala72Val variant and isolated imperforate anus. No functional data provided.
Sources: Literature
Cerebral Palsy v1.410 SLC6A3 Lucy Spencer Classified gene: SLC6A3 as Green List (high evidence)
Cerebral Palsy v1.410 SLC6A3 Lucy Spencer Gene: slc6a3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.409 SLC6A3 Lucy Spencer gene: SLC6A3 was added
gene: SLC6A3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC6A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A3 were set to 33528536; 21112253; 33098801
Phenotypes for gene: SLC6A3 were set to Parkinsonism-dystonia, infantile, 1 MIM#613135
Review for gene: SLC6A3 was set to GREEN
Added comment: PMID: 21112253 presents a clinical overview of 11 children with biallelic SLC6A3 mutations, 7 of which were initially diagnosed with CP. In addition, two more CP cohort studies with one patient each harboring SLC6A3 mutations.

This review was originally entered for SLC5A6 in error and has now been moved here
Sources: Literature
Cerebral Palsy v1.408 Lucy Spencer removed gene:SLC5A6 from the panel
Cardiomyopathy_Paediatric v0.219 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Cardiomyopathy_Paediatric v0.219 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.219 FARS2 Zornitza Stark Classified gene: FARS2 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.219 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.218 FARS2 Zornitza Stark gene: FARS2 was added
gene: FARS2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARS2 were set to 33168986; 38362779; 41588148; 34690748
Phenotypes for gene: FARS2 were set to Combined oxidative phosphorylation deficiency MIM#614946
Review for gene: FARS2 was set to GREEN
Added comment: Cardiomyopathy is part of the phenotype.
Sources: Literature
Skeletal dysplasia v0.413 FAM111A Zornitza Stark Marked gene: FAM111A as ready
Skeletal dysplasia v0.413 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.413 FAM111A Zornitza Stark Publications for gene: FAM111A were set to
Skeletal dysplasia v0.412 FAM111A Zornitza Stark Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.411 FAM111A Zornitza Stark reviewed gene: FAM111A: Rating: AMBER; Mode of pathogenicity: None; Publications: 39932783, 39501122; Phenotypes: Kenny-Caffey syndrome, type 2, MIM# 127000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4306 FAM111A Zornitza Stark Phenotypes for gene: FAM111A were changed from autosomal dominant Kenny-Caffey syndrome MONDO:0007478 to Kenny-Caffey syndrome, type 2, MIM# 127000
Mendeliome v1.4305 FAM111A Zornitza Stark Publications for gene: FAM111A were set to 23684011; 32996714; 32765931; 33010201
Mendeliome v1.4304 FAM111A Zornitza Stark Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4303 FAM111A Zornitza Stark reviewed gene: FAM111A: Rating: AMBER; Mode of pathogenicity: None; Publications: 39932783, 39501122; Phenotypes: Kenny-Caffey syndrome, type 2, MIM# 127000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.54 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863; 25515317; 26675350
Metal Metabolism Disorders v0.53 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.52 STEAP3 Zornitza Stark edited their review of gene: STEAP3: Added comment: PMID 38360212 reports two unrelated families with compound heterozygous STEAP3 missense variants (p.I177M, p.T495M) causing childhood-onset microcytic anaemia; functional ferrireductase assays in HeLa cells demonstrate loss of activity. Part of large cohort study, low level of individual detail.; Changed publications: 22031863, 25515317, 26675350, 38360212; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.45 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863; 25515317; 26675350
Red cell disorders v1.44 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.43 STEAP3 Zornitza Stark edited their review of gene: STEAP3: Added comment: PMID 38360212 reports two unrelated families with compound heterozygous STEAP3 missense variants (p.I177M, p.T495M) causing childhood-onset microcytic anaemia; functional ferrireductase assays in HeLa cells demonstrate loss of activity. Part of large cohort study, low level of individual detail.; Changed publications: 22031863, 25515317, 26675350, 38360212; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4303 STEAP3 Zornitza Stark Publications for gene: STEAP3 were set to 22031863; 25515317; 26675350
Mendeliome v1.4302 STEAP3 Zornitza Stark Mode of inheritance for gene: STEAP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4301 STEAP3 Zornitza Stark edited their review of gene: STEAP3: Added comment: PMID 38360212 reports two unrelated families with compound heterozygous STEAP3 missense variants (p.I177M, p.T495M) causing childhood-onset microcytic anaemia; functional ferrireductase assays in HeLa cells demonstrate loss of activity. Part of large cohort study, low level of individual detail.; Changed publications: 22031863, 25515317, 26675350, 38360212; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4301 TRU-TCA1-1 Katrina Bell All sources for gene: TRU-TCA1-1 were removed
Fetal anomalies v1.528 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from Neurodevelopmental disorder (MONDO:0700092), PTBP1-related to STAD syndrome, MIM# 621495
Fetal anomalies v1.527 PTBP1 Zornitza Stark reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: STAD syndrome, MIM# 621495; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.411 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from Neurodevelopmental disorder (MONDO:0700092), PTBP1-related to STAD syndrome, MIM# 621495
Skeletal dysplasia v0.410 PTBP1 Zornitza Stark reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: STAD syndrome, MIM# 621495; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.667 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from Neurodevelopmental disorder (MONDO:0700092), PTBP1-related to STAD syndrome, MIM# 621495
Intellectual disability syndromic and non-syndromic v1.666 PTBP1 Zornitza Stark reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: STAD syndrome, MIM# 621495; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4300 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from Neurodevelopmental disorder (MONDO:0700092), PTBP1-related to STAD syndrome, MIM# 621495
Mendeliome v1.4299 PTBP1 Zornitza Stark reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: STAD syndrome, MIM# 621495; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia and Chorea v0.338 ATP5B Zornitza Stark Marked gene: ATP5B as ready
Dystonia and Chorea v0.338 ATP5B Zornitza Stark Gene: atp5b has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.338 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Inherited dystonia, MONDO:0044807, ATP5B-related to Dystonia 38, susceptibility to, MIM# 621502
Mitochondrial disease v1.15 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Dystonia 38, susceptibility to, MIM# 621502; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085 to Dystonia 38, susceptibility to, MIM# 621502; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Dystonia and Chorea v0.337 ATP5B Zornitza Stark edited their review of gene: ATP5B: Changed phenotypes: Dystonia 38, susceptibility to, MIM# 621502, Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mitochondrial disease v1.15 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Inherited dystonia, MONDO:0044807, ATP5B-related; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085 to Dystonia 38, susceptibility to, MIM# 621502; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mitochondrial disease v1.14 ATP5B Zornitza Stark edited their review of gene: ATP5B: Changed phenotypes: Dystonia 38, susceptibility to, MIM# 621502, Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4299 ATP5B Zornitza Stark Phenotypes for gene: ATP5B were changed from Inherited dystonia, MONDO:0044807, ATP5B-related; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085 to Dystonia 38, susceptibility to, MIM# 621502; Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Mendeliome v1.4298 ATP5B Zornitza Stark edited their review of gene: ATP5B: Changed phenotypes: Dystonia 38, susceptibility to, MIM# 621502, Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, MIM# 620085
Osteopetrosis v1.0 CLCN7 Sangavi Sivagnanasundram changed review comment from: Both AD and AR GDA has been classified as DEFINITIVE by ClinGen Skeletal Dysplasia GCEP in 2023

AD - https://search.clinicalgenome.org/CCID:004466
AR - https://search.clinicalgenome.org/CCID:004467; to: Both AD and AR GDA has been classified as DEFINITIVE by ClinGen Skeletal Dysplasia GCEP in 2023

AD - https://search.clinicalgenome.org/CCID:004466 - Dominant negative MOD
AR - https://search.clinicalgenome.org/CCID:004467 - Loss of function MOD
Osteopetrosis v1.0 CLCN7 Sangavi Sivagnanasundram reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal dominant osteopetrosis 2 MONDO:0008156, autosomal recessive osteopetrosis 4 MONDO:0012676; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
IBMDx study v0.41 GP1BB Zornitza Stark Marked gene: GP1BB as ready
IBMDx study v0.41 GP1BB Zornitza Stark Gene: gp1bb has been classified as Green List (High Evidence).
IBMDx study v0.41 GP1BB Zornitza Stark Phenotypes for gene: GP1BB were changed from Bernard-Soulier syndrome (BSS) to ulier syndrome, type B, MIM# 231200; Macrothrombocytopaenia
IBMDx study v0.40 GP1BB Zornitza Stark Publications for gene: GP1BB were set to
IBMDx study v0.39 GP1BB Zornitza Stark Mode of inheritance for gene: GP1BB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4298 GDF3 Zornitza Stark Phenotypes for gene: GDF3 were changed from Microphthalmia with coloboma 6, MIM# 613703; Microphthalmia, isolated 7, MIM# 613704 to Microphthalmia with coloboma 6, MIM# 613703; Microphthalmia, isolated 7, MIM# 613704; Klippel-Feil anomaly with laryngeal malformation - 613702
Mendeliome v1.4297 GDF3 Zornitza Stark edited their review of gene: GDF3: Added comment: Single family reported with the skeletal phenotype in 2010, none since. Note they also had ocular abnormalities so unclear if this is a distinct association.; Changed phenotypes: Microphthalmia with coloboma 6 613703, Microphthalmia, isolated 7 613704, Klippel-Feil anomaly with laryngeal malformation - 613702
Skeletal dysplasia v0.410 GDF3 Zornitza Stark Marked gene: GDF3 as ready
Skeletal dysplasia v0.410 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.410 GDF3 Zornitza Stark Deleted their comment
Skeletal dysplasia v0.410 GDF3 Zornitza Stark edited their review of gene: GDF3: Added comment: Single family reported in 2010 with this phenotype, none since. Note ocular abnormalities also present so unsure if this is a distinct disorder.; Changed phenotypes: Klippel-Feil anomaly with laryngeal malformation - 613702
Skeletal dysplasia v0.410 GDF3 Zornitza Stark Mode of inheritance for gene: GDF3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.409 GDF3 Zornitza Stark edited their review of gene: GDF3: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4297 GDF3 Zornitza Stark Mode of inheritance for gene: GDF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4296 GDF3 Zornitza Stark edited their review of gene: GDF3: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.378 ZFHX3 Zornitza Stark Phenotypes for gene: ZFHX3 were changed from developmental and epileptic encephalopathy MONDO:0100062 to {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500
Genetic Epilepsy v1.377 ZFHX3 Zornitza Stark reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500; Mode of inheritance: None
Mendeliome v1.4296 ZFHX3 Zornitza Stark Phenotypes for gene: ZFHX3 were changed from Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related; developmental and epileptic encephalopathy MONDO:0100062, ZFHX3-related to Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related; {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500
Mendeliome v1.4295 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related, {Epilepsy, idiopathic generalized, susceptibility to}, MIM#621500
Mendeliome v1.4295 PTPRF Bryony Thompson gene: PTPRF was added
gene: PTPRF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPRF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPRF were set to 24781087
Phenotypes for gene: PTPRF were set to breasts and/or nipples, aplasia or hypoplasia of, 2 MONDO:0014450
Review for gene: PTPRF was set to RED
Added comment: A single consanguineous family with a homozygous variant
Sources: Literature
Incidentalome v0.422 PLA2G2A Bryony Thompson gene: PLA2G2A was added
gene: PLA2G2A was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: PLA2G2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLA2G2A were set to 9272153; 8912789
Phenotypes for gene: PLA2G2A were set to colorectal cancer MONDO:0005575
Review for gene: PLA2G2A was set to RED
Added comment: Single case reported with a frameshift variant (c.144_145del) that has 61 hets present in gnomAD.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.666 PRODH Krithika Murali Classified gene: PRODH as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.666 PRODH Krithika Murali Gene: prodh has been classified as Amber List (Moderate Evidence).
Autism v0.245 PRODH Krithika Murali Phenotypes for gene: PRODH were changed from to hyperprolinemia type 1 - MONDO:0009400
Autism v0.245 PRODH Krithika Murali Mode of inheritance for gene: PRODH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Autism v0.245 PRODH Krithika Murali Classified gene: PRODH as Amber List (moderate evidence)
Autism v0.245 PRODH Krithika Murali Gene: prodh has been classified as Amber List (Moderate Evidence).
Autism v0.244 PRODH Krithika Murali Marked gene: PRODH as ready
Autism v0.244 PRODH Krithika Murali Gene: prodh has been classified as Green List (High Evidence).
Genetic Epilepsy v1.377 PRODH Krithika Murali Classified gene: PRODH as Amber List (moderate evidence)
Genetic Epilepsy v1.377 PRODH Krithika Murali Gene: prodh has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.377 PRODH Krithika Murali Publications for gene: PRODH were set to 17412540; 12217952
Genetic Epilepsy v1.376 PRODH Krithika Murali Classified gene: PRODH as Amber List (moderate evidence)
Genetic Epilepsy v1.376 PRODH Krithika Murali Gene: prodh has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.376 PRODH Krithika Murali Classified gene: PRODH as Amber List (moderate evidence)
Genetic Epilepsy v1.376 PRODH Krithika Murali Gene: prodh has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.375 PRODH Krithika Murali reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 34285201, 17412540, 18197084, 12525555; Phenotypes: hyperprolinemia type 1 - MONDO:0009400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.665 PRODH Krithika Murali reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 34285201, 17412540, 18197084, 12525555; Phenotypes: hyperprolinemia type 1 - MONDO:0009400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.244 PRODH Krithika Murali reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 34285201, 17412540, 18197084, 12525555; Phenotypes: hyperprolinemia type 1 - MONDO:0009400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4294 Bryony Thompson Copied gene MYL4 from panel Atrial Fibrillation
Mendeliome v1.4294 MYL4 Bryony Thompson gene: MYL4 was added
gene: MYL4 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYL4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYL4 were set to 27742809; 27066836; 29080865
Phenotypes for gene: MYL4 were set to atrial fibrillation, familial, 18 MONDO:0015001
Atrial Fibrillation v1.6 MYL4 Bryony Thompson Classified gene: MYL4 as Amber List (moderate evidence)
Atrial Fibrillation v1.6 MYL4 Bryony Thompson Gene: myl4 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.5 MYL4 Bryony Thompson gene: MYL4 was added
gene: MYL4 was added to Atrial Fibrillation. Sources: Literature
Mode of inheritance for gene: MYL4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYL4 were set to 27742809; 27066836; 29080865
Phenotypes for gene: MYL4 were set to atrial fibrillation, familial, 18 MONDO:0015001
Review for gene: MYL4 was set to AMBER
Added comment: PMID: 27742809 - MYL4 c.234delC identified homozygous in 8 cases from 5 families with early-onset atrial fibrillation in the Icelandic population. Heterozygous individuals were apparently unaffected.
PMID: 27066836 - heterozygous MYL4 p.Glu11Lys segregates with early-onset atrial fibrillation in a single family. Zebrafish model of the variant (E17K) recapitulated atrial fibrillation.
PMID: 29080865 - rat knock-in model MYL4p.E11K induced fibrotic atrial cardiomyopathy
Sources: Literature
Mendeliome v1.4293 CTSO Rylee Peters gene: CTSO was added
gene: CTSO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTSO was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTSO were set to 41508845
Phenotypes for gene: CTSO were set to Brain aneurysm, MONDO:0005291, CTSO-related
Review for gene: CTSO was set to RED
Added comment: PMID:41508845 reports 9 individuals from 2 unrelated families with heterozygous missense CTSO variants presenting with familial intracranial aneurysm; an additional 8 relatives were heterozygous for a CTSO variant but had no intracranial aneurysm; 16 unaffected relatives did not have a CTSO variant. The two missense variants identified in these families are present in gnomAD v4, p.(Val316Ile) with 84 hets, p.(Ala43Val) with 683 hets, 1 hom.

In‑vitro VSMC knock‑down and mutant‑expression assays showed reduced CTSO secretion, increased fibronectin deposition, increased cell stiffness; but a causal relationship between CTSO variants and intracranial aneurysm has not been demonstrated in an in‑vivo model
Sources: Literature
Mendeliome v1.4292 CELSR1 Rylee Peters changed review comment from: GREEN rating for monoallelic lymphatic malformation 9, MIM# 619319

GREEN rating for biallelic neurodevelopmental disorder association:
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.
PMID: 36453712 describe 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.; to: GREEN rating for monoallelic lymphatic malformation 9, MIM# 619319

GREEN rating for biallelic neurodevelopmental disorder association:
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants associated with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.
PMID: 36453712 describe 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Intellectual disability syndromic and non-syndromic v1.665 CELSR1 Rylee Peters changed review comment from: GREEN rating for biallelic neurodevelopmental disorder association
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature; to: GREEN rating for biallelic neurodevelopmental disorder association
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants associated with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature
Genetic Epilepsy v1.375 CELSR1 Rylee Peters changed review comment from: GREEN rating for biallelic neurodevelopmental disorder association:

PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature; to: GREEN rating for biallelic neurodevelopmental disorder association:

PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants associated with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature
Genetic Epilepsy v1.375 CELSR1 Rylee Peters Classified gene: CELSR1 as Green List (high evidence)
Genetic Epilepsy v1.375 CELSR1 Rylee Peters Gene: celsr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.374 CELSR1 Rylee Peters gene: CELSR1 was added
gene: CELSR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR1 were set to 41530147; 36453712
Phenotypes for gene: CELSR1 were set to Neurodevelopmental disorder (MONDO:0700092), CELSR1-related
Review for gene: CELSR1 was set to GREEN
Added comment: GREEN rating for biallelic neurodevelopmental disorder association:

PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.665 CELSR1 Rylee Peters Phenotypes for gene: CELSR1 were changed from to Neurodevelopmental disorder (MONDO:0700092), CELSR1-related
Intellectual disability syndromic and non-syndromic v1.664 CELSR1 Rylee Peters changed review comment from: PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature; to: GREEN rating for biallelic neurodevelopmental disorder association
PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.664 CELSR1 Rylee Peters Classified gene: CELSR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.664 CELSR1 Rylee Peters Gene: celsr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.663 CELSR1 Rylee Peters gene: CELSR1 was added
gene: CELSR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR1 were set to 41530147; 36453712
Review for gene: CELSR1 was set to GREEN
Added comment: PMID: 41530147 describes 7 individuals from 5 unrelated families with biallelic CELSR1 variants association with brain malformations, neurodevelopmental delay, intellectual disability, behavioural disorders, and 4/7 individuals with epilepsy. Celsr1 knockout mice recapitulate brain malformations and seizure susceptibility. Heterozygous mice were indistinguishable from controls.

PMID: 36453712 describes 4 additional compound heterozygous individuals with epilepsy, 3/4 reported with mild intellectual disability and no abnormalities on brain MRI.
Sources: Literature
Mendeliome v1.4292 CELSR1 Rylee Peters Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9 (MIM#619319); Neurodevelopmental disorder, MONDO:0700092, CELSR1-related
Mendeliome v1.4291 CELSR1 Rylee Peters Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Mendeliome v1.4290 CELSR1 Rylee Peters Mode of inheritance for gene: CELSR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4289 CELSR1 Rylee Peters reviewed gene: CELSR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26855770, 31215153, 31403174, 36453712, 38272662, 41530147; Phenotypes: Lymphatic malformation 9 (MIM#619319), Neurodevelopmental disorder, MONDO:0700092, CELSR1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4289 GPD2 Bryony Thompson Marked gene: GPD2 as ready
Mendeliome v1.4289 GPD2 Bryony Thompson Gene: gpd2 has been classified as Red List (Low Evidence).
Mendeliome v1.4289 GPD2 Bryony Thompson gene: GPD2 was added
gene: GPD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPD2 were set to 9070847; 12093800
Phenotypes for gene: GPD2 were set to type 2 diabetes mellitus MONDO:0005148
Review for gene: GPD2 was set to RED
Added comment: Single case with abnormally low activity of mitochondrial GDH and a rare missense variant. Knockout mouse model has features of both glycerol kinase deficiency and hereditary fructose intolerance.
Sources: Literature
Genetic Epilepsy v1.373 Bryony Thompson Copied gene GAL from panel Mendeliome
Genetic Epilepsy v1.373 GAL Bryony Thompson gene: GAL was added
gene: GAL was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GAL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAL were set to 25691535
Phenotypes for gene: GAL were set to familial temporal lobe epilepsy 8 MONDO:0014650
Mendeliome v1.4288 GAL Bryony Thompson gene: GAL was added
gene: GAL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAL were set to 25691535
Phenotypes for gene: GAL were set to familial temporal lobe epilepsy 8 MONDO:0014650
Review for gene: GAL was set to RED
Added comment: 2 monozygotic male twins with familial temporal lobe epilepsy with a de novo heterozygous missense variant (p.A39E). In vitro functional assay showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.403 SEMA3A Zornitza Stark Classified gene: SEMA3A as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.403 SEMA3A Zornitza Stark Gene: sema3a has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.402 PROK2 Zornitza Stark Classified gene: PROK2 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.402 PROK2 Zornitza Stark Gene: prok2 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.401 KISS1R Zornitza Stark Classified gene: KISS1R as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.401 KISS1R Zornitza Stark Gene: kiss1r has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.400 FGFR1 Zornitza Stark Classified gene: FGFR1 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.400 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.399 FGF8 Zornitza Stark Classified gene: FGF8 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.399 FGF8 Zornitza Stark Gene: fgf8 has been classified as Red List (Low Evidence).
Mendeliome v1.4287 RUNDC1 Zornitza Stark Marked gene: RUNDC1 as ready
Mendeliome v1.4287 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4287 RUNDC1 Zornitza Stark Classified gene: RUNDC1 as Amber List (moderate evidence)
Mendeliome v1.4287 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4286 RUNDC1 Zornitza Stark reviewed gene: RUNDC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.175 RUNDC1 Zornitza Stark Marked gene: RUNDC1 as ready
Pituitary hormone deficiency v0.175 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.175 RUNDC1 Zornitza Stark Classified gene: RUNDC1 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.175 RUNDC1 Zornitza Stark Gene: rundc1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.174 RUNDC1 Zornitza Stark reviewed gene: RUNDC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v1.41 ISCA-46303-Loss Zornitza Stark Marked Region: ISCA-46303-Loss as ready
Differences of Sex Development v1.41 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Differences of Sex Development v1.41 ISCA-46303-Loss Zornitza Stark Phenotypes for Region: ISCA-46303-Loss were changed from to 46XY sex reversal 10, MIM# 616425; 46XX sex reversal 2, MIM# 278850; Pierre-Robin sequence MONDO:0009869, SOX9-related
Differences of Sex Development v1.40 ISCA-46303-Loss Zornitza Stark Classified Region: ISCA-46303-Loss as Green List (high evidence)
Differences of Sex Development v1.40 ISCA-46303-Loss Zornitza Stark Region: isca-46303-loss has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.397 TYMP Zornitza Stark Marked gene: TYMP as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.397 TYMP Zornitza Stark Gene: tymp has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.397 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE); POI; MITOCHONDRIAL DNA DEPLETION SYNDROME 1 to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.396 TYMP Zornitza Stark Classified gene: TYMP as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.396 TYMP Zornitza Stark Gene: tymp has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.395 TYMP Zornitza Stark reviewed gene: TYMP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.395 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.395 WDR11 Zornitza Stark Gene: wdr11 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.395 WDR11 Zornitza Stark Classified gene: WDR11 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.395 WDR11 Zornitza Stark Gene: wdr11 has been classified as Red List (Low Evidence).
Red cell disorders v1.43 STEAP3 Zornitza Stark changed review comment from: Single family reported only with (p.Cys100Ter) variant and a hypomorphic allele; Steap3/Tsap6 null mice model. The 3 siblings presented with transfusion-dependent hypochromic microcytic anaemia with iron overload. Other features present were hepatosplenomegaly, low serum ferritin, and blood smears revealed distinct aniso-poikilocytosis with hypochromasia, microcytosis and ovalocytes.

Conflicting evidence (PMID 26675350): Large Chinese study (of normal and α-thalassemia subjects) investigated the prevalence of STEAP3 mutations in humans and their physiologic consequences. Discovered a relatively high prevalence of potentially harmful recessive alleles. However, whilst the identified STEAP3 mutations exhibited impaired ferrireductase activity in vitro, they had little or no effect on erythrocyte phenotypes; to: Single family reported only with heterozygous (p.Cys100Ter) variant and a hypomorphic allele; Steap3/Tsap6 null mice model. The 3 siblings presented with transfusion-dependent hypochromic microcytic anaemia with iron overload. Other features present were hepatosplenomegaly, low serum ferritin, and blood smears revealed distinct aniso-poikilocytosis with hypochromasia, microcytosis and ovalocytes.

Conflicting evidence (PMID 26675350): Large Chinese study (of normal and α-thalassemia subjects) investigated the prevalence of STEAP3 mutations in humans and their physiologic consequences. Discovered a relatively high prevalence of potentially harmful recessive alleles. However, whilst the identified STEAP3 mutations exhibited impaired ferrireductase activity in vitro, they had little or no effect on erythrocyte phenotypes
Intellectual disability syndromic and non-syndromic v1.662 TTBK1 Zornitza Stark Marked gene: TTBK1 as ready
Intellectual disability syndromic and non-syndromic v1.662 TTBK1 Zornitza Stark Gene: ttbk1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.662 Zornitza Stark Copied gene TTBK1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.662 TTBK1 Zornitza Stark gene: TTBK1 was added
gene: TTBK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TTBK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTBK1 were set to 41545183
Phenotypes for gene: TTBK1 were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v1.4286 TTBK1 Zornitza Stark Marked gene: TTBK1 as ready
Mendeliome v1.4286 TTBK1 Zornitza Stark Gene: ttbk1 has been classified as Red List (Low Evidence).
Mendeliome v1.4286 TTBK1 Zornitza Stark gene: TTBK1 was added
gene: TTBK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTBK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTBK1 were set to 41545183
Phenotypes for gene: TTBK1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: TTBK1 was set to RED
Added comment: PMID 41545183 reports 2 individuals from a single family with biallelic loss-of-function frameshift variant (p.Thr634ArgfsTer39) presenting with a severe syndromic neurodevelopmental disorder characterized by global developmental delay, microcephaly, progressive spasticity, non‑ambulatory status, and seizures in the older sibling. No functional studies were performed.
Sources: Literature
Mendeliome v1.4285 Zornitza Stark Copied gene C12orf40 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.4285 C12orf40 Zornitza Stark gene: C12orf40 was added
gene: C12orf40 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: C12orf40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf40 were set to 41580510; 37612290; 37604834
Phenotypes for gene: C12orf40 were set to Infertility disorder, MONDO:0005047, C12orf40-related
Infertility and Recurrent Pregnancy Loss v1.81 C12orf40 Zornitza Stark Classified gene: C12orf40 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.81 C12orf40 Zornitza Stark Gene: c12orf40 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.80 C12orf40 Zornitza Stark gene: C12orf40 was added
gene: C12orf40 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: C12orf40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C12orf40 were set to 41580510; 37612290; 37604834
Phenotypes for gene: C12orf40 were set to Infertility disorder, MONDO:0005047, C12orf40-related
Review for gene: C12orf40 was set to GREEN
Added comment: PMID 37604834, 37612290 and 41580510 report a total of 8 individuals from 6 unrelated families with biallelic loss-of-function C12ORF40 variants presenting with severe male infertility due to spermatogenic failure (non‑obstructive azoospermia or severe oligoasthenoteratozoospermia). Affected men have normal hormone levels but exhibit meiotic arrest or markedly increased sperm sex‑chromosome aneuploidy. Mouse knockout and knock‑in models recapitulate the infertility phenotype, and in vitro assays demonstrate loss of nucleic‑acid binding activity, supporting pathogenicity.
Sources: Literature
Cataract v0.626 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Cataract v0.626 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Amber List (Moderate Evidence).
Cataract v0.626 ZEB2 Zornitza Stark Classified gene: ZEB2 as Amber List (moderate evidence)
Cataract v0.626 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Amber List (Moderate Evidence).
Cataract v0.625 ZEB2 Zornitza Stark gene: ZEB2 was added
gene: ZEB2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ZEB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZEB2 were set to 36676725; 25899569
Phenotypes for gene: ZEB2 were set to Mowat-Wilson syndrome, MIM# 235730
Review for gene: ZEB2 was set to AMBER
Added comment: PMID 25899569 reports four unrelated families with heterozygous loss‑of‑function ZEB2 variants causing Mowat‑Wilson syndrome; one of these families had cataract. PMID 36676725 reports one unrelated family with a de novo nonsense ZEB2 variant presenting with bilateral developmental cataract as part of Mowat‑Wilson syndrome.
Sources: Literature
Cataract v0.624 VCAN Zornitza Stark Marked gene: VCAN as ready
Cataract v0.624 VCAN Zornitza Stark Gene: vcan has been classified as Amber List (Moderate Evidence).
Cataract v0.624 VCAN Zornitza Stark Classified gene: VCAN as Amber List (moderate evidence)
Cataract v0.624 VCAN Zornitza Stark Gene: vcan has been classified as Amber List (Moderate Evidence).
Cataract v0.623 VCAN Zornitza Stark gene: VCAN was added
gene: VCAN was added to Cataract. Sources: Literature
Mode of inheritance for gene: VCAN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: VCAN were set to 36333947; 29071374
Phenotypes for gene: VCAN were set to Wagner syndrome 1, MIM# 143200
Review for gene: VCAN was set to AMBER
Added comment: PMID 29071374 reports 28 individuals from 1 family with heterozygous splice‑acceptor c.4004-1G>A variant presenting with Wagner syndrome (vitreoretinopathy, cataract, retinal detachment). PMID 36333947 reports 4 individuals from 1 family with heterozygous splice‑site indel c.4004-4_c.4004-3delinsCA variant presenting with Wagner vitreoretinopathy (cataract, vitreous syneresis, retinal detachment).
Sources: Literature
Fetal anomalies v1.527 DHRS3 Zornitza Stark Phenotypes for gene: DHRS3 were changed from Syndromic disease, MONDO:0002254, DHRS3-related to Craniosynostosis-scoliosis syndrome, MIM# 621499
Fetal anomalies v1.526 DHRS3 Zornitza Stark edited their review of gene: DHRS3: Changed phenotypes: Craniosynostosis-scoliosis syndrome, MIM# 621499
Mendeliome v1.4284 DHRS3 Zornitza Stark Phenotypes for gene: DHRS3 were changed from Syndromic disease, MONDO:0002254, DHRS3-related to Craniosynostosis-scoliosis syndrome, MIM# 621499
Mendeliome v1.4283 DHRS3 Zornitza Stark edited their review of gene: DHRS3: Changed phenotypes: Craniosynostosis-scoliosis syndrome, MIM# 621499
Craniosynostosis v1.75 DHRS3 Zornitza Stark Phenotypes for gene: DHRS3 were changed from Syndromic disease, MONDO:0002254, DHRS3-related to Craniosynostosis-scoliosis syndrome, MIM# 621499
Craniosynostosis v1.74 DHRS3 Zornitza Stark edited their review of gene: DHRS3: Changed phenotypes: Craniosynostosis-scoliosis syndrome, MIM# 621499
Congenital Heart Defect v0.524 DHRS3 Zornitza Stark Phenotypes for gene: DHRS3 were changed from Syndromic disease, MONDO:0002254, DHRS3-related to Craniosynostosis-scoliosis syndrome, MIM# 621499
Congenital Heart Defect v0.523 DHRS3 Zornitza Stark edited their review of gene: DHRS3: Changed phenotypes: Craniosynostosis-scoliosis syndrome, MIM# 621499
Intellectual disability syndromic and non-syndromic v1.661 TMEM189 Chirag Patel Marked gene: TMEM189 as ready
Intellectual disability syndromic and non-syndromic v1.661 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.411 TMEM189 Chirag Patel Marked gene: TMEM189 as ready
Microcephaly v1.411 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.411 Chirag Patel Copied gene TMEM189 from panel Mendeliome
Microcephaly v1.411 TMEM189 Chirag Patel gene: TMEM189 was added
gene: TMEM189 was added to Microcephaly. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TMEM189 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM189 were set to 41491239
Phenotypes for gene: TMEM189 were set to Neurodevelopmental disorder, MONDO:0700092, PEDS1-related
Intellectual disability syndromic and non-syndromic v1.661 Chirag Patel Copied gene TMEM189 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.661 TMEM189 Chirag Patel gene: TMEM189 was added
gene: TMEM189 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TMEM189 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM189 were set to 41491239
Phenotypes for gene: TMEM189 were set to Neurodevelopmental disorder, MONDO:0700092, PEDS1-related
Mendeliome v1.4283 TMEM189 Chirag Patel Marked gene: TMEM189 as ready
Mendeliome v1.4283 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4283 TMEM189 Chirag Patel Classified gene: TMEM189 as Amber List (moderate evidence)
Mendeliome v1.4283 TMEM189 Chirag Patel Gene: tmem189 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4282 TMEM189 Chirag Patel gene: TMEM189 was added
gene: TMEM189 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM189 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM189 were set to 41491239
Phenotypes for gene: TMEM189 were set to Neurodevelopmental disorder, MONDO:0700092, PEDS1-related
Review for gene: TMEM189 was set to AMBER
Added comment: 2 individuals from 2 unrelated consanguineous families presenting with microcephaly, global developmental delay, growth retardation, dysmorphic facial features and congenital cataracts (in one case). Both individuals had the same rare homozygous frameshift variant (c.104delC, p.Ala35Valfs*16) in PEDS1 gene (aka TMEM189). The variant segregated in the family. PEDS1 encodes the plasmanylethanolamine desaturase that catalyzes the final step of plasmalogen biosynthesis. Functional studies show the mutant protein is unstable and undetectable in COS7 cells, and mouse Peds1‑/‑ knockouts display microcephaly and neuroanatomical defects mirroring the human phenotype. Rescue of neuronal migration deficits by RNAi‑resistant wild‑type PEDS1 confirms loss‑of‑function as the disease mechanism.
Sources: Literature
Incidentalome v0.421 Bryony Thompson Copied gene DLST from panel Paraganglioma_phaeochromocytoma
Incidentalome v0.421 DLST Bryony Thompson gene: DLST was added
gene: DLST was added to Incidentalome. Sources: Expert Review Red,Literature,Expert Review,Expert list
Mode of inheritance for gene: DLST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLST were set to PMID: 30929736, 33180916
Phenotypes for gene: DLST were set to Paragangliomas 7, MONDO:0032771; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 7, MIM#618475
Cataract v0.622 TENM3 Zornitza Stark Marked gene: TENM3 as ready
Cataract v0.622 TENM3 Zornitza Stark Gene: tenm3 has been classified as Amber List (Moderate Evidence).
Cataract v0.622 TENM3 Zornitza Stark Classified gene: TENM3 as Amber List (moderate evidence)
Cataract v0.622 TENM3 Zornitza Stark Gene: tenm3 has been classified as Amber List (Moderate Evidence).
Cataract v0.621 TENM3 Zornitza Stark gene: TENM3 was added
gene: TENM3 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TENM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TENM3 were set to 36911040; 32799327
Phenotypes for gene: TENM3 were set to Microphthalmia, syndromic 15, MIM# 615145
Review for gene: TENM3 was set to AMBER
Added comment: PMID 32799327 reports a family with a homozygous nonsense TENM3 variant causing congenital cataract, microphthalmia and coloboma. PMID 36911040 reports 2 unrelated families with biallelic TENM3 variants; family 1 has congenital cataract, microphthalmia, microcephaly and developmental delay, family 2 has esotropia with speech and motor delay.
Sources: Literature
Cataract v0.620 SIX6 Zornitza Stark Marked gene: SIX6 as ready
Cataract v0.620 SIX6 Zornitza Stark Gene: six6 has been classified as Amber List (Moderate Evidence).
Cataract v0.620 SIX6 Zornitza Stark Classified gene: SIX6 as Amber List (moderate evidence)
Cataract v0.620 SIX6 Zornitza Stark Gene: six6 has been classified as Amber List (Moderate Evidence).
Cataract v0.619 SIX6 Zornitza Stark gene: SIX6 was added
gene: SIX6 was added to Cataract. Sources: Literature
Mode of inheritance for gene: SIX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIX6 were set to 35693420
Phenotypes for gene: SIX6 were set to Optic disc anomalies with retinal and/or macular dystrophy, MIM# 212550
Review for gene: SIX6 was set to AMBER
Added comment: PMID 35693420 reports four individuals from two unrelated consanguineous families with biallelic SIX6 variants (c.547G>C p.Asp183His missense; c.-227_572+235del1034 exon‑1 deletion) presenting with congenital cataract, microcornea, corneal opacification and variable iris coloboma or microphthalmia. The variants segregate with disease, are absent from population databases, and in silico structural modelling predicts loss‑of‑function.
Sources: Literature
Cataract v0.618 MFRP Zornitza Stark Marked gene: MFRP as ready
Cataract v0.618 MFRP Zornitza Stark Gene: mfrp has been classified as Amber List (Moderate Evidence).
Cataract v0.618 MFRP Zornitza Stark Classified gene: MFRP as Amber List (moderate evidence)
Cataract v0.618 MFRP Zornitza Stark Gene: mfrp has been classified as Amber List (Moderate Evidence).
Cataract v0.617 MFRP Zornitza Stark gene: MFRP was added
gene: MFRP was added to Cataract. Sources: Literature
Mode of inheritance for gene: MFRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFRP were set to 36605040
Phenotypes for gene: MFRP were set to Microphthalmia, isolated 5, MIM# 611040
Review for gene: MFRP was set to AMBER
Added comment: PMID 36605040 reports 2 individuals from 2 unrelated families with biallelic canonical splice-site MFRP variants presenting with nanophthalmos, high hyperopia, retinitis pigmentosa, and early-onset cataract (nuclear sclerotic).
Sources: Literature
Cataract v0.616 MAFA Zornitza Stark Marked gene: MAFA as ready
Cataract v0.616 MAFA Zornitza Stark Gene: mafa has been classified as Amber List (Moderate Evidence).
Cataract v0.616 MAFA Zornitza Stark Classified gene: MAFA as Amber List (moderate evidence)
Cataract v0.616 MAFA Zornitza Stark Gene: mafa has been classified as Amber List (Moderate Evidence).
Cataract v0.615 MAFA Zornitza Stark gene: MAFA was added
gene: MAFA was added to Cataract. Sources: Literature
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAFA were set to 29339498
Phenotypes for gene: MAFA were set to Insulinomatosis and diabetes mellitus, MIM# 147630
Review for gene: MAFA was set to AMBER
Added comment: PMID 29339498 reports a heterozygous MAFA p.Ser64Phe gain‑of‑function missense variant in two unrelated families with autosomal dominant insulinomatosis/diabetes and in the index family four individuals with congenital cataract (±glaucoma).
Sources: Literature
Mendeliome v1.4281 LRPAP1 Bryony Thompson Marked gene: LRPAP1 as ready
Mendeliome v1.4281 LRPAP1 Bryony Thompson Gene: lrpap1 has been classified as Green List (High Evidence).
Mendeliome v1.4281 LRPAP1 Bryony Thompson Classified gene: LRPAP1 as Green List (high evidence)
Mendeliome v1.4281 LRPAP1 Bryony Thompson Gene: lrpap1 has been classified as Green List (High Evidence).
Mendeliome v1.4280 LRPAP1 Bryony Thompson gene: LRPAP1 was added
gene: LRPAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRPAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRPAP1 were set to 23830514; 25525168; 36261846; 39444998
Phenotypes for gene: LRPAP1 were set to myopia 23, autosomal recessive MONDO:0014183
Review for gene: LRPAP1 was set to GREEN
Added comment: At least 4 families reported with homozygous variants, and a supporting zebrafish model
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.79 Bryony Thompson Copied gene ACR from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.79 ACR Bryony Thompson gene: ACR was added
gene: ACR was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACR were set to 37004249
Phenotypes for gene: ACR were set to spermatogenic failure MONDO:0004983
Mendeliome v1.4279 ACR Bryony Thompson Marked gene: ACR as ready
Mendeliome v1.4279 ACR Bryony Thompson Gene: acr has been classified as Red List (Low Evidence).
Mendeliome v1.4279 ACR Bryony Thompson gene: ACR was added
gene: ACR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACR were set to 37004249
Phenotypes for gene: ACR were set to spermatogenic failure MONDO:0004983
Review for gene: ACR was set to RED
Added comment: A single consanguineous family reported with a homozygous stopgain variant (c.167G>A, p.Trp56*) and supporting in vitro assay.
Sources: Literature
Differences of Sex Development v1.39 Sarah Milton Copied Region ISCA-46303-Loss from panel Common deletion and duplication syndromes
Differences of Sex Development v1.39 ISCA-46303-Loss Sarah Milton Region: ISCA-46303-Loss was added
Region: ISCA-46303-Loss was added to Differences of Sex Development. Sources: ClinGen
Mode of inheritance for Region: ISCA-46303-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: ISCA-46303-Loss were set to PMID: 24934569, 26663529, 19234473, 26152199, 30552336
Cataract v0.614 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Cataract v0.614 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Cataract v0.614 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Cataract v0.614 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Cataract v0.613 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JAG1 were set to 40257159; 37337769; 32883240
Phenotypes for gene: JAG1 were set to Alagille syndrome 1, MIM# 118450
Review for gene: JAG1 was set to GREEN
Added comment: Cataract is a recognised feature of the condition.
Sources: Literature
Cataract v0.612 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Cataract v0.612 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Amber List (Moderate Evidence).
Cataract v0.612 DYNC1H1 Zornitza Stark Classified gene: DYNC1H1 as Amber List (moderate evidence)
Cataract v0.612 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Amber List (Moderate Evidence).
Cataract v0.611 DYNC1H1 Zornitza Stark gene: DYNC1H1 was added
gene: DYNC1H1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DYNC1H1 were set to 27754416; 27331017
Phenotypes for gene: DYNC1H1 were set to Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Review for gene: DYNC1H1 was set to AMBER
Added comment: PMID 27331017 reports 1 individual with a de novo heterozygous missense DYNC1H1 variant (p.G3658E) presenting with severe malformation of cortical development and bilateral congenital cataract. PMID 27754416 reports a second individual with a de novo heterozygous missense DYNC1H1 variant (p.R2332C) presenting with congenital cataracts, polymicrogyria, developmental delay, gut dysmotility and sensory neuropathy.
Sources: Literature
Cataract v0.610 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Cataract v0.610 CWC27 Zornitza Stark Gene: cwc27 has been classified as Amber List (Moderate Evidence).
Cataract v0.610 CWC27 Zornitza Stark Classified gene: CWC27 as Amber List (moderate evidence)
Cataract v0.610 CWC27 Zornitza Stark Gene: cwc27 has been classified as Amber List (Moderate Evidence).
Cataract v0.609 CWC27 Zornitza Stark gene: CWC27 was added
gene: CWC27 was added to Cataract. Sources: Literature
Mode of inheritance for gene: CWC27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWC27 were set to 38840272; 31481716
Phenotypes for gene: CWC27 were set to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Review for gene: CWC27 was set to AMBER
Added comment: PMIDs 31481716 and 38840272 report 2 individuals from 2 unrelated families with biallelic loss-of-function CWC27 variants presenting with congenital cataract (often accompanied by retinal dystrophy, skeletal anomalies, short stature, intellectual disability, and hypergonadotropic hypogonadism).
Sources: Literature
Cataract v0.608 ARCN1 Zornitza Stark Marked gene: ARCN1 as ready
Cataract v0.608 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Amber List (Moderate Evidence).
Cataract v0.608 ARCN1 Zornitza Stark Classified gene: ARCN1 as Amber List (moderate evidence)
Cataract v0.608 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Amber List (Moderate Evidence).
Cataract v0.607 ARCN1 Zornitza Stark gene: ARCN1 was added
gene: ARCN1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ARCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARCN1 were set to 35300924
Phenotypes for gene: ARCN1 were set to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Review for gene: ARCN1 was set to AMBER
Added comment: PMID 35300924 reports 4 individuals from 2 unrelated families with biallelic loss-of-function ARCN1 variants presenting with cataract (onset infancy to early adolescence) as part of ARCN1‑related syndrome.
Sources: Literature
Regression v0.604 ZBTB11 Zornitza Stark Marked gene: ZBTB11 as ready
Regression v0.604 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Regression v0.604 ZBTB11 Zornitza Stark Publications for gene: ZBTB11 were set to 29893856
Regression v0.603 ZBTB11 Zornitza Stark changed review comment from: 2 consanguineous families in which several members had impaired intellectual development. 2 different homozygous missense mutations in the ZBTB11 gene. In vitro functional expression studies in HEK293 cells showed that the mutant proteins were excluded from the nucleolus, where the wildtype protein is predominantly localized.; to: 2 consanguineous families in which several members had impaired intellectual development. 2 different homozygous missense mutations in the ZBTB11 gene. In vitro functional expression studies in HEK293 cells showed that the mutant proteins were excluded from the nucleolus, where the wildtype protein is predominantly localized.

Regression is part of the phenotype.
Regression v0.603 Zornitza Stark Copied gene ZBTB11 from panel Mendeliome
Regression v0.603 ZBTB11 Zornitza Stark gene: ZBTB11 was added
gene: ZBTB11 was added to Regression. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ZBTB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB11 were set to 29893856
Phenotypes for gene: ZBTB11 were set to Intellectual developmental disorder, autosomal recessive 69, OMIM #618383
Cataract v0.606 ZBTB11 Zornitza Stark Marked gene: ZBTB11 as ready
Cataract v0.606 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Cataract v0.606 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Green List (high evidence)
Cataract v0.606 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Cataract v0.605 ZBTB11 Zornitza Stark gene: ZBTB11 was added
gene: ZBTB11 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ZBTB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB11 were set to 38899514
Phenotypes for gene: ZBTB11 were set to Intellectual developmental disorder, autosomal recessive 69, MIM# 618383
Review for gene: ZBTB11 was set to GREEN
Added comment: PMID 38899514 reports 29 individuals from 17 unrelated families with biallelic ZBTB11 variants. All affected have neurodevelopmental delay/intellectual disability; 10 patients present with bilateral cataracts.
Sources: Literature
Cataract v0.604 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Cataract v0.604 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Cataract v0.604 VPS13B Zornitza Stark Classified gene: VPS13B as Green List (high evidence)
Cataract v0.604 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Cataract v0.603 VPS13B Zornitza Stark Classified gene: VPS13B as Green List (high evidence)
Cataract v0.603 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Cataract v0.602 VPS13B Zornitza Stark gene: VPS13B was added
gene: VPS13B was added to Cataract. Sources: Literature
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13B were set to 40813981; 37901634; 32915983
Phenotypes for gene: VPS13B were set to Cohen syndrome, MIM# 216550
Review for gene: VPS13B was set to GREEN
Added comment: PMID 32915983 reports two adult siblings with Cohen syndrome and bilateral nuclear‑sclerotic cataracts; PMID 37901634 reports a 39‑year‑old male with Cohen syndrome, early adult‑onset cataract and two novel VPS13B variants (c.5138T>C missense, c.10179del frameshift); PMID 40813981 reports a 24‑year‑old male with Cohen syndrome, bilateral cataract, spherical lenses, lens subluxation and retinitis pigmentosa carrying a homozygous splice‑site VPS13B variant (c.6865+1G>T). Functional mouse knockout models (Vps13bΔEx3/ΔEx3) develop early‑onset hypermature cataracts, supporting a causal link.
Sources: Literature
Cataract v0.601 USP9X Zornitza Stark Marked gene: USP9X as ready
Cataract v0.601 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Cataract v0.601 USP9X Zornitza Stark Classified gene: USP9X as Green List (high evidence)
Cataract v0.601 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Cataract v0.600 USP9X Zornitza Stark gene: USP9X was added
gene: USP9X was added to Cataract. Sources: Literature
Mode of inheritance for gene: USP9X 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: USP9X were set to 38099911; 37895297
Phenotypes for gene: USP9X were set to Intellectual developmental disorder, X-linked 99, syndromic, female-restricted, MIM# 300968
Review for gene: USP9X was set to GREEN
Added comment: PMID 37895297 reports three unrelated female families with heterozygous loss‑of‑function USP9X variants (splice c.1314+2T>C, nonsense c.121G>T, frameshift c.1603dupA) presenting with Axenfeld–Rieger anomaly, congenital glaucoma, corneal neovascularization and cataract (two cases). PMID 38099911 reports an additional unrelated family with a heterozygous USP9X c.799_802del deletion causing bilateral cataracts, posterior lentiglobus and multiple systemic anomalies.
Sources: Literature
Mendeliome v1.4278 FGF10 Bryony Thompson Deleted their comment
Mendeliome v1.4278 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v1.6 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v1.6 FGF10 Bryony Thompson Deleted their comment
Pulmonary Fibrosis_Interstitial Lung Disease v1.6 FGF10 Bryony Thompson changed review comment from: Amber for biallelic - 2 families with a lethal congenital alveolar dysplasia phenotype with compound heterozygous coding‑loss‑of‑function with non-coding SNVs in a predicted lung-specific enhancer region.; to: Amber for biallelic - 2 families with a lethal congenital alveolar dysplasia phenotype with compound heterozygous coding‑loss‑of‑function with non-coding SNVs in a predicted lung-specific enhancer region.
Cataract v0.599 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
Cataract v0.599 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Cataract v0.599 TRNT1 Zornitza Stark Classified gene: TRNT1 as Green List (high evidence)
Cataract v0.599 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Cataract v0.598 TRNT1 Zornitza Stark gene: TRNT1 was added
gene: TRNT1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRNT1 were set to 36937953; 34864912; 27389523
Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084
Review for gene: TRNT1 was set to GREEN
Added comment: PMID 27389523 reports three affected siblings from one family with childhood cataract, inner retinal dysfunction, immunodeficiency and a homozygous missense TRNT1 p.Arg99Trp variant. PMID 34864912 describes a 49‑year‑old male with congenital cataract, recurrent infections, B‑cell immunodeficiency, periodic fevers and hypergonadotropic hypogonadism carrying the same homozygous p.Arg99Trp variant. PMID 36937953 presents three unrelated patients from two families with sideroblastic anemia, B‑cell immunodeficiency, periodic fevers, developmental delay and bilateral cataracts caused by compound heterozygous TRNT1 variants (c.1246A>G/p.K416E, c.1056+1G>A, c.574C>T/p.Q192*, c.464T>C/p.I155T). Across the three papers there are seven patients from four unrelated families with biallelic loss‑of‑function TRNT1 variants and a consistent phenotype that includes cataract.
Sources: Literature
Cataract v0.597 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Cataract v0.597 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Cataract v0.597 TRAPPC11 Zornitza Stark Classified gene: TRAPPC11 as Green List (high evidence)
Cataract v0.597 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Cataract v0.596 TRAPPC11 Zornitza Stark gene: TRAPPC11 was added
gene: TRAPPC11 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC11 were set to 34648194; 26322222
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356
Review for gene: TRAPPC11 was set to GREEN
Added comment: PMID 26322222 and PMID 34648194 together describe five individuals from five unrelated families with biallelic loss‑of‑function TRAPPC11 variants. The affected individuals present with congenital/early‑onset muscular dystrophy, infantile‑onset cataract, markedly elevated CK, and multisystem involvement (fatty liver in one family and severe α‑dystroglycan hypoglycosylation in muscle).
Sources: Literature
Cataract v0.595 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Cataract v0.595 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Cataract v0.595 TOR1AIP1 Zornitza Stark Classified gene: TOR1AIP1 as Green List (high evidence)
Cataract v0.595 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Cataract v0.594 TOR1AIP1 Zornitza Stark gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 32055997; 30723199
Phenotypes for gene: TOR1AIP1 were set to Syndromic disease, MONDO:0002254, TOR1AIP1-related
Review for gene: TOR1AIP1 was set to GREEN
Added comment: PMID 30723199 reports 7 individuals from 5 unrelated families with biallelic nonsense TOR1AIP1 (c.961C>T) variants presenting with congenital bilateral cataract, severe neurodevelopmental impairment, intra‑uterine growth retardation, microcephaly, sensorineural deafness and cardiac defects. PMID 32055997 adds 2 unrelated individuals from 2 families carrying compound‑heterozygous loss‑of‑function TOR1AIP1 variants (frameshift + missense or nonsense + frameshift) with a closely overlapping multisystemic phenotype that also includes cataract, hearing loss, cardiac disease and muscular atrophy.

Note gene has been associated with multiple phenotypes, predominantly muscle-related; described as 'envelopathy' in some papers.
Sources: Literature
Cataract v0.593 TONSL Zornitza Stark Marked gene: TONSL as ready
Cataract v0.593 TONSL Zornitza Stark Gene: tonsl has been classified as Green List (High Evidence).
Cataract v0.593 TONSL Zornitza Stark Classified gene: TONSL as Green List (high evidence)
Cataract v0.593 TONSL Zornitza Stark Gene: tonsl has been classified as Green List (High Evidence).
Cataract v0.592 TONSL Zornitza Stark gene: TONSL was added
gene: TONSL was added to Cataract. Sources: Literature
Mode of inheritance for gene: TONSL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TONSL were set to 30773277
Phenotypes for gene: TONSL were set to Spondyloepimetaphyseal dysplasia, sponastrime type, MIM# 271510
Review for gene: TONSL was set to GREEN
Added comment: PMID 30773277 reports 9 individuals from 8 unrelated families with bi‑allelic TONSL variants causing Sponastrime dysplasia, a skeletal dysplasia characterised by disproportionate short stature, platyspondyly, metaphyseal striations and, in three families, childhood bilateral cataracts.
Sources: Literature
Cataract v0.591 TKT Zornitza Stark Marked gene: TKT as ready
Cataract v0.591 TKT Zornitza Stark Gene: tkt has been classified as Green List (High Evidence).
Cataract v0.591 TKT Zornitza Stark Classified gene: TKT as Green List (high evidence)
Cataract v0.591 TKT Zornitza Stark Gene: tkt has been classified as Green List (High Evidence).
Cataract v0.590 TKT Zornitza Stark gene: TKT was added
gene: TKT was added to Cataract. Sources: Literature
Mode of inheritance for gene: TKT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKT were set to 27259054
Phenotypes for gene: TKT were set to Short stature, developmental delay, and congenital heart defects, MIM# 617044
Review for gene: TKT was set to GREEN
Added comment: Cataracts are reported as part of this condition.
Sources: Literature
Cataract v0.589 TELO2 Zornitza Stark Marked gene: TELO2 as ready
Cataract v0.589 TELO2 Zornitza Stark Gene: telo2 has been classified as Green List (High Evidence).
Cataract v0.589 TELO2 Zornitza Stark Classified gene: TELO2 as Green List (high evidence)
Cataract v0.589 TELO2 Zornitza Stark Gene: telo2 has been classified as Green List (High Evidence).
Cataract v0.588 TELO2 Zornitza Stark gene: TELO2 was added
gene: TELO2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TELO2 were set to 37215500; 36797513; 28944240
Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, MIM# 616954
Review for gene: TELO2 was set to GREEN
Added comment: Multiple individuals reported with cataract as part of the phenotype.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v1.6 FGF10 Bryony Thompson edited their review of gene: FGF10: Changed mode of inheritance: Other
Mendeliome v1.4278 SLC7A8 Zornitza Stark Marked gene: SLC7A8 as ready
Mendeliome v1.4278 SLC7A8 Zornitza Stark Gene: slc7a8 has been classified as Red List (Low Evidence).
Mendeliome v1.4278 Zornitza Stark Copied gene SLC7A8 from panel Cataract
Mendeliome v1.4278 SLC7A8 Zornitza Stark gene: SLC7A8 was added
gene: SLC7A8 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SLC7A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A8 were set to 40229141; 31231240
Phenotypes for gene: SLC7A8 were set to Cataract, MONDO:0005129, SLC7A8-related
Cataract v0.587 SLC7A8 Zornitza Stark Marked gene: SLC7A8 as ready
Cataract v0.587 SLC7A8 Zornitza Stark Gene: slc7a8 has been classified as Red List (Low Evidence).
Cataract v0.587 SLC7A8 Zornitza Stark gene: SLC7A8 was added
gene: SLC7A8 was added to Cataract. Sources: Literature
Mode of inheritance for gene: SLC7A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A8 were set to 40229141; 31231240
Phenotypes for gene: SLC7A8 were set to Cataract, MONDO:0005129, SLC7A8-related
Review for gene: SLC7A8 was set to RED
Added comment: PMID 31231240 reports 2 affected siblings with autosomal recessive congenital bilateral sutural and zonular cataract caused by a homozygous frameshift c.1305del (p.Phe436Serfs*22) that abolishes LAT2 transport activity in HeLa cells. PMID 40229141 reports a single child from an unrelated family with compound heterozygous SLC7A8 variants (c.1017-1G>T splice-site and c.289G>A missense) and cataract; a minigene assay shows exon skipping for the splice variant. No other functional data, one of the variants is homozygous, hence RED rating.
Sources: Literature
Cataract v0.586 SEC23A Zornitza Stark Marked gene: SEC23A as ready
Cataract v0.586 SEC23A Zornitza Stark Gene: sec23a has been classified as Green List (High Evidence).
Cataract v0.586 SEC23A Zornitza Stark Classified gene: SEC23A as Green List (high evidence)
Cataract v0.586 SEC23A Zornitza Stark Gene: sec23a has been classified as Green List (High Evidence).
Cataract v0.585 SEC23A Zornitza Stark gene: SEC23A was added
gene: SEC23A was added to Cataract. Sources: Literature
Mode of inheritance for gene: SEC23A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SEC23A were set to 38275611; 37828500; 34580982
Phenotypes for gene: SEC23A were set to Craniolenticulosutural dysplasia, MIM# 607812
Review for gene: SEC23A was set to GREEN
Added comment: Cataracts are reported in individuals with both dominant and recessive disease, but appear more common in recessive disease.
Sources: Literature
Mendeliome v1.4277 RRAGA Zornitza Stark Marked gene: RRAGA as ready
Mendeliome v1.4277 RRAGA Zornitza Stark Gene: rraga has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4277 Zornitza Stark Copied gene RRAGA from panel Cataract
Mendeliome v1.4277 RRAGA Zornitza Stark gene: RRAGA was added
gene: RRAGA was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RRAGA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RRAGA were set to 27294265
Phenotypes for gene: RRAGA were set to Cataract, MONDO:0005129, RRAGA-related
Cataract v0.584 RRAGA Zornitza Stark Marked gene: RRAGA as ready
Cataract v0.584 RRAGA Zornitza Stark Gene: rraga has been classified as Amber List (Moderate Evidence).
Cataract v0.584 RRAGA Zornitza Stark Classified gene: RRAGA as Amber List (moderate evidence)
Cataract v0.584 RRAGA Zornitza Stark Gene: rraga has been classified as Amber List (Moderate Evidence).
Cataract v0.583 RRAGA Zornitza Stark gene: RRAGA was added
gene: RRAGA was added to Cataract. Sources: Literature
Mode of inheritance for gene: RRAGA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RRAGA were set to 27294265
Phenotypes for gene: RRAGA were set to Cataract, MONDO:0005129, RRAGA-related
Review for gene: RRAGA was set to AMBER
Added comment: PMID 27294265 reports 11 individuals from 3 unrelated families with heterozygous RRAGA variants presenting with autosomal dominant cataracts (juvenile-onset progressive posterior subcapsular cataract in 10 patients from 2 families; congenital nuclear cataract in 1 patient). The missense p.Leu60Arg co‑segregates with disease (LOD 2.975) and activates mTORC1 signalling in lens epithelial cells; the 5′‑UTR c.-16G>A reduces promoter activity (~80%). The missense variant is present in one of the multiplex families and in an independent individual -- appears that the two families are not related and these are independent events.

Nevertheless, two variants only and no direct functional work to link to cataract pathogenesis, hence Amber rating.
Sources: Literature
Cataract v0.582 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Cataract v0.582 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Cataract v0.582 RECQL4 Zornitza Stark Classified gene: RECQL4 as Green List (high evidence)
Cataract v0.582 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Cataract v0.581 RECQL4 Zornitza Stark gene: RECQL4 was added
gene: RECQL4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to 40485636; 37228773; 36164748; 33294214
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome, type 2, MIM# 268400
Review for gene: RECQL4 was set to GREEN
Added comment: Cataract is a feature of RTS.
Sources: Literature