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Differences of Sex Development v0.166 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to
Differences of Sex Development v0.165 NR0B1 Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.163 NR0B1 Zornitza Stark Tag SV/CNV tag was added to gene: NR0B1.
Differences of Sex Development v0.163 NR0B1 Zornitza Stark reviewed gene: NR0B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 7951319; Phenotypes: 46XY sex reversal 2, dosage-sensitive, MIM# 300018; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Marked gene: HOXA13 as ready
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Gene: hoxa13 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Phenotypes for gene: PROKR2 were changed from to Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200
Differences of Sex Development v0.160 PROKR2 Zornitza Stark Publications for gene: PROKR2 were set to
Differences of Sex Development v0.159 PROKR2 Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3412 NSMF Zornitza Stark Marked gene: NSMF as ready
Mendeliome v0.3412 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3412 NSMF Zornitza Stark Phenotypes for gene: NSMF were changed from to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Mendeliome v0.3411 NSMF Zornitza Stark Publications for gene: NSMF were set to
Mendeliome v0.3410 NSMF Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3409 NSMF Zornitza Stark Classified gene: NSMF as Red List (low evidence)
Mendeliome v0.3409 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Mendeliome v0.3408 NSMF Zornitza Stark reviewed gene: NSMF: Rating: RED; Mode of pathogenicity: None; Publications: 15362570, 17235395, 21700882; Phenotypes: Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.172 NSMF Zornitza Stark Marked gene: NSMF as ready
Callosome v0.172 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Callosome v0.172 NSMF Zornitza Stark Phenotypes for gene: NSMF were changed from to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Callosome v0.171 NSMF Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.170 NSMF Zornitza Stark Classified gene: NSMF as Red List (low evidence)
Callosome v0.170 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Callosome v0.169 NSMF Zornitza Stark reviewed gene: NSMF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.157 NSMF Zornitza Stark Marked gene: NSMF as ready
Differences of Sex Development v0.157 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Differences of Sex Development v0.157 NSMF Zornitza Stark gene: NSMF was added
gene: NSMF was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NSMF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSMF were set to 15362570; 17235395; 21700882
Phenotypes for gene: NSMF were set to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Review for gene: NSMF was set to RED
Added comment: Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals).
Sources: Expert list
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Tag disputed tag was added to gene: SPRY4.
Mendeliome v0.3408 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Mendeliome v0.3408 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3408 SPRY4 Zornitza Stark Tag disputed tag was added to gene: SPRY4.
Mendeliome v0.3408 SPRY4 Zornitza Stark Phenotypes for gene: SPRY4 were changed from to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Mendeliome v0.3407 SPRY4 Zornitza Stark Publications for gene: SPRY4 were set to
Mendeliome v0.3406 SPRY4 Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3405 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Mendeliome v0.3405 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.169 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Callosome v0.169 SPRY4 Zornitza Stark Gene: spry4 has been classified as Red List (Low Evidence).
Callosome v0.169 SPRY4 Zornitza Stark Phenotypes for gene: SPRY4 were changed from to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Callosome v0.168 SPRY4 Zornitza Stark Publications for gene: SPRY4 were set to
Callosome v0.167 SPRY4 Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.166 SPRY4 Zornitza Stark Classified gene: SPRY4 as Red List (low evidence)
Callosome v0.166 SPRY4 Zornitza Stark Gene: spry4 has been classified as Red List (Low Evidence).
Callosome v0.165 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: RED; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.155 SPRY4 Zornitza Stark gene: SPRY4 was added
gene: SPRY4 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPRY4 were set to 23643382
Phenotypes for gene: SPRY4 were set to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Review for gene: SPRY4 was set to AMBER
Added comment: 14 unrelated individuals reported originally. Three of these had variants in other IHH genes. The p.Lys177Arg variant is present in 454 individuals in gnomad, p.Ser241Tyr is present in 1279 individuals including 6 homozygotes, p.Val304Ile is present in 457 individuals. These population frequencies cast doubt on the gene-disease relationship.
Sources: Expert list
Mendeliome v0.3404 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Mendeliome v0.3404 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3404 KISS1 Zornitza Stark Phenotypes for gene: KISS1 were changed from to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Mendeliome v0.3403 KISS1 Zornitza Stark Publications for gene: KISS1 were set to
Mendeliome v0.3402 KISS1 Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3401 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Mendeliome v0.3401 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.165 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Callosome v0.165 KISS1 Zornitza Stark Gene: kiss1 has been classified as Red List (Low Evidence).
Callosome v0.165 KISS1 Zornitza Stark Phenotypes for gene: KISS1 were changed from to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Callosome v0.164 KISS1 Zornitza Stark Publications for gene: KISS1 were set to
Callosome v0.163 KISS1 Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.162 KISS1 Zornitza Stark Classified gene: KISS1 as Red List (low evidence)
Callosome v0.162 KISS1 Zornitza Stark Gene: kiss1 has been classified as Red List (Low Evidence).
Callosome v0.161 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: RED; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.154 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.154 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.153 KISS1 Zornitza Stark gene: KISS1 was added
gene: KISS1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: KISS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KISS1 were set to 22335740; 25783047; 22766261; 17563351
Phenotypes for gene: KISS1 were set to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Review for gene: KISS1 was set to AMBER
Added comment: Reported in Turkish families, supportive mouse model, but no variants identified in other cohorts. Role of KISS1 receptor much more established.
Sources: Expert list
Differences of Sex Development v0.152 TACR3 Zornitza Stark Marked gene: TACR3 as ready
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.152 TACR3 Zornitza Stark Classified gene: TACR3 as Green List (high evidence)
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.151 TACR3 Zornitza Stark gene: TACR3 was added
gene: TACR3 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: TACR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACR3 were set to 20332248; 19079066
Phenotypes for gene: TACR3 were set to Hypogonadotropic hypogonadism 11 with or without anosmia, MIM# 614840
Review for gene: TACR3 was set to GREEN
Added comment: Multiple families reported.
Sources: Expert list
Mendeliome v0.3400 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Mendeliome v0.3400 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3400 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from to Cryptorchidism, MIM# 219050
Mendeliome v0.3399 INSL3 Zornitza Stark Publications for gene: INSL3 were set to
Mendeliome v0.3398 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3397 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Mendeliome v0.3397 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.150 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Differences of Sex Development v0.150 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.150 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from to Cryptorchidism, MIM# 219050
Differences of Sex Development v0.149 INSL3 Zornitza Stark Publications for gene: INSL3 were set to
Differences of Sex Development v0.148 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.147 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Differences of Sex Development v0.147 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.161 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Callosome v0.161 IL17RD Zornitza Stark Gene: il17rd has been classified as Red List (Low Evidence).
Callosome v0.161 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Callosome v0.160 IL17RD Zornitza Stark Classified gene: IL17RD as Red List (low evidence)
Callosome v0.160 IL17RD Zornitza Stark Gene: il17rd has been classified as Red List (Low Evidence).
Callosome v0.159 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: None
Mendeliome v0.3396 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Mendeliome v0.3396 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3396 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Mendeliome v0.3395 IL17RD Zornitza Stark Publications for gene: IL17RD were set to
Mendeliome v0.3394 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3393 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Mendeliome v0.3393 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3392 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.146 IL17RD Zornitza Stark Tag disputed tag was added to gene: IL17RD.
Differences of Sex Development v0.146 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Differences of Sex Development v0.146 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Differences of Sex Development v0.145 IL17RD Zornitza Stark Publications for gene: IL17RD were set to
Differences of Sex Development v0.144 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.143 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Differences of Sex Development v0.143 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.142 IL17RD Zornitza Stark edited their review of gene: IL17RD: Changed rating: AMBER
Differences of Sex Development v0.142 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to Perrault syndrome 1, MIM# 233400
Differences of Sex Development v0.141 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Differences of Sex Development v0.140 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.139 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24553428, 23181892; Phenotypes: Perrault syndrome 1, MIM# 233400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.159 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Callosome v0.159 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Callosome v0.159 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Callosome v0.158 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Callosome v0.157 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to Other
Callosome v0.156 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Callosome v0.156 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Callosome v0.155 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: Other
Mendeliome v0.3392 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Mendeliome v0.3391 HS6ST1 Zornitza Stark edited their review of gene: HS6ST1: Changed mode of inheritance: Other
Mendeliome v0.3391 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Mendeliome v0.3391 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3391 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Mendeliome v0.3390 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Mendeliome v0.3389 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3388 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Mendeliome v0.3388 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Mendeliome v0.3387 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Differences of Sex Development v0.138 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Differences of Sex Development v0.137 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to Other
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.135 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: Other
Differences of Sex Development v0.135 HOXA13 Zornitza Stark Phenotypes for gene: HOXA13 were changed from to Hand-foot-uterus syndrome, MIM# 140000
Differences of Sex Development v0.134 HOXA13 Zornitza Stark Publications for gene: HOXA13 were set to
Differences of Sex Development v0.133 HOXA13 Zornitza Stark Mode of inheritance for gene: HOXA13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HOXA13 Zornitza Stark reviewed gene: HOXA13: Rating: GREEN; Mode of pathogenicity: None; Publications: 10839976, 9020844; Phenotypes: Hand-foot-uterus syndrome, MIM# 140000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Differences of Sex Development v0.132 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.132 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to Pituitary hormone deficiency, combined, 5, MIM# 182230
Differences of Sex Development v0.131 HESX1 Zornitza Stark Mode of inheritance for gene: HESX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.130 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 5, MIM# 182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Callosome v0.155 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Callosome v0.155 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Red List (Low Evidence).
Callosome v0.155 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Callosome v0.154 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.153 GNRH1 Zornitza Stark Classified gene: GNRH1 as Red List (low evidence)
Callosome v0.153 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Red List (Low Evidence).
Callosome v0.152 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3387 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Mendeliome v0.3387 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Mendeliome v0.3387 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Mendeliome v0.3386 GNRH1 Zornitza Stark Publications for gene: GNRH1 were set to
Mendeliome v0.3385 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3384 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Differences of Sex Development v0.129 GNRH1 Zornitza Stark Publications for gene: GNRH1 were set to
Differences of Sex Development v0.128 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.127 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2776 ZNF462 Zornitza Stark Phenotypes for gene: ZNF462 were changed from Weiss-Kruszka syndrome; OMIM# 618619 to Weiss-Kruszka syndrome, OMIM# 618619
Intellectual disability syndromic and non-syndromic v0.2775 ZNF462 Zornitza Stark Publications for gene: ZNF462 were set to PubMed: 31361404; 28513610
Mendeliome v0.3384 KIF3B Zornitza Stark Phenotypes for gene: KIF3B were changed from hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly; Retinitis pigmentosa 89, MIM#618955
Mendeliome v0.3383 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly, Retinitis pigmentosa 89, MIM#618955
Ciliopathies v0.193 KIF3B Zornitza Stark Phenotypes for gene: KIF3B were changed from hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly; Retinitis pigmentosa 89, MIM#618955
Ciliopathies v0.192 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly, Retinitis pigmentosa 89, MIM#618955
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Marked gene: CUX2 as ready
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Gene: cux2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.756 CUX2 Zornitza Stark Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, MIM#618141
Genetic Epilepsy v0.755 CUX2 Zornitza Stark Publications for gene: CUX2 were set to
Genetic Epilepsy v0.754 CUX2 Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.753 CUX2 Zornitza Stark reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 2963073, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, MIM#618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3383 CUX2 Zornitza Stark Marked gene: CUX2 as ready
Mendeliome v0.3383 CUX2 Zornitza Stark Added comment: Comment when marking as ready: At least 10 individuals reported with same recurrent de novo missense variant.
Mendeliome v0.3383 CUX2 Zornitza Stark Gene: cux2 has been classified as Green List (High Evidence).
Mendeliome v0.3383 CUX2 Zornitza Stark Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, MIM#618141
Mendeliome v0.3382 CUX2 Zornitza Stark Publications for gene: CUX2 were set to
Mendeliome v0.3381 CUX2 Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.96 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, MIM# 608799
Congenital Disorders of Glycosylation v0.95 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Congenital Disorders of Glycosylation v0.94 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.93 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23856421, 16641202, 10642602, 10642597; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3380 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Mendeliome v0.3380 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Mendeliome v0.3380 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Mendeliome v0.3379 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Mendeliome v0.3378 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3377 CUX2 Elena Savva reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 2963073, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, 618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Periventricular Grey Matter Heterotopia v0.10 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3377 DPM1 Elena Savva reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23856421; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3377 GIPC1 Zornitza Stark Marked gene: GIPC1 as ready
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3377 GIPC1 Zornitza Stark Classified gene: GIPC1 as Amber List (moderate evidence)
Mendeliome v0.3377 GIPC1 Zornitza Stark Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3376 GIPC1 Zornitza Stark gene: GIPC1 was added
gene: GIPC1 was added to Mendeliome. Sources: Literature
5'UTR, STR tags were added to gene: GIPC1.
Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIPC1 were set to 32413282
Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940
Review for gene: GIPC1 was set to AMBER
Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays.
Sources: Literature
Mendeliome v0.3375 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Mendeliome v0.3375 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Mendeliome v0.3375 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from to Cornelia de Lange syndrome 3, MIM#610759
Mendeliome v0.3374 SMC3 Zornitza Stark Publications for gene: SMC3 were set to
Mendeliome v0.3373 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Intellectual disability syndromic and non-syndromic v0.2773 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Intellectual disability syndromic and non-syndromic v0.2772 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2771 DEAF1 Zornitza Stark reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30923367, 24726472, 26048982, 28940898, 26834045; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3372 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Mendeliome v0.3372 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Mendeliome v0.3372 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Mendeliome v0.3371 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Mendeliome v0.3370 DEAF1 Zornitza Stark Mode of pathogenicity for gene: DEAF1 was changed from to Other
Mendeliome v0.3369 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Classified gene: RIPK4 as Green List (high evidence)
Multiple pterygium syndrome_Fetal akinesia sequence v0.3 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v0.2 RIPK4 Zornitza Stark gene: RIPK4 was added
gene: RIPK4 was added to Multiple pterygium syndrome. Sources: Expert Review
Mode of inheritance for gene: RIPK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPK4 were set to 28940926; 22197489; 22197488
Phenotypes for gene: RIPK4 were set to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Review for gene: RIPK4 was set to GREEN
Added comment: At least three unrelated families reported.
Sources: Expert Review
Arthrogryposis v0.189 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Arthrogryposis v0.189 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Arthrogryposis v0.189 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Arthrogryposis v0.188 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to
Arthrogryposis v0.187 RIPK4 Zornitza Stark Mode of inheritance for gene: RIPK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.186 RIPK4 Zornitza Stark reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940926, 22197489, 22197488; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3368 SMC3 Elena Savva reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18996922, 25655089, 31334757; Phenotypes: ornelia de Lange syndrome 3, 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3368 DEAF1 Elena Savva reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30923367, PMID 24726472; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.753 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.140 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.139 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3368 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3367 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2771 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2770 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3367 CLCC1 Zornitza Stark Phenotypes for gene: CLCC1 were changed from Retinitis pigmentosa 32 to Retinitis pigmentosa 32, MIM# 609913
Retinitis pigmentosa v0.56 CLCC1 Zornitza Stark Phenotypes for gene: CLCC1 were changed from Retinitis pigmentosa 32 to Retinitis pigmentosa 32, MIM# 609913
Retinitis pigmentosa v0.55 CLCC1 Zornitza Stark reviewed gene: CLCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30157172; Phenotypes: Retinitis pigmentosa 32, MIM# 609913; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3366 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Mendeliome v0.3366 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Mendeliome v0.3366 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction
Mendeliome v0.3365 ABCC9 Zornitza Stark Publications for gene: ABCC9 were set to
Mendeliome v0.3364 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3363 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31575858, 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, mild ID, similar facies, myopathy, cerebral white matter hyperintensities, cardiac systolic dysfunction; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Disorders of Glycosylation v0.93 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Differences of Sex Development v0.127 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.3363 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Mendeliome v0.3363 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3363 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Mendeliome v0.3362 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to
Mendeliome v0.3361 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3360 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Mendeliome v0.3360 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Tag disputed tag was added to gene: TSPYL1.
Mendeliome v0.3359 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Differences of Sex Development v0.124 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to
Differences of Sex Development v0.123 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Red List (low evidence)
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Differences of Sex Development v0.121 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from to Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858
Differences of Sex Development v0.120 WDR11 Zornitza Stark Publications for gene: WDR11 were set to
Differences of Sex Development v0.119 WDR11 Zornitza Stark Mode of inheritance for gene: WDR11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.118 KISS1R Zornitza Stark Marked gene: KISS1R as ready
Differences of Sex Development v0.118 KISS1R Zornitza Stark Gene: kiss1r has been classified as Green List (High Evidence).
Differences of Sex Development v0.118 KISS1R Zornitza Stark Phenotypes for gene: KISS1R were changed from to Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837)
Differences of Sex Development v0.117 KISS1R Zornitza Stark Publications for gene: KISS1R were set to
Differences of Sex Development v0.116 KISS1R Zornitza Stark Mode of inheritance for gene: KISS1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.92 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v0.92 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3359 PIGM Zornitza Stark Marked gene: PIGM as ready
Mendeliome v0.3359 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3359 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to Glycosylphosphatidylinositol deficiency, MIM# 610293; portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Mendeliome v0.3358 PIGM Zornitza Stark Publications for gene: PIGM were set to
Mendeliome v0.3357 PIGM Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3356 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Mendeliome v0.3356 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3355 PIGM Zornitza Stark Tag founder tag was added to gene: PIGM.
Differences of Sex Development v0.115 LEP Zornitza Stark Marked gene: LEP as ready
Differences of Sex Development v0.115 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Marked gene: LEP as ready
Mendeliome v0.3355 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Mendeliome v0.3355 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Mendeliome v0.3354 LEP Zornitza Stark Publications for gene: LEP were set to
Mendeliome v0.3353 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from Obesity, morbid, due to leptin deficiency (MIM#614962) to Obesity, morbid, due to leptin deficiency (MIM#614962)
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Marked gene: ST3GAL3 as ready
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Differences of Sex Development v0.114 LEP Zornitza Stark Publications for gene: LEP were set to
Differences of Sex Development v0.113 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Gene: nus1 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.91 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Mental retardation, autosomal recessive 12 MIM# 611090
Congenital Disorders of Glycosylation v0.91 NUS1 Zornitza Stark Publications for gene: NUS1 were set to
Mendeliome v0.3352 LEPR Zornitza Stark Marked gene: LEPR as ready
Mendeliome v0.3352 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Mendeliome v0.3352 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Mendeliome v0.3351 LEPR Zornitza Stark Publications for gene: LEPR were set to
Mendeliome v0.3350 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.112 LEPR Zornitza Stark Marked gene: LEPR as ready
Differences of Sex Development v0.112 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Differences of Sex Development v0.112 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Differences of Sex Development v0.111 LEPR Zornitza Stark Publications for gene: LEPR were set to
Differences of Sex Development v0.110 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.109 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Differences of Sex Development v0.109 FGF17 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green/Amber: contribution may not be monogenic.
Differences of Sex Development v0.109 FGF17 Zornitza Stark Gene: fgf17 has been classified as Green List (High Evidence).
Differences of Sex Development v0.109 FGF17 Zornitza Stark Publications for gene: FGF17 were set to
Differences of Sex Development v0.108 FGF17 Zornitza Stark Mode of inheritance for gene: FGF17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 FGF17 Zornitza Stark reviewed gene: FGF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 31748124; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 LHB Zornitza Stark Marked gene: LHB as ready
Differences of Sex Development v0.107 LHB Zornitza Stark Gene: lhb has been classified as Green List (High Evidence).
Differences of Sex Development v0.107 LHB Zornitza Stark Phenotypes for gene: LHB were changed from to Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300)
Differences of Sex Development v0.106 LHB Zornitza Stark Publications for gene: LHB were set to
Differences of Sex Development v0.105 LHB Zornitza Stark Mode of inheritance for gene: LHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Marked gene: FEZF1 as ready
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Phenotypes for gene: FEZF1 were changed from to Hypogonadotropic hypogonadism 22, with or without anosmia 616030
Differences of Sex Development v0.103 FEZF1 Zornitza Stark Publications for gene: FEZF1 were set to
Differences of Sex Development v0.102 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3349 FEZF1 Zornitza Stark Marked gene: FEZF1 as ready
Mendeliome v0.3349 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3349 FEZF1 Zornitza Stark Phenotypes for gene: FEZF1 were changed from to Hypogonadotropic hypogonadism 22, with or without anosmia, MIM# 616030
Mendeliome v0.3348 FEZF1 Zornitza Stark Publications for gene: FEZF1 were set to
Mendeliome v0.3347 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3346 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Mendeliome v0.3346 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Marked gene: ESR2 as ready
Mendeliome v0.3345 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3345 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from to 46,XY disorder of sex development; Ovarian dysgenesis 8, MIM# 618187
Mendeliome v0.3344 ESR2 Zornitza Stark Publications for gene: ESR2 were set to
Mendeliome v0.3343 ESR2 Zornitza Stark Mode of inheritance for gene: ESR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29261182, 9861029, 30113650; Phenotypes: 46,XY disorder of sex development, Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.90 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from to Congenital disorder of glycosylation, type 1aa, MIM#610463
Differences of Sex Development v0.100 ESR2 Zornitza Stark Marked gene: ESR2 as ready
Differences of Sex Development v0.100 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.100 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from 46,XY Disorders of Sex Development to 46,XY Disorders of Sex Development; Ovarian dysgenesis 8, MIM# 618187
Differences of Sex Development v0.99 ESR2 Zornitza Stark Publications for gene: ESR2 were set to 29261182; 9861029
Differences of Sex Development v0.98 ESR2 Zornitza Stark Classified gene: ESR2 as Amber List (moderate evidence)
Differences of Sex Development v0.98 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.97 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30113650; Phenotypes: Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Marked gene: ERAL1 as ready
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Classified gene: ERAL1 as Red List (low evidence)
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 ERAL1 Zornitza Stark reviewed gene: ERAL1: Rating: RED; Mode of pathogenicity: None; Publications: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.96 MKKS Zornitza Stark reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: None
Differences of Sex Development v0.96 MKKS Zornitza Stark Marked gene: MKKS as ready
Differences of Sex Development v0.96 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome (MIM#236700)
Differences of Sex Development v0.95 MKKS Zornitza Stark Publications for gene: MKKS were set to
Differences of Sex Development v0.94 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.93 MKKS Zornitza Stark Classified gene: MKKS as Red List (low evidence)
Differences of Sex Development v0.93 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.89 ST3GAL3 Zornitza Stark Publications for gene: ST3GAL3 were set to
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Marked gene: CCDC115 as ready
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Classified gene: CCDC115 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.88 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.87 ST3GAL3 Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.86 B3GLCT Zornitza Stark Marked gene: B3GLCT as ready
Congenital Disorders of Glycosylation v0.86 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.86 ST3GAL3 Zornitza Stark Classified gene: ST3GAL3 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.86 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.85 B3GLCT Zornitza Stark Classified gene: B3GLCT as Green List (high evidence)
Congenital Disorders of Glycosylation v0.85 B3GLCT Zornitza Stark Gene: b3glct has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.84 PAPSS2 Zornitza Stark Marked gene: PAPSS2 as ready
Congenital Disorders of Glycosylation v0.84 PAPSS2 Zornitza Stark Gene: papss2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Marked gene: TMEM199 as ready
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Classified gene: TMEM199 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.84 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.83 PAPSS2 Zornitza Stark Phenotypes for gene: PAPSS2 were changed from to Brachyolmia 4 with mild epiphyseal and metaphyseal changes MIM#612847
Congenital Disorders of Glycosylation v0.82 TRIP11 Zornitza Stark Marked gene: TRIP11 as ready
Congenital Disorders of Glycosylation v0.82 TRIP11 Zornitza Stark Gene: trip11 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 KISS1R Crystle Lee reviewed gene: KISS1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164310, 31073722, 14573733; Phenotypes: Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.82 PAPSS2 Zornitza Stark Publications for gene: PAPSS2 were set to
Congenital Disorders of Glycosylation v0.81 PAPSS2 Zornitza Stark Mode of inheritance for gene: PAPSS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.80 CCDC115 Ain Roesley gene: CCDC115 was added
gene: CCDC115 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC115 were set to 26833332
Phenotypes for gene: CCDC115 were set to Congenital disorder of glycosylation, type IIo (MIM# 616828)
Penetrance for gene: CCDC115 were set to unknown
Review for gene: CCDC115 was set to GREEN
Added comment: PMID: 26833332
- 8 affecteds from 5 families. Abnormal N-and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts.
Sources: Literature
Congenital Disorders of Glycosylation v0.80 PAPSS2 Zornitza Stark Classified gene: PAPSS2 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.80 PAPSS2 Zornitza Stark Gene: papss2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.79 TRIP11 Zornitza Stark Mode of inheritance for gene: TRIP11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.78 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Congenital Disorders of Glycosylation v0.78 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.78 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.77 NUS1 Zornitza Stark Classified gene: NUS1 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.77 NUS1 Zornitza Stark Gene: nus1 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.76 TRIP11 Zornitza Stark Publications for gene: TRIP11 were set to
Congenital Disorders of Glycosylation v0.76 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from to Congenital disorder of glycosylation, type Ii (MIM# 607906)
Congenital Disorders of Glycosylation v0.75 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Congenital Disorders of Glycosylation v0.74 TRIP11 Zornitza Stark Classified gene: TRIP11 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.74 TRIP11 Zornitza Stark Gene: trip11 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.73 TRIP11 Zornitza Stark reviewed gene: TRIP11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Achondrogenesis, type IA MIM# 200600, Osteochondrodysplasia MIM# 184260; Mode of inheritance: None
Congenital Disorders of Glycosylation v0.73 ALG2 Zornitza Stark Mode of inheritance for gene: ALG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Marked gene: ATP6AP1 as ready
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Classified gene: ATP6AP1 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.72 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.71 ALG2 Zornitza Stark Classified gene: ALG2 as Red List (low evidence)
Congenital Disorders of Glycosylation v0.71 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.70 ST3GAL3 Paul De Fazio changed review comment from: 1 family described with West syndrome (PMID: 23252400). 2 unrelated consanguineous families described in PMID: 21907012. Functional testing supports abnormal enzyme function in all cases but no biochemical studies on patients.

ST3GAL3 located on chr1p34.1 encodes the β-galactoside-α2,3-sialyltransferase-III (ST3Gal-III), which in humans predominantly forms the sialyl Lewis a (sLe a) epitope on glycoproteins.

This gene is on the Invitae and EGL CDG panels.; to: 1 family described with West syndrome (PMID: 23252400). 2 unrelated consanguineous families described in PMID: 21907012 with ID. Functional testing supports abnormal enzyme function in all cases but no biochemical studies on patients.

ST3GAL3 located on chr1p34.1 encodes the β-galactoside-α2,3-sialyltransferase-III (ST3Gal-III), which in humans predominantly forms the sialyl Lewis a (sLe a) epitope on glycoproteins.

This gene is on the Invitae and EGL CDG panels.
Congenital Disorders of Glycosylation v0.70 ST3GAL3 Paul De Fazio reviewed gene: ST3GAL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 23252400, 21907012; Phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Classified gene: TRAPPC11 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.70 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.69 TRAPPC11 Zornitza Stark reviewed gene: TRAPPC11: Rating: AMBER; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108, 26912795, 27707803, 27862579, 28484880; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 MIM# 615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.69 XYLT2 Zornitza Stark Phenotypes for gene: XYLT2 were changed from to Spondyloocular syndrome MIM# 605822
Congenital Disorders of Glycosylation v0.68 XYLT2 Zornitza Stark Classified gene: XYLT2 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.68 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Gene: alg13 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.67 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Marked gene: PIGW as ready
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Gene: pigw has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.66 PIGW Zornitza Stark Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies
Congenital Disorders of Glycosylation v0.65 PIGW Zornitza Stark Publications for gene: PIGW were set to
Congenital Disorders of Glycosylation v0.64 PIGW Zornitza Stark Mode of inheritance for gene: PIGW was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.63 ALG13 Zornitza Stark Publications for gene: ALG13 were set to 22492991; 28887793; 26138355
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Marked gene: PIGM as ready
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Tag founder tag was added to gene: PIGM.
Mendeliome v0.3342 PIGM Paul De Fazio reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.62 PIGM Zornitza Stark Phenotypes for gene: PIGM were changed from to portal vein thrombosis; persistent absence seizures; macrocephaly; infantile-onset cerebrovascular thrombotic events
Congenital Disorders of Glycosylation v0.62 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Congenital Disorders of Glycosylation v0.61 PIGM Zornitza Stark Publications for gene: PIGM were set to
Congenital Disorders of Glycosylation v0.60 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital Disorders of Glycosylation v0.60 PIGM Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.59 PIGM Zornitza Stark Classified gene: PIGM as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.59 PIGM Zornitza Stark Gene: pigm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3342 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.58 ALG13 Zornitza Stark Classified gene: ALG13 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.58 ALG13 Zornitza Stark Gene: alg13 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.92 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097, 31483094; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3342 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Mendeliome v0.3342 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3342 DMRT1 Zornitza Stark Phenotypes for gene: DMRT1 were changed from to Azoospermia
Mendeliome v0.3341 DMRT1 Zornitza Stark Publications for gene: DMRT1 were set to
Mendeliome v0.3340 DMRT1 Zornitza Stark Mode of inheritance for gene: DMRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3339 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Mendeliome v0.3339 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Mendeliome v0.3338 DMRT1 Zornitza Stark reviewed gene: DMRT1: Rating: RED; Mode of pathogenicity: None; Publications: 31479588, 24934491, 29527098; Phenotypes: Azoospermia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Differences of Sex Development v0.90 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Differences of Sex Development v0.89 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Classified gene: DHCR24 as Red List (low evidence)
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Intellectual disability syndromic and non-syndromic v0.2769 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Intellectual disability syndromic and non-syndromic v0.2768 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Classified gene: LHX3 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Marked gene: CYB5A as ready
Differences of Sex Development v0.87 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Phenotypes for gene: CYB5A were changed from Methemoglobinemia and ambiguous genitalia 250790 to Methemoglobinemia and ambiguous genitalia, MIM# 250790
Differences of Sex Development v0.86 CYB5A Zornitza Stark Classified gene: CYB5A as Green List (high evidence)
Differences of Sex Development v0.86 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Differences of Sex Development v0.85 LHX3 Zornitza Stark Gene: lhx3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.84 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Differences of Sex Development v0.83 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Congenital Disorders of Glycosylation v0.57 B3GLCT Ain Roesley gene: B3GLCT was added
gene: B3GLCT was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: B3GLCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GLCT were set to 18199743; 16909395
Phenotypes for gene: B3GLCT were set to Peters-plus syndrome (MIM# 261540)
Penetrance for gene: B3GLCT were set to unknown
Review for gene: B3GLCT was set to GREEN
Added comment: PMID: 18199743
- 4 affecteds including 1 pair of siblings with mass spec analysis from patients' serum showing defective O-glycosylation

PMID: 16909395
- 20 affecteds from 15 families with no defective N-glycosylation however authors did not examine O-glycosylation and concluded that absence of defective glycosylation cannot be completely ruled out
Sources: Literature
Differences of Sex Development v0.82 CUL4B Zornitza Stark Marked gene: CUL4B as ready
Differences of Sex Development v0.82 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Differences of Sex Development v0.82 CUL4B Zornitza Stark Mode of inheritance for gene: CUL4B was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.81 CUL4B Zornitza Stark Classified gene: CUL4B as Green List (high evidence)
Differences of Sex Development v0.81 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Mendeliome v0.3338 CBX2 Zornitza Stark Marked gene: CBX2 as ready
Mendeliome v0.3338 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3338 CBX2 Zornitza Stark Phenotypes for gene: CBX2 were changed from to 46XY sex reversal 5, MIM# 613080
Mendeliome v0.3337 CBX2 Zornitza Stark Publications for gene: CBX2 were set to
Mendeliome v0.3336 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3335 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Mendeliome v0.3335 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: 19361780, 31719618, 23219007; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.80 CBX2 Zornitza Stark Marked gene: CBX2 as ready
Differences of Sex Development v0.80 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.80 CBX2 Zornitza Stark Phenotypes for gene: CBX2 were changed from to 46XY sex reversal 5, MIM# 613080
Differences of Sex Development v0.79 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.78 CBX2 Zornitza Stark Publications for gene: CBX2 were set to
Differences of Sex Development v0.77 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Differences of Sex Development v0.77 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Differences of Sex Development v0.76 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Mendeliome v0.3334 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Mendeliome v0.3334 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Mendeliome v0.3334 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Mendeliome v0.3333 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Mendeliome v0.3333 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8, MIM# 617564 to Meier-Gorlin syndrome 8, MIM# 617564
Skeletal dysplasia v0.35 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 617564 to Meier-Gorlin syndrome 8, MIM# 617564
Mendeliome v0.3332 ATF3 Zornitza Stark Marked gene: ATF3 as ready
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Mendeliome v0.3332 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Mendeliome v0.3332 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Marked gene: ATF3 as ready
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Marked gene: MKKS as ready
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Bardet Biedl syndrome v0.31 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231)
Bardet Biedl syndrome v0.30 MKKS Zornitza Stark Publications for gene: MKKS were set to
Bardet Biedl syndrome v0.29 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 LHB Crystle Lee reviewed gene: LHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 17761593, 28092701, 29476300, 22723313, 15602022; Phenotypes: Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 TMEM199 Paul De Fazio gene: TMEM199 was added
gene: TMEM199 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: TMEM199 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM199 were set to 26833330; 29321044
Phenotypes for gene: TMEM199 were set to Congenital disorder of glycosylation, type IIp MIM# 616829
Review for gene: TMEM199 was set to GREEN
gene: TMEM199 was marked as current diagnostic
Added comment: 4 patients from 3 unrelated families with a mild metabolic disorder primarily affecting the liver (PMID: 26833330). All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation.

A follow up publication described 3 more unrelated cases with protein glycosylation deficiency, supporting the original paper (PMID: 29321044).

Although this gene is red on PanelApp UK it has 2 green reviews (and no others).
Sources: Literature
Congenital Disorders of Glycosylation v0.57 PAPSS2 Naomi Baker reviewed gene: PAPSS2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22791835, 25594860, 31461705, 23633440, 9771708, 19474428.; Phenotypes: Brachyolmia 4 with mild epiphyseal and metaphyseal changes MIM#612847; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 NUS1 Belinda Chong reviewed gene: NUS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 610463, 25066056; Phenotypes: Congenital disorder of glycosylation, type 1aa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 TRIP11 Paul De Fazio reviewed gene: TRIP11: Rating: AMBER; Mode of pathogenicity: None; Publications: 29872333, 20089971, 30728324, 30518689; Phenotypes: Achondrogenesis, type IA MIM# 200600, Osteochondrodysplasia MIM# 184260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Differences of Sex Development v0.72 ERAL1 Elena Savva gene: ERAL1 was added
gene: ERAL1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERAL1 were set to PMID: 28449065
Phenotypes for gene: ERAL1 were set to Perrault syndrome 6 617565
Review for gene: ERAL1 was set to AMBER
Added comment: PMID: 28449065 - 3 unrelated patient with perrault syndrome with the same founder missense (p.Asn236Ile). Symptoms included hearing loss, premature ovarian failure, primary amenorrhea
Supported by functional analysis on patient cells, and transfected yeast reciprocating the phenotype.
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 ATP6AP1 Ain Roesley gene: ATP6AP1 was added
gene: ATP6AP1 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: ATP6AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6AP1 were set to PMID: 27231034
Phenotypes for gene: ATP6AP1 were set to immunodeficiency-47 (MIM# 300972)
Penetrance for gene: ATP6AP1 were set to unknown
Review for gene: ATP6AP1 was set to GREEN
Added comment: PMID: 27231034
- 11 males from 6 families with defective glycosylation
Sources: Literature
Differences of Sex Development v0.72 DMRT1 Elena Savva gene: DMRT1 was added
gene: DMRT1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DMRT1 were set to PMID: 31479588; 24934491; 29527098
Phenotypes for gene: DMRT1 were set to Azoospermia
Review for gene: DMRT1 was set to RED
Added comment: PMID: 31479588 - 1 patient with azoospermia and XY genotype. Also carries an additional variant in KLHL10

PMID: 24934491 - 6 patients with male infertility, however the 4 identified variants were also found in 2 controls and have a high frequency in the population (gnomAD). No functional studies.

PMID: 23555275 - Identifies CNVs in azoospermia patients, calls the gene a risk factor
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 ALG2 Ain Roesley reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: None; Publications: 12684507, 23404334, 24461433; Phenotypes: Congenital disorder of glycosylation, type Ii (MIM# 607906); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 DHCR24 Elena Savva reviewed gene: DHCR24: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9450875, 11519011; Phenotypes: Desmosterolosis 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson Marked gene: POLG2 as ready
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson Gene: polg2 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.28 POLG2 Bryony Thompson gene: POLG2 was added
gene: POLG2 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLG2 were set to 21555342; 27775730
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131
Review for gene: POLG2 was set to RED
Added comment: 3 unrelated cases have been reported with gastrointestinal symptoms and 3 different heterozygous missense (L153V, R369G, S423Y). All 3 missense are too common in gnomAD v2.1 for a dominant disease and biochemical assays demonstrated normal function for all expect R369G variants had reduced stimulation of processivity and decreased affinity for the catalytic subunit.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2766 LHX3 Crystle Lee reviewed gene: LHX3: Rating: RED; Mode of pathogenicity: None; Publications: 28302169; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CYB5A Elena Savva gene: CYB5A was added
gene: CYB5A was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CYB5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB5A were set to PMID: 22170710; 32051920
Phenotypes for gene: CYB5A were set to Methemoglobinemia and ambiguous genitalia 250790
Review for gene: CYB5A was set to GREEN
Added comment: PMID: 22170710 - 3 siblings with 46,XY DSD, sex steroid deficiency, female genitalia and a homozygous missense variant. Supported by LOF functional studies. Mineralocorticoids and glucocorticoids were normal.

PMID: 32051920 - 1 female with a homozygous missense, no DSD but methemoglobinemia. All female genitalia are normal and she has had a normal female child.
Paper reviews prior reports and notes an additional 2 unrelated homozygous reports of 46 XY DSD patients with normal Methemoglobin. All variants were rare/absent (gnomAD) and PTCs.
Sources: Expert list
Differences of Sex Development v0.72 LHX3 Crystle Lee reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302169, 17327381, 30262920; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CUL4B Elena Savva gene: CUL4B was added
gene: CUL4B was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CUL4B was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CUL4B were set to PMID: 25385192
Phenotypes for gene: CUL4B were set to Mental retardation, X-linked, syndromic 15 (Cabezas type) 300354
Review for gene: CUL4B was set to GREEN
Added comment: PMID: 25385192 - 25 patients (11 families) with syndromic features including hypogonadism (85%) and gynecomastia (33%)
Sources: Expert list
Congenital Disorders of Glycosylation v0.57 TRAPPC11 Paul De Fazio changed review comment from: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking
" (PMID: 28484880)
Sources: Literature; to: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking" (PMID: 28484880)
Sources: Literature
Congenital Disorders of Glycosylation v0.57 TRAPPC11 Paul De Fazio gene: TRAPPC11 was added
gene: TRAPPC11 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC11 were set to 23830518; 26322222; 29855340; 30105108; 26912795; 27707803; 27862579; 28484880
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, autosomal recessive 18 MIM# 615356
Review for gene: TRAPPC11 was set to GREEN
gene: TRAPPC11 was marked as current diagnostic
Added comment: Association with a multisystem disorder including muscular dystrophy is established (green in our Muscular dystrophy gene list).

Biochemical studies in zebrafish show that TRAPPC11 is involved in protein glycosylation (PMID: 26912795). The authors proposed that TRAPPC11 may function as a scaffold for enzymes of protein N-glycosylation or as a cofactor for an enzyme in lipid-linked oligosaccharide synthesis.

Patients with homozygous or compound heterozygous TRAPPC11 variants have been found to have abnormal glycosylation of the LAMP1/LAMP2 proteins (PMID: 23830518, 27707803). TRAPPC11 has been implicated in α-dystroglycan hypoglycosylation (PMID: 29855340).

A patient with biallelic TRAPPC11 variants was found to have abnormal transferrin and Apo CIII glycosylation patterns, consistent with a CDG (PMID: 27862579).

TRAPPC11-CDG has been suggested to be a "Novel CDG in ER to Golgi trafficking
" (PMID: 28484880)
Sources: Literature
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Marked gene: NR3C1 as ready
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Gene: nr3c1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Phenotypes for gene: NR3C1 were changed from to Glucocorticoid resistance (MIM#615962)
Differences of Sex Development v0.71 NR3C1 Zornitza Stark Publications for gene: NR3C1 were set to
Differences of Sex Development v0.70 NR3C1 Zornitza Stark Mode of inheritance for gene: NR3C1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.69 CBX2 Elena Savva reviewed gene: CBX2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 19361780, 31719618, 23219007; Phenotypes: ?46XY sex reversal 5 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Only single patient reported in 2017. Patient presented with microstomia, thick lips, micrognathia, bilateral microtia, low set ears and bilateral cryptorchidism.
Sources: Expert Review
Mendeliome v0.3331 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Compound heterozgyous variants reported in one patient. Insufficient evidence supporting gene disease association
Sources: Expert Review
Congenital Disorders of Glycosylation v0.57 XYLT2 Paul De Fazio edited their review of gene: XYLT2: Changed phenotypes: Spondyloocular syndrome MIM# 605822
Skeletal dysplasia v0.34 MCM5 Crystle Lee reviewed gene: MCM5: Rating: RED; Mode of pathogenicity: None; Publications: 28198391; Phenotypes: ?Meier-Gorlin syndrome 8 (MIM#617564); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 XYLT2 Paul De Fazio gene: XYLT2 was added
gene: XYLT2 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT2 were set to 26027496; 26987875; 30891060; 28484880
Review for gene: XYLT2 was set to GREEN
gene: XYLT2 was marked as current diagnostic
Added comment: 5 unrelated individuals/families in total described with Spondylo-Ocular Syndrome (PMID: 26027496, 26987875, 30891060).

XYLT2-CDG has been referred to as a "proteoglycan ‘linker’ glycan disorder" (PMID: 28484880)
Sources: Literature
Differences of Sex Development v0.69 MKKS Crystle Lee reviewed gene: MKKS: Rating: AMBER; Mode of pathogenicity: None; Publications: 10973251, 26900326, 10973238; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 PIGW Dean Phelan changed review comment from: OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.; to: OMIM - Glycosylphosphatidylinositol biosynthesis defect 11, AR

Function - Glycosylphosphatidylinositol (GPI) is a complex glycolipid that anchors many proteins to the cell surface. PIGW acts in the third step of GPI biosynthesis and acylates the inositol ring of phosphatidylinositol

Clingen - no association with CGD

PMID: 24367057 - (2013) - A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW.

PMID: 27626616 - (2016) Two second-degree cousins with unexplained patterns of seizures. Next-generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw-defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. The patients' phenotype is remarkably different from the phenotype of the only other described individual with PIGW mutations.

PMID: 30813920 - (2019) A Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy. A 70-day-old boy presented with fever and cough over 20 days in duration at the time of admission. At the age of 6 months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G > A and c.462A > T mutations

PMID: 32198969 - (2020) A new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections.

Summary - Multiple unrelated families reported with different recessive variants either homozygous or compound heterozygous. Functional studies showed impaired enzymatic activity
Congenital Disorders of Glycosylation v0.57 PIGW Dean Phelan reviewed gene: PIGW: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24367057, 27626616, 30813920, 32198969; Phenotypes: intractable seizures, West syndrome, severe developmental delay, dysmorphic facial features, hyperphosphatasia, epilepsy, recurrent respiratory infections, hypotonia, stereotypies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 ATF3 Elena Savva reviewed gene: ATF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.69 ATF3 Elena Savva reviewed gene: ATF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Bardet Biedl syndrome v0.28 MKKS Crystle Lee reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973251; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 PIGM Dean Phelan reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 NR3C1 Crystle Lee reviewed gene: NR3C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30158362; Phenotypes: Glucocorticoid resistance (MIM#615962); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Disorders of Glycosylation v0.57 ALG13 Ain Roesley reviewed gene: ALG13: Rating: AMBER; Mode of pathogenicity: None; Publications: 22492991, 28887793, 26138355; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); 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 v0.2766 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from to Neuropathy, hereditary sensory, type ID, MIM# 613708; Spastic paraplegia 3A, autosomal dominant, MIM# 182600
Intellectual disability syndromic and non-syndromic v0.2765 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Intellectual disability syndromic and non-syndromic v0.2764 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Classified gene: ATL1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: RED; Mode of pathogenicity: None; Publications: 21336785, 28736820, 29180453, 29691679, 31236401; Phenotypes: Neuropathy, hereditary sensory, type ID, MIM# 613708, Spastic paraplegia 3A, autosomal dominant, MIM# 182600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3331 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Mendeliome v0.3331 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Mendeliome v0.3331 CNPY3 Zornitza Stark Phenotypes for gene: CNPY3 were changed from to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Mendeliome v0.3330 CNPY3 Zornitza Stark Publications for gene: CNPY3 were set to
Mendeliome v0.3329 CNPY3 Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3328 CNPY3 Zornitza Stark reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Classified gene: CNPY3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.752 CNPY3 Zornitza Stark Phenotypes for gene: CNPY3 were changed from to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Genetic Epilepsy v0.751 CNPY3 Zornitza Stark Publications for gene: CNPY3 were set to
Genetic Epilepsy v0.750 CNPY3 Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3328 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3328 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Mendeliome v0.3328 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Mendeliome v0.3327 KIF21B Zornitza Stark gene: KIF21B was added
gene: KIF21B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Mode of pathogenicity for gene: KIF21B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Marked gene: PAX1 as ready
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Classified gene: TMEM106B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Classified gene: TMEM106B as Amber List (moderate evidence)
Genetic Epilepsy v0.749 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3326 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3326 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Green List (high evidence)
Mendeliome v0.3326 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Mendeliome v0.3325 TBC1D2B Zornitza Stark gene: TBC1D2B was added
gene: TBC1D2B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.
Sources: Expert Review
Genetic Epilepsy v0.748 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Green List (high evidence)
Genetic Epilepsy v0.748 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Classified gene: CEP120 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3322 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Mendeliome v0.3322 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3321 CCDC174 Zornitza Stark gene: CCDC174 was added
gene: CCDC174 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3320 ACOX2 Zornitza Stark Classified gene: ACOX2 as Green List (high evidence)
Mendeliome v0.3320 ACOX2 Zornitza Stark Gene: acox2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ACOX2 Zornitza Stark edited their review of gene: ACOX2: Added comment: Third family reported.; Changed rating: GREEN; Changed publications: 27647924, 27884763, 29287774
Peroxisomal Disorders v0.4 ACOX2 Zornitza Stark Publications for gene: ACOX2 were set to 27647924; 27884763
Peroxisomal Disorders v0.3 ACOX2 Zornitza Stark Classified gene: ACOX2 as Green List (high evidence)
Peroxisomal Disorders v0.3 ACOX2 Zornitza Stark Gene: acox2 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.2 ACOX2 Zornitza Stark edited their review of gene: ACOX2: Added comment: Third family reported.; Changed rating: GREEN; Changed publications: 29287774; Changed phenotypes: Bile acid synthesis defect, congenital, 6, 617308; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Marked gene: ACOX2 as ready
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Classified gene: ACOX2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3319 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Mendeliome v0.3319 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Mendeliome v0.3318 ABCA2 Zornitza Stark gene: ABCA2 was added
gene: ABCA2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Expert Review
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Genetic Epilepsy v0.747 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Autism v0.103 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Autism v0.103 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Autism v0.103 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Autism v0.102 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Autism v0.101 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Autism v0.100 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.11 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Angelman Rett like syndromes v0.10 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Angelman Rett like syndromes v0.9 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.8 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3317 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Mendeliome v0.3317 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3317 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Mendeliome v0.3316 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Mendeliome v0.3315 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3314 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Classified gene: HERC2 as Green List (high evidence)
Genetic Epilepsy v0.746 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2752 HERC2 Zornitza Stark Publications for gene: HERC2 were set to 23243086; 23065719
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Classified gene: HERC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3314 ALOX12 Zornitza Stark Marked gene: ALOX12 as ready
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3314 ALOX12 Zornitza Stark Classified gene: ALOX12 as Red List (low evidence)
Mendeliome v0.3314 ALOX12 Zornitza Stark Gene: alox12 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ALOX12 Zornitza Stark reviewed gene: ALOX12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3313 ETF1 Zornitza Stark Marked gene: ETF1 as ready
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3313 ETF1 Zornitza Stark Classified gene: ETF1 as Red List (low evidence)
Mendeliome v0.3313 ETF1 Zornitza Stark Gene: etf1 has been classified as Red List (Low Evidence).
Mendeliome v0.3312 ETF1 Zornitza Stark reviewed gene: ETF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2750 TTI1 Zornitza Stark commented on gene: TTI1: Two unrelated consanguineous families previously described with homozygous missense variants, both in large cohort papers with multiple candidate genes in inbred population. No functional evidence provided, segregation uninformative.
Mendeliome v0.3312 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from to Intellectual disability
Mendeliome v0.3311 TTI1 Zornitza Stark Publications for gene: TTI1 were set to
Mendeliome v0.3310 TTI1 Zornitza Stark Mode of inheritance for gene: TTI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 CNPY3 Konstantinos Varvagiannis gene: CNPY3 was added
gene: CNPY3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CNPY3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNPY3 were set to 29394991; 30237576
Phenotypes for gene: CNPY3 were set to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Penetrance for gene: CNPY3 were set to Complete
Review for gene: CNPY3 was set to GREEN
Added comment: Biallelic CNPY3 mutations cause Epileptic encephalopathy, early infantile, 60 (MIM 617929).

The phenotype including among others hypotonia, intractable seizures, DD and ID has been first reported by Mutoh et al (2018 - PMID: 29394991) in 3 subjects from 2 families. Evidence was provided for the role of the gene (incl. mouse model) and pathogenicity of the identified variants (resulting in LoF).

Another subject with similar features of hypotonia, DD, intractable epilepsy, feeding problems has been described briefly by Maddirevula et al (2019 - PMID: 30237576).
Sources: Literature
Genetic Epilepsy v0.745 CNPY3 Konstantinos Varvagiannis reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 KIF21B Konstantinos Varvagiannis gene: KIF21B was added
gene: KIF21B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Penetrance for gene: KIF21B were set to unknown
Mode of pathogenicity for gene: KIF21B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 PAX1 Konstantinos Varvagiannis gene: PAX1 was added
gene: PAX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAX1 were set to 29681087; 23851939; 28657137
Phenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560
Penetrance for gene: PAX1 were set to Complete
Review for gene: PAX1 was set to AMBER
Added comment: Biallelic PAX1 pathogenic variants cause Otofaciocervical syndrome 2 (OMIM 615560).

Brief review of the literature suggests 3 relevant publications to date (04-07-2020).

2 individuals with DD and ID have been reported (Patil et al, 2018 - PMID: 29681087 and Pohl et al, 2013 - PMID: 23851939). Other subjects reported were only evaluated as newborns(mostly)/infants [Paganini et al, 2017 - PMID: 28657137, Patil et al, 2018 - PMID: 29681087].

While the first report by Pohl et al identified a homozygous missense variant supported by functional studies [NM_006192.5:c.497G>T - p.(Gly166Val)] subsequent ones identified homozygosity for pLoF mutations [Patil et al: NM_006192.4:c.1173_1174insGCCCG / Paganini et al: NM_006192:c.1104C>A - p.(Cys368*)].

As discussed by Pohl et al:

PAX1 encodes a transcription factor with critical role in pattern formation during embryogenesis. Study of the mouse Gly157Val (equivalent to human Gly166Val) Pax1 variant suggested reduced binding affinity (reduced transactivation of a regulatory sequence of the Nkx3-2 promoter) and hypofunctional nature of this variant.

Mouse models seem to recapitulate features of the disorder (skeletal, immunodeficiency) while the role of Pax1 in hearing process was thought to be supported by early expression (P6) in mouse cochlea.

Overall this gene can be considered for inclusion in the ID panel with amber/green rating.
Sources: Literature, Radboud University Medical Center, Nijmegen
Intellectual disability syndromic and non-syndromic v0.2750 TMEM106B Konstantinos Varvagiannis gene: TMEM106B was added
gene: TMEM106B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)
Penetrance for gene: TMEM106B were set to Complete
Mode of pathogenicity for gene: TMEM106B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TMEM106B was set to GREEN
Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021).

While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].

All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).

As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.

Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.

Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.

Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating.
Sources: Literature
Genetic Epilepsy v0.745 TMEM106B Konstantinos Varvagiannis gene: TMEM106B was added
gene: TMEM106B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)
Penetrance for gene: TMEM106B were set to Complete
Mode of pathogenicity for gene: TMEM106B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TMEM106B was set to AMBER
Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021).

While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].

All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).

As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.

Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.

Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.

Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating.
Sources: Literature
Genetic Epilepsy v0.745 TBC1D2B Konstantinos Varvagiannis gene: TBC1D2B was added
gene: TBC1D2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Penetrance for gene: TBC1D2B were set to Complete
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants.

Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations.

All were born to non-consanguineous couples and additional investigations were performed in some.

Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses.

In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts.

TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation.

Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.

Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 TBC1D2B Konstantinos Varvagiannis gene: TBC1D2B was added
gene: TBC1D2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Penetrance for gene: TBC1D2B were set to Complete
Review for gene: TBC1D2B was set to AMBER
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants.

Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations.

All were born to non-consanguineous couples and additional investigations were performed in some.

Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses.

In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts.

TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation.

Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.

Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 EXOC2 Konstantinos Varvagiannis gene: EXOC2 was added
gene: EXOC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Penetrance for gene: EXOC2 were set to Complete
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations.

Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3).

Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals.

EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis.

Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration.

An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2.

Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome).

The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CEP120 Konstantinos Varvagiannis gene: CEP120 was added
gene: CEP120 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP120 were set to 27208211
Phenotypes for gene: CEP120 were set to Joubert syndrome 31 (MIM 617761); Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300)
Penetrance for gene: CEP120 were set to Complete
Review for gene: CEP120 was set to GREEN
Added comment: Pathogenic CEP120 variants have been reported in recessive ciliopathies, namely Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) and Joubert syndrome 31 (MIM 617761).

The former is associated with a severe/lethal outcome (4 unrelated infants described by Shaheen et al 2015 - PMID: 25361962, 2 fetuses reported by Roosing et al 2016 - PMID: 27208211).

Roosing et al however, also provided details on 4 unrelated subjects with Joubert syndrome diagnosis. All presented with a neurologic phenotype of hypotonia, DD, cognitive impairment and exhibited a molar tooth sign.

As a result, this gene can be considered for inclusion in the ID panel with green rating (>3 individuals/variants, consistent ciliopathy phenotype).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CCDC174 Konstantinos Varvagiannis gene: CCDC174 was added
gene: CCDC174 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Penetrance for gene: CCDC174 were set to Complete
Mode of pathogenicity for gene: CCDC174 was set to Other
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816).

Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype.

Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ACOX2 Konstantinos Varvagiannis gene: ACOX2 was added
gene: ACOX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763; 29287774
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6 - 617308
Penetrance for gene: ACOX2 were set to unknown
Review for gene: ACOX2 was set to RED
Added comment: Biallelic pathogenic ACOX2 variants cause Bile acid synthesis defect, congenital, 6 (MIM 617308). Overall the phenotype corresponds to an IEM/peroxisomal disorder.

As per 01-07-2020 there are 3 reports, briefly reviewed :

- Vilarinho et al [2016 - PMID: 27647924] provided details on an 8-year-old boy with ID.
- Monte et al [2017 - PMID: 27884763] described a 16 year old male with sustained elevation of transaminases *without* accompanying neurologic symptomatology (as they comment).
- Ferdinandusse et al [2018 - PMID: 29287774] reported on a girl deceased at the age of few months.

Please consider inclusion in the ID panel with amber/red rating pending further reports.
Sources: Literature
Genetic Epilepsy v0.745 ABCA2 Konstantinos Varvagiannis gene: ABCA2 was added
gene: ABCA2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Penetrance for gene: ABCA2 were set to Complete
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ABCA2 Konstantinos Varvagiannis gene: ABCA2 was added
gene: ABCA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Penetrance for gene: ABCA2 were set to Complete
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Genetic Epilepsy v0.745 HERC2 Konstantinos Varvagiannis gene: HERC2 was added
gene: HERC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HERC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HERC2 were set to 23065719; 23243086; 30902390; 32571899; 27848944; 26077850; 27759030
Phenotypes for gene: HERC2 were set to Mental retardation, autosomal recessive 38 (MIM 615516)
Penetrance for gene: HERC2 were set to Complete
Review for gene: HERC2 was set to GREEN
Added comment: Biallelic pathogenic HERC2 variants cause Mental retardation, autosomal recessive 38 (MIM 615516).

The current review is based mostly on the information provided by Elpidorou et al (2020 - PMID: 32571899) summarizing the findings in several affected individuals as published in the literature. ID was a universal feature among them (27/27) and seizures were reported in some (9/27):
- 22 subjects from Amish/Mennonite families were homozygous for p.Pro594Leu [NM_004667.5(HERC2):c.1781C>T] (Puffenberger et al 2012 - PMID: 23065719, Harlalka et al 2013 - PMID: 23243086, Abraham et al - PMID: 30902390)
- 2 additional patients were homozygous for another missense SNV [NM_004667.5(HERC2):c.4625G>A - p.Arg1542His] (Abraham et al 2019 - PMID: 30902390)
- 3 sibs born to consanguineous parents, homozygous for NM_004667.5:c.13767_13770delTGAA - p.(Asn4589LysTer4598)] as described by Elpidorou et al.
- 1 male homozygous 286 kb deletion spanning several 5' exons of HERC2 as well as the first exons of OCA2 was described by Morice-Picard et al (2016 - PMID: 27759030). Despite a neurological presentation (axial hypotonia, peripheral hypertonia, extrapyramidal symptoms and uncoordinated movements) further information was not available.

Apart from the cases summarized by Elpidorou et al, there have been few additional ones e.g. :
- Trujillano et al (2017 - PMID: 27848944) reported briefly on a patient, homozygous for NM_004667.5:c.4676-1G>A displaying seizures, hypotonia, global DD, "Encephalopathy" and abnormality of the liver.
- Yavarna et al (2015 - PMID: 26077850) provided few details with on an individual with primarily 'neurocognitive' phenotype but rather atypical presentation (MRI abnormalities, TGA, VSD, renal anomaly, growth retardation, hearing loss) due to p.Q3164X variant (recessive inheritance was specified).

Several lines of evidence support an important role for the protein encoded (an E3 ubiquitin protein ligase, interacting also with UBE3A, involved in several cellular processes incl. cell cycle regulation, spindle formation during mitosis, mitochondrial functions, DNA damage responses by targeting proteins such as XPA) as well as the effect of the reported variants (mRNA studies, Western blot, detection of a fusion transcript in the case of the deletion, etc).

Individuals from the Amish families displayed Angelman-like features (in line with HERC2-UBE3A interaction) with - among others - gait instability. Mouse models recapitulate some of these features (e.g. the movement disorder) as extensively discussed by Abraham et al.

Overall this gene can be included in the ID and epilepsy panels with green rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 HERC2 Konstantinos Varvagiannis reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.69 PCSK1 Zornitza Stark reviewed gene: PCSK1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Marked gene: PCSK1 as ready
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Phenotypes for gene: PCSK1 were changed from to Obesity with impaired prohormone processing (MIM#600955)
Differences of Sex Development v0.68 PCSK1 Zornitza Stark Publications for gene: PCSK1 were set to
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Classified gene: PCSK1 as Amber List (moderate evidence)
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Marked gene: PROK2 as ready
Differences of Sex Development v0.66 PROK2 Zornitza Stark Added comment: Comment when marking as ready: Evidence supporting association between bi-allelic variants causing IHH is stronger than for mono-allelic disease.
Differences of Sex Development v0.66 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Phenotypes for gene: PROK2 were changed from to Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628)
Differences of Sex Development v0.65 PROK2 Zornitza Stark Publications for gene: PROK2 were set to
Differences of Sex Development v0.64 PROK2 Zornitza Stark Mode of inheritance for gene: PROK2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.63 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Differences of Sex Development v0.63 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.63 PROP1 Zornitza Stark Phenotypes for gene: PROP1 were changed from to Pituitary hormone deficiency, combined, 2 (MIM#262600)
Differences of Sex Development v0.62 PROP1 Zornitza Stark Publications for gene: PROP1 were set to
Differences of Sex Development v0.61 PROP1 Zornitza Stark Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Phenotypes for gene: RPL10 were changed from to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Intellectual disability syndromic and non-syndromic v0.2749 RPL10 Zornitza Stark Publications for gene: RPL10 were set to
Intellectual disability syndromic and non-syndromic v0.2748 RPL10 Zornitza Stark Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.60 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.60 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Marked gene: SEMA3E as ready
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Classified gene: SEMA3E as Red List (low evidence)
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.365 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Deafness_IsolatedAndComplex v0.364 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Deafness_IsolatedAndComplex v0.363 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.56 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Differences of Sex Development v0.56 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.56 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266) to Kallman syndrome; PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Classified gene: SOX10 as Green List (high evidence)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Marked gene: TAC3 as ready
Differences of Sex Development v0.54 TAC3 Zornitza Stark Gene: tac3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Phenotypes for gene: TAC3 were changed from to Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839)
Differences of Sex Development v0.53 TAC3 Zornitza Stark Publications for gene: TAC3 were set to
Differences of Sex Development v0.52 TAC3 Zornitza Stark Mode of inheritance for gene: TAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.51 TOE1 Zornitza Stark Marked gene: TOE1 as ready
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.51 TOE1 Zornitza Stark Classified gene: TOE1 as Green List (high evidence)
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3309 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Mendeliome v0.3309 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Mendeliome v0.3308 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Osteopetrosis v0.3 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Osteopetrosis v0.3 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteopetrosis v0.3 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Osteopetrosis v0.3 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteopetrosis v0.2 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Osteopetrosis. Sources: Literature
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Marked gene: SGMS2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Classified gene: SGMS2 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.26 SGMS2 Bryony Thompson Gene: sgms2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.25 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Osteogenesis Imperfecta. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments.
2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Marked gene: UNC45A as ready
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Gene: unc45a has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.24 UNC45A Bryony Thompson Phenotypes for gene: UNC45A were changed from to cholestasis; congenital diarrhea; impaired hearing; bone fragility
Osteogenesis Imperfecta and Osteoporosis v0.23 UNC45A Bryony Thompson Publications for gene: UNC45A were set to
Osteogenesis Imperfecta and Osteoporosis v0.22 UNC45A Bryony Thompson Mode of inheritance for gene: UNC45A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.1 Seb Lunke Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Pituitary hormone deficiency v0.0 ZSWIM6 Seb Lunke gene: ZSWIM6 was added
gene: ZSWIM6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZSWIM6 were set to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (617865); Acromelic frontonasal dysostosis (603671)
Pituitary hormone deficiency v0.0 ZIC2 Seb Lunke gene: ZIC2 was added
gene: ZIC2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZIC2 were set to 24706429
Phenotypes for gene: ZIC2 were set to Holoprosencephaly 5 (609637)
Pituitary hormone deficiency v0.0 WDR11 Seb Lunke gene: WDR11 was added
gene: WDR11 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: WDR11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: WDR11 were set to Hypogonadotropic hypogonadism 14 with or without anosmia (614858)
Pituitary hormone deficiency v0.0 TGIF1 Seb Lunke gene: TGIF1 was added
gene: TGIF1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: TGIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TGIF1 were set to 23476075
Phenotypes for gene: TGIF1 were set to Holoprosencephaly 4 (142946)
Pituitary hormone deficiency v0.0 SLC20A1 Seb Lunke gene: SLC20A1 was added
gene: SLC20A1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SLC20A1 was set to Unknown
Phenotypes for gene: SLC20A1 were set to No OMIM number
Pituitary hormone deficiency v0.0 SLC15A4 Seb Lunke gene: SLC15A4 was added
gene: SLC15A4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SLC15A4 was set to Unknown
Publications for gene: SLC15A4 were set to 29261175
Phenotypes for gene: SLC15A4 were set to No OMIM number
Pituitary hormone deficiency v0.0 SIX3 Seb Lunke gene: SIX3 was added
gene: SIX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SIX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SIX3 were set to Holoprosencephaly 2 (157170)
Pituitary hormone deficiency v0.0 RBM28 Seb Lunke gene: RBM28 was added
gene: RBM28 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RBM28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM28 were set to 20231366
Phenotypes for gene: RBM28 were set to ANE syndrome; ?Alopecia, neurologic defects, and endocrinopathy syndrome (612079)
Pituitary hormone deficiency v0.0 PTCH1 Seb Lunke gene: PTCH1 was added
gene: PTCH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PTCH1 were set to 11941477
Phenotypes for gene: PTCH1 were set to Holoprosencephaly 7 (610828)
Pituitary hormone deficiency v0.0 PSTPIP1 Seb Lunke gene: PSTPIP1 was added
gene: PSTPIP1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PSTPIP1 were set to Holoprosencephaly; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (604416)
Pituitary hormone deficiency v0.0 POLR3A Seb Lunke gene: POLR3A was added
gene: POLR3A was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (607694)
Pituitary hormone deficiency v0.0 PAX6 Seb Lunke gene: PAX6 was added
gene: PAX6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAX6 were set to 25342853
Phenotypes for gene: PAX6 were set to Aniridia (106210)
Pituitary hormone deficiency v0.0 NODAL Seb Lunke gene: NODAL was added
gene: NODAL was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: NODAL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: NODAL were set to Holoprosencephaly; Heterotaxy, visceral, 5 (270100)
Pituitary hormone deficiency v0.0 HNRNPU Seb Lunke gene: HNRNPU was added
gene: HNRNPU was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: HNRNPU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HNRNPU were set to Epileptic encephalopathy, early infantile, 54 (617391)
Pituitary hormone deficiency v0.0 HHIP Seb Lunke gene: HHIP was added
gene: HHIP was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: HHIP was set to Unknown
Phenotypes for gene: HHIP were set to No OMIM number
Pituitary hormone deficiency v0.0 GPR161 Seb Lunke gene: GPR161 was added
gene: GPR161 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GPR161 was set to Unknown
Publications for gene: GPR161 were set to 25322266
Phenotypes for gene: GPR161 were set to No OMIM number; pituitary stalk interruption syndrome
Pituitary hormone deficiency v0.0 GHRH Seb Lunke gene: GHRH was added
gene: GHRH was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GHRH was set to Unknown
Publications for gene: GHRH were set to 15155578
Phenotypes for gene: GHRH were set to No OMIM number; ?Isolated growth hormone deficiency due to defect in GHRF
Pituitary hormone deficiency v0.0 FOXH1 Seb Lunke gene: FOXH1 was added
gene: FOXH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FOXH1 was set to Unknown
Phenotypes for gene: FOXH1 were set to Holoprosencephaly; No OMIM number
Pituitary hormone deficiency v0.0 BMP4 Seb Lunke gene: BMP4 was added
gene: BMP4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: BMP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BMP4 were set to 24289245
Phenotypes for gene: BMP4 were set to Microphthalmia, syndromic 6 (607932)
Pituitary hormone deficiency v0.0 BMP2 Seb Lunke gene: BMP2 was added
gene: BMP2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: BMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BMP2 were set to 24289245
Phenotypes for gene: BMP2 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (617877)
Pituitary hormone deficiency v0.0 ARNT2 Seb Lunke gene: ARNT2 was added
gene: ARNT2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ARNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARNT2 were set to 24022475
Phenotypes for gene: ARNT2 were set to ?Webb-Dattani syndrome (615926)
Pituitary hormone deficiency v0.0 TCF7L1 Seb Lunke gene: TCF7L1 was added
gene: TCF7L1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: TCF7L1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TCF7L1 were set to 26764381
Phenotypes for gene: TCF7L1 were set to No OMIM number; pituitary hormone deficiency
Pituitary hormone deficiency v0.0 SHH Seb Lunke gene: SHH was added
gene: SHH was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SHH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SHH were set to 22897141
Phenotypes for gene: SHH were set to Microphthalmia with coloboma 5 (611638); Holoprosencephaly 3 (142945)
Pituitary hormone deficiency v0.0 KCNQ1 Seb Lunke gene: KCNQ1 was added
gene: KCNQ1 was added to Pituitary hormone deficiency. Sources: Expert Review Amber,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 Pituitary hormone deficiency; Long QT syndrome 1 (192500)
Pituitary hormone deficiency v0.0 CDON Seb Lunke gene: CDON was added
gene: CDON was added to Pituitary hormone deficiency. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CDON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDON were set to 21802063; 26529631
Phenotypes for gene: CDON were set to Holoprosencephaly 11 (614226)
Pituitary hormone deficiency v0.0 TBX19 Seb Lunke gene: TBX19 was added
gene: TBX19 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TBX19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBX19 were set to 22170728; 11290323; 15476446
Phenotypes for gene: TBX19 were set to Adrenocorticotropic hormone deficiency (201400)
Pituitary hormone deficiency v0.0 SOX3 Seb Lunke gene: SOX3 was added
gene: SOX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SOX3 were set to 24346842; 15800844; 21289259; 24737742
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked (312000); Mental retardation, X-linked, with isolated growth hormone deficiency (300123)
Pituitary hormone deficiency v0.0 SOX2 Seb Lunke gene: SOX2 was added
gene: SOX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX2 were set to 29371155; 16932809; 30450772
Phenotypes for gene: SOX2 were set to Microphthalmia, syndromic 3 (206900)
Pituitary hormone deficiency v0.0 PROP1 Seb Lunke gene: PROP1 was added
gene: PROP1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2 (262600)
Pituitary hormone deficiency v0.0 PROKR2 Seb Lunke gene: PROKR2 was added
gene: PROKR2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PROKR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PROKR2 were set to 22319038; 25678757; 25759380
Phenotypes for gene: PROKR2 were set to Hypogonadotropic hypogonadism 3 with or without anosmia (244200)
Pituitary hormone deficiency v0.0 POU1F1 Seb Lunke gene: POU1F1 was added
gene: POU1F1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: POU1F1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POU1F1 were set to Pituitary hormone deficiency, combined, 1 (613038)
Pituitary hormone deficiency v0.0 PNPLA6 Seb Lunke gene: PNPLA6 was added
gene: PNPLA6 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 25033069
Phenotypes for gene: PNPLA6 were set to Oliver-McFarlane syndrome (275400); Spastic paraplegia 39, autosomal recessive (612020); Boucher-Neuhauser syndrome (215470)
Pituitary hormone deficiency v0.0 PITX2 Seb Lunke gene: PITX2 was added
gene: PITX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PITX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PITX2 were set to Anterior segment dysgenesis 4 (137600); Axenfeld-Rieger syndrome, type 1 (180500)
Pituitary hormone deficiency v0.0 OTX2 Seb Lunke gene: OTX2 was added
gene: OTX2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OTX2 were set to 19965921; 22715480; 18628516; 18728160
Phenotypes for gene: OTX2 were set to Pituitary hormone deficiency, combined, 6 (613986); Microphthalmia, syndromic 5 (610125)
Pituitary hormone deficiency v0.0 LHX4 Seb Lunke gene: LHX4 was added
gene: LHX4 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: LHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX4 were set to 18073311; 18445675; 11567216
Phenotypes for gene: LHX4 were set to Pituitary hormone deficiency, combined, 4 (262700)
Pituitary hormone deficiency v0.0 LHX3 Seb Lunke gene: LHX3 was added
gene: LHX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: LHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LHX3 were set to Pituitary hormone deficiency, combined, 3 (221750)
Pituitary hormone deficiency v0.0 IGSF1 Seb Lunke gene: IGSF1 was added
gene: IGSF1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: IGSF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IGSF1 were set to 23143598; 23966245; 26302767
Phenotypes for gene: IGSF1 were set to Hypothyroidism, central, and testicular enlargement (300888)
Pituitary hormone deficiency v0.0 HESX1 Seb Lunke gene: HESX1 was added
gene: HESX1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: HESX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HESX1 were set to 14561704; 26781211; 11136712; 16940453
Phenotypes for gene: HESX1 were set to Growth hormone deficiency with pituitary anomalies (182230); Pituitary hormone deficiency, combined, 5 (182230)
Pituitary hormone deficiency v0.0 GNRHR Seb Lunke gene: GNRHR was added
gene: GNRHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GNRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRHR were set to Hypogonadotropic hypogonadism 7 without anosmia (146110)
Pituitary hormone deficiency v0.0 GLI3 Seb Lunke gene: GLI3 was added
gene: GLI3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GLI3 were set to 24736735; 15739154
Phenotypes for gene: GLI3 were set to Greig cephalopolysyndactyly syndrome (175700); Pallister-Hall syndrome (146510)
Pituitary hormone deficiency v0.0 GLI2 Seb Lunke gene: GLI2 was added
gene: GLI2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GLI2 were set to 14581620; 25878059
Phenotypes for gene: GLI2 were set to Culler-Jones syndrome (615849); Holoprosencephaly 9 (610829)
Pituitary hormone deficiency v0.0 GHSR Seb Lunke gene: GHSR was added
gene: GHSR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GHSR were set to 19789204; 25557026
Phenotypes for gene: GHSR were set to Growth hormone deficiency, isolated partial (615925)
Pituitary hormone deficiency v0.0 GHRHR Seb Lunke gene: GHRHR was added
gene: GHRHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHRHR were set to Growth hormone deficiency, isolated, type IV (618157)
Pituitary hormone deficiency v0.0 GHR Seb Lunke gene: GHR was added
gene: GHR was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Growth hormone insensitivity, partial (604271); Increased responsiveness to growth hormone (604271); Laron dwarfism (262500)
Pituitary hormone deficiency v0.0 GH1 Seb Lunke gene: GH1 was added
gene: GH1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: GH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GH1 were set to Growth hormone deficiency, isolated, type IA (262400); Growth hormone deficiency, isolated, type IB (612781); Growth hormone deficiency, isolated, type II (173100)
Pituitary hormone deficiency v0.0 FOXA2 Seb Lunke gene: FOXA2 was added
gene: FOXA2 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
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
Phenotypes for gene: FOXA2 were set to No OMIM number; Congenital hyperinsulinism; Congenital hypopituitarism
Pituitary hormone deficiency v0.0 FGFR1 Seb Lunke gene: FGFR1 was added
gene: FGFR1 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FGFR1 were set to 22319038; 25759380
Phenotypes for gene: FGFR1 were set to Jackson-Weiss syndrome (123150); Pfeiffer syndrome (101600); Hypogonadotropic hypogonadism 2 with or without anosmia (147950); Hartsfield syndrome (615465)
Pituitary hormone deficiency v0.0 FGF8 Seb Lunke gene: FGF8 was added
gene: FGF8 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FGF8 were set to 22319038; 21832120; 20463092
Phenotypes for gene: FGF8 were set to Hypogonadotropic hypogonadism 6 with or without anosmia (612702)
Pituitary hormone deficiency v0.0 CHD7 Seb Lunke gene: CHD7 was added
gene: CHD7 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CHD7 were set to Hypogonadotropic hypogonadism 5 with or without anosmia (612370); CHARGE syndrome (214800)
Pituitary hormone deficiency v0.0 BTK Seb Lunke gene: BTK was added
gene: BTK was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BTK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BTK were set to 9554752; 8013627; 7849697
Phenotypes for gene: BTK were set to Isolated growth hormone deficiency, type III, with agammaglobulinemia (307200)
Pituitary hormone deficiency v0.0 Seb Lunke Added panel Pituitary hormone deficiency
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Bryony Thompson Classified gene: PTDSS1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.160 PTDSS1 Bryony Thompson Gene: ptdss1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.159 PTDSS1 Bryony Thompson gene: PTDSS1 was added
gene: PTDSS1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: PTDSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTDSS1 were set to 24241535; 29341480; 31403251
Phenotypes for gene: PTDSS1 were set to Lenz-Majewski hyperostotic dwarfism MIM#151050
Mode of pathogenicity for gene: PTDSS1 was set to Other
Review for gene: PTDSS1 was set to GREEN
Added comment: 9 unrelated patients with cutis laxa as a prominent feature of a syndromic phenotype, with 5 different de novo (or assumed de novo) heterozygous missense mutations. Gain-of-function is the established or expected mechanism of disease for these variants.
Sources: Expert list
Differences of Sex Development v0.50 PCSK1 Crystle Lee reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562752, 23800642, 17595246, 25272002, 27187081; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.158 ATP6V1E1 Bryony Thompson Classified gene: ATP6V1E1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.158 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.157 ATP6V1E1 Bryony Thompson gene: ATP6V1E1 was added
gene: ATP6V1E1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1E1 were set to 28065471; 27023906
Phenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC MIM#617402
Review for gene: ATP6V1E1 was set to GREEN
Added comment: 3 unrelated consanguineous families from Iran, Kuwait, and Saudi Arabia, homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa, each segregating in an affected sibling. Molecular analyses of patient tissues was supportive: complexome profiling in cultured fibroblasts showed a markedly reduced abundance of the assembled V1 domain and of the complete membrane-bound V1V0 complex.
Sources: Expert list
Cutis Laxa v0.5 ATP6V1E1 Bryony Thompson changed review comment from: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular anlayses of patient tissues was supportive.
Sources: Expert list; to: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular analyses of patient tissues was supportive.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Marked gene: MAT2A as ready
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Gene: mat2a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Classified gene: MAT2A as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.156 MAT2A Bryony Thompson Gene: mat2a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.155 MAT2A Bryony Thompson gene: MAT2A was added
gene: MAT2A was added to Aortopathy_Connective Tissue Disorders. Sources: ClinGen
Mode of inheritance for gene: MAT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAT2A were set to 30071989; 25557781
Phenotypes for gene: MAT2A were set to Thoracic aortic aneurysm
Review for gene: MAT2A was set to AMBER
Added comment: PMID: 25557781 - A rare missense (p.Glu344Ala) identified in a family that segregated with thoracic aortic disease and a second missense was identified in an unrelated thoracic aortic disease proband. Morpholino KO in zebrafish lead to pericardial edema and rescue by human MAT2A
PMID: 30071989 - Classified as Limited by the HTAAD GCEP, downgraded from Moderate due to the absence of additional variants identified in a large (>400) unpublished aortopathy cohort. Categorised as uncertain, because it is a recently reported gene-disease association.
Sources: ClinGen
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Marked gene: HCN4 as ready
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Gene: hcn4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Classified gene: HCN4 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.154 HCN4 Bryony Thompson Gene: hcn4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.153 HCN4 Bryony Thompson gene: HCN4 was added
gene: HCN4 was added to Aortopathy_Connective Tissue Disorders. Sources: ClinGen
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCN4 were set to 30071989; 27173043
Phenotypes for gene: HCN4 were set to Sick sinus syndrome 2 with cardiac noncompaction and ascending aorta dilation
Review for gene: HCN4 was set to AMBER
Added comment: PMID: 27173043 - Dilation of the ascending aorta was detected in 20 of 26 (77%) HCN4 mutation-positive cases from 7 unrelated families in whom images could be obtained to assess the ascending aorta.
PMID: 30071989 - Classified as Limited by the HTAAD GCEP, downgraded from Moderate due to the absence of aortic dissection and lack of longitudinal data on aortic growth. Categorised as uncertain, because it is a recently reported gene-disease association.
Sources: ClinGen
Differences of Sex Development v0.50 PROK2 Crystle Lee reviewed gene: PROK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18559922, 17054399, 17959774, 18285834; Phenotypes: Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.50 PROP1 Crystle Lee reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15941866, 11549703; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3307 AKR1C4 Zornitza Stark Marked gene: AKR1C4 as ready
Mendeliome v0.3307 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3307 AKR1C4 Zornitza Stark Phenotypes for gene: AKR1C4 were changed from to {46XY sex reversal 8, modifier of}, MIM# 614279
Mendeliome v0.3306 AKR1C4 Zornitza Stark Publications for gene: AKR1C4 were set to
Mendeliome v0.3305 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3304 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Mendeliome v0.3304 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Mendeliome v0.3303 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Marked gene: AKR1C4 as ready
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Phenotypes for gene: AKR1C4 were changed from to {46XY sex reversal 8, modifier of}, MIM# 614279
Differences of Sex Development v0.49 AKR1C4 Zornitza Stark Publications for gene: AKR1C4 were set to
Differences of Sex Development v0.48 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Phenotypes for gene: AKR1C2 were changed from to 46XY sex reversal 8, MIM# 614279
Differences of Sex Development v0.45 AKR1C2 Zornitza Stark Publications for gene: AKR1C2 were set to
Differences of Sex Development v0.44 AKR1C2 Zornitza Stark Mode of inheritance for gene: AKR1C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Classified gene: AKR1C2 as Red List (low evidence)
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Achromatopsia v0.18 Bryony Thompson Panel status changed from internal to public
Differences of Sex Development v0.42 AKR1C2 Zornitza Stark reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: 46XY sex reversal 8, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2747 RPL10 Crystle Lee reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 26290468, 25846674, 29066376; Phenotypes: Mental retardation, X-linked, syndromic, 35 (MIM#300998); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.42 RPL10 Crystle Lee gene: RPL10 was added
gene: RPL10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPL10 were set to 25316788; 26290468; 25846674; 29066376
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Review for gene: RPL10 was set to GREEN
Added comment: At least 3 variants have been reported. Urogenital anomalies are a feature of the associated condition.

PMID: 25316788: Variant reported in 3 members of a family. Genitourinary abnormalities (ie cryptorchidism) reported in all 3 affected individuals.

PMID: 26290468: Reported in a family with two affected cousins presenting with X-linked ID, cerebellar hypoplasia, and spondylo-epiphyseal dysplasia. Only one of the affected males presented with cryptorchidism.

PMID: 25846674: 3 of 4 affected males in the family presented with urogenital anomalies
Sources: Expert Review
Differences of Sex Development v0.42 SAMD9 Crystle Lee gene: SAMD9 was added
gene: SAMD9 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9 were set to 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome (MIM#617053)
Review for gene: SAMD9 was set to GREEN
Added comment: At least 10 families ( 8 diff variants) reported in one publication. External genital abnormalities observed in all 46, XY patients.
Sources: Expert Review
Differences of Sex Development v0.42 SEMA3E Crystle Lee gene: SEMA3E was added
gene: SEMA3E was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SEMA3E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEMA3E were set to 25985275
Phenotypes for gene: SEMA3E were set to ?CHARGE syndrome (MIM#214800)
Review for gene: SEMA3E was set to RED
Added comment: Only one variant reported in 2 sibling with Kallman syndrome. Mouse model supports involvement of this gene with the phenotype. Variant not present in gnomad in homozygosity.
Sources: Expert Review
Arthrogryposis v0.186 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Arthrogryposis v0.186 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.186 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Heterotaxy, visceral, 1, X-linked, MIM# 306955; VACTERL association, X-linked, MIM# 314390
Arthrogryposis v0.185 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.184 ZIC3 Zornitza Stark Classified gene: ZIC3 as Red List (low evidence)
Arthrogryposis v0.184 ZIC3 Zornitza Stark Gene: zic3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.183 ZIC3 Zornitza Stark reviewed gene: ZIC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 1, X-linked, MIM# 306955, VACTERL association, X-linked, MIM# 314390; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.42 SGPL1 Crystle Lee gene: SGPL1 was added
gene: SGPL1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 28165339; 28165343; 28181337
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 (MIM#617575)
Review for gene: SGPL1 was set to GREEN
Added comment: >5 families reported. Cryptorchidism and hypogonadism are features of the associated phenotype.
Sources: Expert Review
Arthrogryposis v0.183 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
Arthrogryposis v0.183 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Arthrogryposis v0.183 VAMP1 Zornitza Stark Classified gene: VAMP1 as Green List (high evidence)
Arthrogryposis v0.183 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Arthrogryposis v0.182 VAMP1 Zornitza Stark gene: VAMP1 was added
gene: VAMP1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: VAMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAMP1 were set to 28253535
Phenotypes for gene: VAMP1 were set to Myasthenic syndrome, congenital, 25, MIM# 618323
Review for gene: VAMP1 was set to GREEN
Added comment: Severe neonatal hypotonia and joint laxity, though joint contractures described in some affected individuals.
Sources: Expert list
Arthrogryposis v0.181 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Arthrogryposis v0.181 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Arthrogryposis v0.181 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801
Arthrogryposis v0.180 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Arthrogryposis v0.179 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.178 UNC80 Zornitza Stark Classified gene: UNC80 as Red List (low evidence)
Arthrogryposis v0.178 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Arthrogryposis v0.177 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: RED; Mode of pathogenicity: None; Publications: 26545877, 26708753, 26708751; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.362 SOX10 Crystle Lee reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643381, 24845202; Phenotypes: PCWH syndrome (MIM#609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584), Waardenburg syndrome, type 4C (MIM#613266); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.42 SOX10 Crystle Lee gene: SOX10 was added
gene: SOX10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX10 were set to 23643381; 15004559
Phenotypes for gene: SOX10 were set to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Mode of pathogenicity for gene: SOX10 was set to Other
Review for gene: SOX10 was set to GREEN
Added comment: Well reported gene disease association. Cryptorchidism and hypogonadism is a feature of Kallman Syndrome and WS4C

PMID: 23643381: Reported 6 variants in individuals with Kallman syndrome which is associated with hypogonadotropic hypogonadism. Functional studies performed.

PMID: 15004559: PCWH is caused by dominant-negative mutations (truncating variants) whereas NMD and thus haploinsufficiency results in WS4C
Sources: Expert Review
Arthrogryposis v0.177 TTN Zornitza Stark Marked gene: TTN as ready
Arthrogryposis v0.177 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Arthrogryposis v0.177 TTN Zornitza Stark Classified gene: TTN as Green List (high evidence)
Arthrogryposis v0.177 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Differences of Sex Development v0.42 TAC3 Crystle Lee reviewed gene: TAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19079066, 20332248, 23329188, 22031817; Phenotypes: Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.176 TTN Zornitza Stark gene: TTN was added
gene: TTN was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 24105469; 31660661; 29575618; 28040389
Phenotypes for gene: TTN were set to Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10
Review for gene: TTN was set to GREEN
Added comment: By Sanger sequencing the TTN gene in 31 patients from 23 families segregating congenital core myopathy and primary heart disease, Chauveau et al. (2014) identified homozygous or compound heterozygous mutations in 5 patients from 4 families. The severity of the phenotype varied among the families. All 5 patients had congenital or infantile muscle weakness with axial and distal joint contractures and relatively preserved respiratory function. One individual presented with arthrogryposis, dislocated hips with dysplasia, and elbow, hip, and knee contractures.
Bryen et al: eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (c.39974-11T>G), inherited in trans with a second pathogenic TTN variant.
Two families with AMC and biallelic truncating mutations in 29575618; 28040389.
Sources: Expert list
Arthrogryposis v0.175 TRIP4 Zornitza Stark reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, MIM# 616866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 TOE1 Crystle Lee gene: TOE1 was added
gene: TOE1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOE1 were set to 28092684
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7 (MIM#614969)
Review for gene: TOE1 was set to GREEN
Added comment: >10 families with pontocerebellar hypoplasia type 7 (PCH7) reported with biallelic variants.MRI showed reduced cerebellar volume in these families. Ambiguous genitalia is a feature of this condition.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v0.140 TOE1 Crystle Lee reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28092684; Phenotypes: Pontocerebellar hypoplasia, type 7 (MIM#614969); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 TSPYL1 Crystle Lee reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.175 TBX22 Zornitza Stark Marked gene: TBX22 as ready
Arthrogryposis v0.175 TBX22 Zornitza Stark Gene: tbx22 has been classified as Red List (Low Evidence).
Arthrogryposis v0.175 TBX22 Zornitza Stark Phenotypes for gene: TBX22 were changed from to Cleft palate with ankyloglossia, MIM# 303400
Arthrogryposis v0.174 TBX22 Zornitza Stark Classified gene: TBX22 as Red List (low evidence)
Arthrogryposis v0.174 TBX22 Zornitza Stark Gene: tbx22 has been classified as Red List (Low Evidence).
Arthrogryposis v0.173 TBX22 Zornitza Stark reviewed gene: TBX22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleft palate with ankyloglossia, MIM# 303400; Mode of inheritance: None
Arthrogryposis v0.173 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Arthrogryposis v0.173 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Arthrogryposis v0.173 STAC3 Zornitza Stark Classified gene: STAC3 as Green List (high evidence)
Arthrogryposis v0.173 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Arthrogryposis v0.172 STAC3 Zornitza Stark gene: STAC3 was added
gene: STAC3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to 23736855; 30168660; 28777491
Phenotypes for gene: STAC3 were set to Myopathy, congenital, Baily-Bloch, MIM# 255995
Review for gene: STAC3 was set to GREEN
Added comment: Arthrogryposis is part of the phenotype.
Sources: Expert list
Arthrogryposis v0.171 SMN1 Zornitza Stark Marked gene: SMN1 as ready
Arthrogryposis v0.171 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Arthrogryposis v0.171 SMN1 Zornitza Stark Classified gene: SMN1 as Green List (high evidence)
Arthrogryposis v0.171 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Arthrogryposis v0.170 SMN1 Zornitza Stark gene: SMN1 was added
gene: SMN1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy, type 0
Review for gene: SMN1 was set to GREEN
Added comment: Most severe end of the spectrum can present with arthrogryposis.
Sources: Expert list
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Deleted their comment
Arthrogryposis v0.169 SLC9A6 Zornitza Stark commented on gene: SLC9A6: Contractures are reported but condition does not
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.169 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
Arthrogryposis v0.168 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.167 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Amber List (moderate evidence)
Arthrogryposis v0.167 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC9A6 Zornitza Stark reviewed gene: SLC9A6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Marked gene: SLC6A9 as ready
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Classified gene: SLC6A9 as Amber List (moderate evidence)
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Classified gene: SLC6A9 as Green List (high evidence)
Arthrogryposis v0.166 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Green List (High Evidence).
Arthrogryposis v0.165 SLC6A9 Zornitza Stark gene: SLC6A9 was added
gene: SLC6A9 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A9 were set to 27773429; 27481395
Phenotypes for gene: SLC6A9 were set to Glycine encephalopathy with normal serum glycine, MIM#617301; arthrogryposis
Review for gene: SLC6A9 was set to AMBER
Added comment: Two of the reported families have had arthrogryposis as a manifesting feature.
Sources: Expert list
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Classified gene: SLC18A3 as Amber List (moderate evidence)
Arthrogryposis v0.164 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.163 SLC18A3 Zornitza Stark gene: SLC18A3 was added
gene: SLC18A3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209
Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis
Review for gene: SLC18A3 was set to AMBER
Added comment: Two of four families presented with fetal akinesia and arthrogryposis.
Sources: Expert list
Arthrogryposis v0.162 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Arthrogryposis v0.162 RBM10 Zornitza Stark Gene: rbm10 has been classified as Red List (Low Evidence).
Arthrogryposis v0.162 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, MIM# 311900
Arthrogryposis v0.161 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.160 RBM10 Zornitza Stark Classified gene: RBM10 as Red List (low evidence)
Arthrogryposis v0.160 RBM10 Zornitza Stark Gene: rbm10 has been classified as Red List (Low Evidence).
Arthrogryposis v0.159 RBM10 Zornitza Stark reviewed gene: RBM10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: TARP syndrome, MIM# 311900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3303 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Mendeliome v0.3303 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3303 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from to Lethal congenital contractural syndrome 3, MIM# 611369
Mendeliome v0.3302 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to
Mendeliome v0.3301 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3300 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Mendeliome v0.3300 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.159 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from to Lethal congenital contractural syndrome 3, MIM# 611369
Arthrogryposis v0.158 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to
Arthrogryposis v0.157 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.156 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Arthrogryposis v0.156 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.155 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.155 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Arthrogryposis v0.155 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.155 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM# 300209
Arthrogryposis v0.154 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Arthrogryposis v0.153 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.152 OFD1 Zornitza Stark Classified gene: OFD1 as Red List (low evidence)
Arthrogryposis v0.152 OFD1 Zornitza Stark Gene: ofd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.151 OFD1 Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: 20301367; Phenotypes: Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200, Simpson-Golabi-Behmel syndrome, type 2, MIM# 300209; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.151 MYMK Zornitza Stark Marked gene: MYMK as ready
Arthrogryposis v0.151 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Arthrogryposis v0.151 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Arthrogryposis v0.151 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Arthrogryposis v0.150 MYMK Zornitza Stark gene: MYMK was added
gene: MYMK was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to 28681861
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome 254940
Review for gene: MYMK was set to GREEN
Added comment: Distal contractures are part of the phenotype of this muscle disorder.
Sources: Expert list
Arthrogryposis v0.149 MYL1 Zornitza Stark Marked gene: MYL1 as ready
Arthrogryposis v0.149 MYL1 Zornitza Stark Gene: myl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.149 MYL1 Zornitza Stark gene: MYL1 was added
gene: MYL1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to 30215711
Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, MIM# 618414
Review for gene: MYL1 was set to RED
Added comment: Two families and a zebrafish model. Predominant finding is that of hypotonia, mild contractures reported in one.
Sources: Expert list
Arthrogryposis v0.148 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301719; Phenotypes: MED12-related disorders; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Marked gene: MAGEL2 as ready
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Classified gene: MAGEL2 as Green List (high evidence)
Arthrogryposis v0.148 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Arthrogryposis v0.147 MAGEL2 Zornitza Stark gene: MAGEL2 was added
gene: MAGEL2 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAGEL2 were set to 24076603; 27195816; 26365340
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome
Review for gene: MAGEL2 was set to GREEN
Added comment: Fountain et al. (2017) reported 18 patients with SHFYNG ascertained on the basis of genetic studies from several different research groups or laboratories. Joint contractures were present in almost all patients, and ranged from only the interphalangeal joints to lethal fetal akinesia with severe arthrogryposis.
Mejlachowicz et al (2015) reported two unrelated families with lethal AMC and heterozygous truncating frameshift MAGEL2 mutations on paternal allele.
Sources: Expert list
Arthrogryposis v0.146 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Arthrogryposis v0.146 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Arthrogryposis v0.146 LMX1B Zornitza Stark Classified gene: LMX1B as Green List (high evidence)
Arthrogryposis v0.146 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Arthrogryposis v0.145 LMX1B Zornitza Stark gene: LMX1B was added
gene: LMX1B was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LMX1B were set to Nail-patella syndrome, MIM# 161200
Review for gene: LMX1B was set to GREEN
Added comment: Elbow and knee contractures are common features.
Sources: Expert list
Arthrogryposis v0.144 L1CAM Zornitza Stark Marked gene: L1CAM as ready
Arthrogryposis v0.144 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Arthrogryposis v0.144 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from to Hydrocephalus due to aqueductal stenosis 307000
Arthrogryposis v0.143 L1CAM Zornitza Stark Publications for gene: L1CAM were set to
Arthrogryposis v0.142 L1CAM Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.141 L1CAM Zornitza Stark Classified gene: L1CAM as Red List (low evidence)
Arthrogryposis v0.141 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Arthrogryposis v0.140 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: RED; Mode of pathogenicity: None; Publications: 31504653; Phenotypes: Hydrocephalus due to aqueductal stenosis 307000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.140 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Arthrogryposis v0.140 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.140 GPC3 Zornitza Stark Phenotypes for gene: GPC3 were changed from to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Arthrogryposis v0.139 GPC3 Zornitza Stark Publications for gene: GPC3 were set to
Arthrogryposis v0.138 GPC3 Zornitza Stark Mode of inheritance for gene: GPC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.137 GPC3 Zornitza Stark Classified gene: GPC3 as Red List (low evidence)
Arthrogryposis v0.137 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.136 GPC3 Zornitza Stark reviewed gene: GPC3: Rating: RED; Mode of pathogenicity: None; Publications: 20301398; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.136 FLNA Zornitza Stark Marked gene: FLNA as ready
Arthrogryposis v0.136 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Arthrogryposis v0.136 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to FLNA-related disorders; Otopalatodigital syndrome, type I 311300; Otopalatodigital syndrome, type II 304120; Terminal osseous dysplasia 300244
Arthrogryposis v0.135 FLNA Zornitza Stark Publications for gene: FLNA were set to
Arthrogryposis v0.134 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.134 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.133 FLNA Zornitza Stark reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26804200, 30561107, 20301567; Phenotypes: FLNA-related disorders, Otopalatodigital syndrome, type I 311300, Otopalatodigital syndrome, type II 304120, Terminal osseous dysplasia 300244; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Arthrogryposis v0.132 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Arthrogryposis v0.132 FHL1 Zornitza Stark Gene: fhl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.132 FHL1 Zornitza Stark Phenotypes for gene: FHL1 were changed from to Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696; Myopathy, X-linked, with postural muscle atrophy, MIM# 300696; Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717; Reducing body myopathy, X-linked 1b, with late childhood or adult onset, MIM# 300718; Scapuloperoneal myopathy, X-linked dominant, MIM# 300695
Arthrogryposis v0.131 FHL1 Zornitza Stark Mode of inheritance for gene: FHL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.130 FHL1 Zornitza Stark Classified gene: FHL1 as Red List (low evidence)
Arthrogryposis v0.130 FHL1 Zornitza Stark Gene: fhl1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.129 FHL1 Zornitza Stark reviewed gene: FHL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696, Myopathy, X-linked, with postural muscle atrophy, MIM# 300696, Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717, Reducing body myopathy, X-linked 1b, with late childhood or adult onset, MIM# 300718, Scapuloperoneal myopathy, X-linked dominant, MIM# 300695; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.129 FGD1 Zornitza Stark Marked gene: FGD1 as ready
Arthrogryposis v0.129 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.129 FGD1 Zornitza Stark Phenotypes for gene: FGD1 were changed from to Aarskog-Scott syndrome, MIM# 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
Arthrogryposis v0.128 FGD1 Zornitza Stark Publications for gene: FGD1 were set to
Arthrogryposis v0.127 FGD1 Zornitza Stark Mode of inheritance for gene: FGD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.126 FGD1 Zornitza Stark Classified gene: FGD1 as Red List (low evidence)
Arthrogryposis v0.126 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.125 FGD1 Zornitza Stark reviewed gene: FGD1: Rating: RED; Mode of pathogenicity: None; Publications: 27551683; Phenotypes: Aarskog-Scott syndrome, MIM# 305400, Mental retardation, X-linked syndromic 16 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.125 ERCC5 Zornitza Stark Classified gene: ERCC5 as Green List (high evidence)
Arthrogryposis v0.125 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Green List (High Evidence).
Arthrogryposis v0.124 ERCC5 Zornitza Stark edited their review of gene: ERCC5: Changed publications: 24700531, 32557569
Arthrogryposis v0.124 ERCC5 Zornitza Stark changed review comment from: Single family reported with 5 affected fetuses and severe COFS including arthrogryposis.
Sources: Expert list; to: A family reported with 5 affected fetuses and severe COFS including arthrogryposis in PMID:24700531. Further two included in a recent review of severe neonatal presentations of nucleotide excision-repair disorders (PMID:32557569).
Sources: Expert list
Arthrogryposis v0.124 ERCC5 Zornitza Stark edited their review of gene: ERCC5: Changed rating: GREEN
Arthrogryposis v0.124 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
Arthrogryposis v0.124 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.124 ERCC5 Zornitza Stark Classified gene: ERCC5 as Amber List (moderate evidence)
Arthrogryposis v0.124 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.123 ERCC5 Zornitza Stark gene: ERCC5 was added
gene: ERCC5 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC5 were set to 24700531
Phenotypes for gene: ERCC5 were set to Cerebrooculofacioskeletal syndrome 3, MIM# 616570
Review for gene: ERCC5 was set to AMBER
Added comment: Single family reported with 5 affected fetuses and severe COFS including arthrogryposis.
Sources: Expert list
Mendeliome v0.3299 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Mendeliome v0.3299 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3299 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from to Lethal congenital contractural syndrome 2, MIM# 607598
Mendeliome v0.3298 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to
Mendeliome v0.3297 ERBB3 Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3296 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Mendeliome v0.3296 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.122 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Arthrogryposis v0.122 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.122 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from to Lethal congenital contractural syndrome 2, MIM# 607598
Arthrogryposis v0.121 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to
Arthrogryposis v0.120 ERBB3 Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.119 ERBB3 Zornitza Stark Classified gene: ERBB3 as Amber List (moderate evidence)
Arthrogryposis v0.119 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.118 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.118 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, MIM# 300148
Arthrogryposis v0.117 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Arthrogryposis v0.116 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.115 EIF2S3 Zornitza Stark Classified gene: EIF2S3 as Red List (low evidence)
Arthrogryposis v0.115 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.114 EIF2S3 Zornitza Stark reviewed gene: EIF2S3: Rating: RED; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.114 EBP Zornitza Stark Publications for gene: EBP were set to 21634086
Arthrogryposis v0.113 EBP Zornitza Stark edited their review of gene: EBP: Changed publications: 21634086, 24704792
Arthrogryposis v0.113 EBP Zornitza Stark Marked gene: EBP as ready
Arthrogryposis v0.113 EBP Zornitza Stark Gene: ebp has been classified as Green List (High Evidence).
Arthrogryposis v0.113 EBP Zornitza Stark Phenotypes for gene: EBP were changed from to Chondrodysplasia punctata, X-linked dominant, MIM# 302960
Arthrogryposis v0.112 EBP Zornitza Stark Publications for gene: EBP were set to
Arthrogryposis v0.111 EBP Zornitza Stark Mode of inheritance for gene: EBP was changed from Unknown to Other
Arthrogryposis v0.110 EBP Zornitza Stark reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21634086; Phenotypes: Chondrodysplasia punctata, X-linked dominant, MIM# 302960; Mode of inheritance: Other
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Classified gene: DYNC1H1 as Green List (high evidence)
Arthrogryposis v0.110 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Arthrogryposis v0.109 DYNC1H1 Zornitza Stark gene: DYNC1H1 was added
gene: DYNC1H1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1H1 were set to 25609763; 25512093; 28554554
Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228; Mental retardation, autosomal dominant 13, MIM# 614563; Spinal muscular atrophy, lower extremity-predominant 1, MIM# 158600
Review for gene: DYNC1H1 was set to GREEN
Added comment: Phenotypes associated with DYNC1H1 range from spinal muscular atrophy (SMA), hereditary motor and sensory neuropathy (HMSN), cortical malformations, or a combination of these. Multiple families reported where arthrogryposis is a prominent feature.
Sources: Expert list
Mendeliome v0.3295 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Mendeliome v0.3295 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3295 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Mendeliome v0.3294 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Mendeliome v0.3293 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3292 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Mendeliome v0.3292 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3291 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.59 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Muscular dystrophy and myopathy_Paediatric v0.58 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Muscular dystrophy and myopathy_Paediatric v0.57 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.56 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.56 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.57 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM#615042
Congenital Disorders of Glycosylation v0.56 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Congenital Disorders of Glycosylation v0.55 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.54 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v0.54 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v0.53 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM#615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.108 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Arthrogryposis v0.108 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.108 DPM2 Zornitza Stark Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu, MIM# 615042
Arthrogryposis v0.107 DPM2 Zornitza Stark Publications for gene: DPM2 were set to
Arthrogryposis v0.106 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.105 DPM2 Zornitza Stark Classified gene: DPM2 as Amber List (moderate evidence)
Arthrogryposis v0.105 DPM2 Zornitza Stark Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.104 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Classified gene: DPAGT1 as Green List (high evidence)
Arthrogryposis v0.104 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.103 DPAGT1 Zornitza Stark gene: DPAGT1 was added
gene: DPAGT1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DPAGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPAGT1 were set to 26033833; 22786653; 30653653; 22492991
Phenotypes for gene: DPAGT1 were set to Congenital disorder of glycosylation, type Ij; Myasthenic syndrome, congenital, 13, with tubular aggregates 614750
Review for gene: DPAGT1 was set to GREEN
Added comment: Fetal akinesia and AMC.
Sources: Expert list
Arthrogryposis v0.102 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Arthrogryposis v0.102 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Arthrogryposis v0.102 DHCR24 Zornitza Stark Classified gene: DHCR24 as Green List (high evidence)
Arthrogryposis v0.102 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Arthrogryposis v0.101 DHCR24 Zornitza Stark gene: DHCR24 was added
gene: DHCR24 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR24 were set to 21671375; 12457401; 29175559; 21559050
Phenotypes for gene: DHCR24 were set to Desmosterolosis, MIM# 602398
Review for gene: DHCR24 was set to GREEN
Added comment: At least 4 families reported where contractures are a feature of the condition.
Sources: Expert list
Arthrogryposis v0.100 DCX Zornitza Stark Marked gene: DCX as ready
Arthrogryposis v0.100 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Arthrogryposis v0.100 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067
Arthrogryposis v0.99 DCX Zornitza Stark Publications for gene: DCX were set to
Arthrogryposis v0.98 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.97 DCX Zornitza Stark Classified gene: DCX as Red List (low evidence)
Arthrogryposis v0.97 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Arthrogryposis v0.96 DCX Zornitza Stark reviewed gene: DCX: Rating: RED; Mode of pathogenicity: None; Publications: 20301364; Phenotypes: Lissencephaly, X-linked, MIM# 300067; Mode of inheritance: None
Cerebellar and Pontocerebellar Hypoplasia v0.140 COASY Zornitza Stark Classified gene: COASY as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v0.140 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.96 COASY Zornitza Stark Marked gene: COASY as ready
Arthrogryposis v0.96 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.96 COASY Zornitza Stark Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v0.96 COASY Zornitza Stark Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.95 COASY Zornitza Stark gene: COASY was added
gene: COASY was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828
Phenotypes for gene: COASY were set to Pontocerebellar hypoplasia; microcephaly; arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: Two families reported with a severe, prenatal onset phenotype comprising PCH, microcephaly and arthrogryposis. Note gene is also associated with NBIA.
Sources: Expert list
Arthrogryposis v0.94 CASK Zornitza Stark Marked gene: CASK as ready
Arthrogryposis v0.94 CASK Zornitza Stark Gene: cask has been classified as Red List (Low Evidence).
Arthrogryposis v0.94 CASK Zornitza Stark Phenotypes for gene: CASK were changed from to FG syndrome 4, MIM# 300422; Mental retardation, with or without nystagmus, MIM# 300422
Arthrogryposis v0.93 CASK Zornitza Stark Publications for gene: CASK were set to
Arthrogryposis v0.92 CASK Zornitza Stark Mode of inheritance for gene: CASK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.91 CASK Zornitza Stark Classified gene: CASK as Red List (low evidence)
Arthrogryposis v0.91 CASK Zornitza Stark Gene: cask has been classified as Red List (Low Evidence).
Arthrogryposis v0.90 CASK Zornitza Stark reviewed gene: CASK: Rating: RED; Mode of pathogenicity: None; Publications: 24278995; Phenotypes: FG syndrome 4, MIM# 300422, Mental retardation, with or without nystagmus, MIM# 300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.90 ATRX Zornitza Stark Marked gene: ATRX as ready
Arthrogryposis v0.90 ATRX Zornitza Stark Gene: atrx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.90 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to Alpha-thalassemia/mental retardation syndrome, MIM# 301040
Arthrogryposis v0.89 ATRX Zornitza Stark Publications for gene: ATRX were set to
Arthrogryposis v0.88 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.87 ATRX Zornitza Stark Classified gene: ATRX as Amber List (moderate evidence)
Arthrogryposis v0.87 ATRX Zornitza Stark Gene: atrx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.86 ATRX Zornitza Stark reviewed gene: ATRX: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301622; Phenotypes: Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.86 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Green List (high evidence)
Arthrogryposis v0.86 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Arthrogryposis v0.85 ATP1A2 Zornitza Stark changed review comment from: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list; to: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Mouse model is perinatal lethal. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list
Arthrogryposis v0.85 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed rating: GREEN
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Amber List (moderate evidence)
Arthrogryposis v0.85 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.84 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 30690204
Phenotypes for gene: ATP1A2 were set to hydrops; arthrogryposis; microcephaly; malformations of cortical development; dysmorphic features; severe respiratory insufficiency
Review for gene: ATP1A2 was set to AMBER
Added comment: 3 newborns from 2 unrelated families who died neontally, presenting in utero with fetal hydrops, seizures and polyhydramnios. At birth they had arthrogryposis, microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic LOF variants in ATP1A2 were found on WES. Note mono allelic variants in this gene cause alternating hemiplegia/migraine phenotypes.
Sources: Expert list
Arthrogryposis v0.83 ATAD1 Zornitza Stark Marked gene: ATAD1 as ready
Arthrogryposis v0.83 ATAD1 Zornitza Stark Gene: atad1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.83 ATAD1 Zornitza Stark Classified gene: ATAD1 as Amber List (moderate evidence)
Arthrogryposis v0.83 ATAD1 Zornitza Stark Gene: atad1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.82 ATAD1 Zornitza Stark gene: ATAD1 was added
gene: ATAD1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD1 were set to 29659736; 29390050; 28180185
Phenotypes for gene: ATAD1 were set to Hyperekplexia 4, MIM# 618011
Review for gene: ATAD1 was set to AMBER
Added comment: At least one family where arthrogryposis was a prominent manifestation of this neurological condition.
Sources: Expert list
Arthrogryposis v0.81 ARX Zornitza Stark Marked gene: ARX as ready
Arthrogryposis v0.81 ARX Zornitza Stark Gene: arx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.81 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 308350; Hydranencephaly with abnormal genitalia 300215; Lissencephaly, X-linked 2 300215; Mental retardation, X-linked 29 and others 300419; Partington syndrome 309510; Proud syndrome 300004
Arthrogryposis v0.80 ARX Zornitza Stark Publications for gene: ARX were set to
Arthrogryposis v0.79 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.78 ARX Zornitza Stark Classified gene: ARX as Amber List (moderate evidence)
Arthrogryposis v0.78 ARX Zornitza Stark Gene: arx has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.77 ARX Zornitza Stark reviewed gene: ARX: Rating: AMBER; Mode of pathogenicity: None; Publications: 21416597; Phenotypes: Epileptic encephalopathy, early infantile, 1 308350, Hydranencephaly with abnormal genitalia 300215, Lissencephaly, X-linked 2 300215, Mental retardation, X-linked 29 and others 300419, Partington syndrome 309510, Proud syndrome 300004; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.77 AP1S2 Zornitza Stark Marked gene: AP1S2 as ready
Arthrogryposis v0.77 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.77 AP1S2 Zornitza Stark Phenotypes for gene: AP1S2 were changed from to Mental retardation, X-linked syndromic 5, MIM# 304340
Arthrogryposis v0.76 AP1S2 Zornitza Stark Publications for gene: AP1S2 were set to
Arthrogryposis v0.75 AP1S2 Zornitza Stark Mode of inheritance for gene: AP1S2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.74 AP1S2 Zornitza Stark Classified gene: AP1S2 as Red List (low evidence)
Arthrogryposis v0.74 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.73 AP1S2 Zornitza Stark reviewed gene: AP1S2: Rating: RED; Mode of pathogenicity: None; Publications: 30714330; Phenotypes: Mental retardation, X-linked syndromic 5, MIM# 304340; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis v0.73 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Arthrogryposis v0.73 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Arthrogryposis v0.73 ALG3 Zornitza Stark Classified gene: ALG3 as Green List (high evidence)
Arthrogryposis v0.73 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Arthrogryposis v0.72 ALG3 Zornitza Stark gene: ALG3 was added
gene: ALG3 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: ALG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG3 were set to 16006436; 26453362; 28742265
Phenotypes for gene: ALG3 were set to Congenital disorder of glycosylation, type Id 601110
Review for gene: ALG3 was set to GREEN
Added comment: Multiple families reported with this CDG and contractures.
Sources: Expert list
Mendeliome v0.3291 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 C17orf62 Zornitza Stark Tag new gene name tag was added to gene: C17orf62.
Mendeliome v0.3290 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Phagocyte Defects v0.38 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Phagocyte Defects v0.37 C17orf62 Zornitza Stark Tag new gene name tag was added to gene: C17orf62.
Phagocyte Defects v0.37 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Cataract v0.222 ITPA Zornitza Stark Marked gene: ITPA as ready
Cataract v0.222 ITPA Zornitza Stark Gene: itpa has been classified as Amber List (Moderate Evidence).
Cataract v0.222 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Epileptic encephalopathy, early infantile, 35, MIM# 616647
Cataract v0.221 ITPA Zornitza Stark Publications for gene: ITPA were set to
Cataract v0.220 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.219 ITPA Zornitza Stark Classified gene: ITPA as Amber List (moderate evidence)
Cataract v0.219 ITPA Zornitza Stark Gene: itpa has been classified as Amber List (Moderate Evidence).
Cataract v0.218 ITPA Zornitza Stark reviewed gene: ITPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 26224535, 30816001; Phenotypes: Epileptic encephalopathy, early infantile, 35, MIM# 616647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.745 Zornitza Stark removed gene:NAXD from the panel
Leukodystrophy v0.170 NAXD Zornitza Stark Marked gene: NAXD as ready
Leukodystrophy v0.170 NAXD Zornitza Stark Gene: naxd has been classified as Green List (High Evidence).
Leukodystrophy v0.170 NAXD Zornitza Stark Classified gene: NAXD as Green List (high evidence)
Leukodystrophy v0.170 NAXD Zornitza Stark Gene: naxd has been classified as Green List (High Evidence).
Leukodystrophy v0.169 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 32462209
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, 618321
Review for gene: NAXD was set to GREEN
Added comment: Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy; another with progressive encephalopathy with brain oedema.
Sources: Expert list
Genetic Epilepsy v0.744 NAXD Elena Savva gene: NAXD was added
gene: NAXD was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to PMID: 32462209
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, 618321
Review for gene: NAXD was set to GREEN
Added comment: Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy

Patient reported with progressive encephalopathy with brain edema
Sources: Literature
Mendeliome v0.3290 DYSF Zornitza Stark Marked gene: DYSF as ready
Mendeliome v0.3290 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Mendeliome v0.3290 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Mendeliome v0.3289 DYSF Zornitza Stark Publications for gene: DYSF were set to
Mendeliome v0.3288 DYSF Zornitza Stark Mode of inheritance for gene: DYSF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3287 NEB Zornitza Stark Marked gene: NEB as ready
Mendeliome v0.3287 NEB Zornitza Stark Gene: neb has been classified as Green List (High Evidence).
Mendeliome v0.3287 NEB Zornitza Stark Phenotypes for gene: NEB were changed from to Nemaline myopathy 2, autosomal recessive 256030
Mendeliome v0.3286 NEB Zornitza Stark Publications for gene: NEB were set to
Mendeliome v0.3285 NEB Zornitza Stark Mode of inheritance for gene: NEB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, MIM# 617664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark Marked gene: MRPS34 as ready
Mendeliome v0.3284 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Green List (High Evidence).
Mendeliome v0.3284 MRPS34 Zornitza Stark Phenotypes for gene: MRPS34 were changed from to Combined oxidative phosphorylation deficiency 32, 61766
Mendeliome v0.3283 MRPS34 Zornitza Stark Publications for gene: MRPS34 were set to
Mendeliome v0.3282 MRPS34 Zornitza Stark Mode of inheritance for gene: MRPS34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 MRPS34 Elena Savva reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, 61766; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 NEB Elena Savva reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25205138; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 DYSF Elena Savva reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27602406; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Marked gene: HS6ST1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Gene: hs6st1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Classified gene: HS6ST1 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.29 HS6ST1 Bryony Thompson Gene: hs6st1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Marked gene: HARS2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Gene: hars2 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.28 HARS2 Bryony Thompson Phenotypes for gene: HARS2 were changed from ?Perrault syndrome 2 614926 to Perrault syndrome 2 614926
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.27 HARS2 Bryony Thompson Publications for gene: HARS2 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Marked gene: GNRHR as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Gene: gnrhr has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.26 GNRHR Bryony Thompson Publications for gene: GNRHR were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Marked gene: GNRH1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Gene: gnrh1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.25 GNRH1 Bryony Thompson Phenotypes for gene: GNRH1 were changed from ?Hypogonadotropic hypogonadism 12 with or without anosmia 614841 to Hypogonadotropic hypogonadism 12 with or without anosmia 614841
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.24 GNRH1 Bryony Thompson Publications for gene: GNRH1 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Marked gene: FLRT3 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Gene: flrt3 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.23 FLRT3 Bryony Thompson Publications for gene: FLRT3 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.22 FLRT3 Bryony Thompson Classified gene: FLRT3 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.22 FLRT3 Bryony Thompson Gene: flrt3 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Marked gene: IL17RD as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Gene: il17rd has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Classified gene: IL17RD as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.21 IL17RD Bryony Thompson Gene: il17rd has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.20 IL17RD Bryony Thompson Publications for gene: IL17RD were set to
Cataract v0.218 LCAT Zornitza Stark Classified gene: LCAT as Amber List (moderate evidence)
Cataract v0.218 LCAT Zornitza Stark Gene: lcat has been classified as Amber List (Moderate Evidence).
Cataract v0.217 LMX1B Zornitza Stark Classified gene: LMX1B as Amber List (moderate evidence)
Cataract v0.217 LMX1B Zornitza Stark Gene: lmx1b has been classified as Amber List (Moderate Evidence).
Cataract v0.216 LMX1B Zornitza Stark changed review comment from: Cataract is a feature of nail-patella syndrome.; to: Cataract is a reported feature of nail-patella syndrome but the typical finding is that of glaucoma.
Cataract v0.216 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed rating: AMBER
Cataract v0.216 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Cataract v0.216 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Cataract v0.216 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome, MIM# 161200
Cataract v0.215 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.214 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome, MIM# 161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.214 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Cataract v0.214 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Cataract v0.214 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from to SHORT syndrome, MIM# 269880
Cataract v0.213 PIK3R1 Zornitza Stark Mode of inheritance for gene: PIK3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.212 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Amber List (moderate evidence)
Cataract v0.212 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Amber List (Moderate Evidence).
Cataract v0.211 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: SHORT syndrome, MIM# 269880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.211 GJA1 Zornitza Stark Marked gene: GJA1 as ready
Cataract v0.211 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Cataract v0.211 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from to Oculodentodigital dysplasia, autosomal recessive, MIM# 257850
Cataract v0.210 GJA1 Zornitza Stark Mode of inheritance for gene: GJA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.209 GJA1 Zornitza Stark Classified gene: GJA1 as Red List (low evidence)
Cataract v0.209 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Cataract v0.208 GJA1 Zornitza Stark reviewed gene: GJA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculodentodigital dysplasia, autosomal recessive, MIM# 257850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.208 LCAT Zornitza Stark Marked gene: LCAT as ready
Cataract v0.208 LCAT Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap.
Cataract v0.208 LCAT Zornitza Stark Gene: lcat has been classified as Red List (Low Evidence).
Cataract v0.208 LCAT Zornitza Stark Classified gene: LCAT as Red List (low evidence)
Cataract v0.208 LCAT Zornitza Stark Gene: lcat has been classified as Red List (Low Evidence).
Cataract v0.207 ISPD Zornitza Stark reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 MIM#614643; Mode of inheritance: None
Differences of Sex Development v0.42 WNT4 Zornitza Stark Marked gene: WNT4 as ready
Differences of Sex Development v0.42 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.42 WNT4 Zornitza Stark Phenotypes for gene: WNT4 were changed from to Mullerian aplasia and hyperandrogenism (MIM#158330)
Differences of Sex Development v0.41 WNT4 Zornitza Stark Publications for gene: WNT4 were set to
Differences of Sex Development v0.40 WNT4 Zornitza Stark Mode of inheritance for gene: WNT4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.39 WNT4 Zornitza Stark Classified gene: WNT4 as Amber List (moderate evidence)
Differences of Sex Development v0.39 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark reviewed gene: ZFPM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Phenotypes for gene: ZFPM2 were changed from to 46XY sex reversal 9 (MIM#616067)
Differences of Sex Development v0.37 ZFPM2 Zornitza Stark Publications for gene: ZFPM2 were set to
Differences of Sex Development v0.36 ZFPM2 Zornitza Stark Mode of inheritance for gene: ZFPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Classified gene: ZFPM2 as Red List (low evidence)
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 ZFPM2 Zornitza Stark Tag refuted tag was added to gene: ZFPM2.
Aortopathy_Connective Tissue Disorders v0.150 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.150 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.149 ATP6V1A Zornitza Stark reviewed gene: ATP6V1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28065471; Phenotypes: Cutis laxa, autosomal recessive, type IID, MIM# 617403; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.149 PYCR1 Zornitza Stark Phenotypes for gene: PYCR1 were changed from to Cutis laxa, autosomal recessive, type IIB, MIM# 612940; Cutis laxa, autosomal recessive, type IIIB, MIM# 614438
Aortopathy_Connective Tissue Disorders v0.148 PYCR1 Zornitza Stark Classified gene: PYCR1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.148 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Cataract v0.207 LCAT Dean Phelan gene: LCAT was added
gene: LCAT was added to Cataract. Sources: Literature
Mode of inheritance for gene: LCAT was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: LCAT was set to RED
Added comment: OMIM:
Norum disease (AR) - Corneal lipid deposits, Corneal opacities
Fish-eye disease (AR) - Corneal opacities

Discussion with ZS - Corneal opacities not the same as cataracts and often misdiagnosed. Therefore leave as Red at this stage.
Sources: Literature
Cataract v0.207 ISPD Seb Lunke Marked gene: ISPD as ready
Cataract v0.207 ISPD Seb Lunke Gene: ispd has been classified as Green List (High Evidence).
Cataract v0.207 ISPD Seb Lunke Classified gene: ISPD as Green List (high evidence)
Cataract v0.207 ISPD Seb Lunke Gene: ispd has been classified as Green List (High Evidence).
Cataract v0.206 ISPD Seb Lunke gene: ISPD was added
gene: ISPD was added to Cataract. Sources: Literature
Mode of inheritance for gene: ISPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISPD were set to 22522421; 22522420
Phenotypes for gene: ISPD were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 MIM#614643
Added comment: >10 independent patients with congential cataract as part of muscular dystrophy presentation, plus functional studies in zebra fish.
Sources: Literature
Cataract v0.205 GFER Seb Lunke Marked gene: GFER as ready
Cataract v0.205 GFER Seb Lunke Gene: gfer has been classified as Green List (High Evidence).
Cataract v0.205 GFER Seb Lunke Publications for gene: GFER were set to 19409522; 25269795
Cataract v0.204 GFER Seb Lunke Classified gene: GFER as Green List (high evidence)
Cataract v0.204 GFER Seb Lunke Gene: gfer has been classified as Green List (High Evidence).
Cataract v0.203 GTF2H5 Zornitza Stark Marked gene: GTF2H5 as ready
Cataract v0.203 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Cataract v0.203 GTF2H5 Zornitza Stark Classified gene: GTF2H5 as Green List (high evidence)
Cataract v0.203 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Cataract v0.202 LONP1 Zornitza Stark Marked gene: LONP1 as ready
Cataract v0.202 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Cataract v0.202 LONP1 Zornitza Stark Classified gene: LONP1 as Green List (high evidence)
Cataract v0.202 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Cataract v0.201 GFER Paul De Fazio changed review comment from: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families.; to: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families (PMID: 28155230).
Cataract v0.201 GFER Paul De Fazio edited their review of gene: GFER: Added comment: Additional paper in 2017 brings the total count up to 8 cases from 4 unrelated families.; Changed rating: GREEN; Changed publications: 19409522, 25269795,28155230
Cataract v0.201 GTF2H5 Ain Roesley edited their review of gene: GTF2H5: Changed publications: 15220921, 24986372
Cataract v0.201 LONP1 Naomi Baker changed review comment from: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of pateints with infantile cataract identified a biallelic LONP1 mutation in patient with stand-alone cataract (PMID: 29408517).
Sources: Literature; to: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of patients with infantile cataract identified a biallelic LONP1 mutation in a patient who was otherwise healthy (PMID: 29408517).
Sources: Literature
Cataract v0.201 GTF2H5 Ain Roesley gene: GTF2H5 was added
gene: GTF2H5 was added to Cataract. Sources: Literature
Mode of inheritance for gene: GTF2H5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF2H5 were set to 15220921,24986372
Phenotypes for gene: GTF2H5 were set to Trichothiodystrophy 3, photosensitive (MIM# 616395)
Penetrance for gene: GTF2H5 were set to unknown
Review for gene: GTF2H5 was set to GREEN
Added comment: PMID: 24986372;
A 5‐year‐old male, born as a collodion baby from healthy non‐consanguineous parents, exhibited sun sensitivity, brittle hair, ichthyosis, cataracts and mental/physical retardation. He demonstrated neither neurological abnormalities nor pigmentary changes following sun exposure. Homozygous for a nonsense variant.

PMID: 15220921;
2 out of 4 patients have cataracts. The 2 patients without cataracts are siblings. (2x homs for PTVs, 1x chet for PTV and missense)
Sources: Literature
Cataract v0.201 LONP1 Naomi Baker gene: LONP1 was added
gene: LONP1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: LONP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LONP1 were set to PMID: 25574826; 29408517.
Phenotypes for gene: LONP1 were set to CODAS syndrome MIM# 600373
Penetrance for gene: LONP1 were set to Complete
Review for gene: LONP1 was set to GREEN
Added comment: Cataract is a common feature of CODAS (cerebral, ocular, dental, auricular, and skeletal anomalies) syndrome, which results from biallelic LONP1 mutations. One review of pateints with infantile cataract identified a biallelic LONP1 mutation in patient with stand-alone cataract (PMID: 29408517).
Sources: Literature
Cataract v0.201 GFER Paul De Fazio changed review comment from: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature; to: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature
Cataract v0.201 GEMIN4 Seb Lunke edited their review of gene: GEMIN4: Changed rating: AMBER; Changed phenotypes: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Cataract v0.201 GFER Paul De Fazio gene: GFER was added
gene: GFER was added to Cataract. Sources: Literature
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 19409522; 25269795
Phenotypes for gene: GFER were set to Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay MIM#613076
Review for gene: GFER was set to AMBER
gene: GFER was marked as current diagnostic
Added comment: One family (3 sibs born to healthy consang parents) described with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay had a homozygous missense variant (PMID:19409522).

Studies of patient fibroblasts and muscle tissue showed: a reduction in complex I, II, and IV activity; a lower cysteine-rich protein content; abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and accelerated time-dependent accumulation of multiple mtDNA deletions. Additional functional studies in yeast also showed mitochondrial defects.
Sources: Literature
Mendeliome v0.3281 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412; Cataract
Intellectual disability syndromic and non-syndromic v0.2747 GLS Zornitza Stark Mode of pathogenicity for gene: GLS was changed from None to Other
Mendeliome v0.3280 GLS Zornitza Stark Publications for gene: GLS were set to 30575854; 30970188
Mendeliome v0.3279 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Added comment: In addition, single individual also reported with de novo, GoF variant with profound ID, cataract.; Changed publications: 30575854, 30970188, 30239721
Intellectual disability syndromic and non-syndromic v0.2746 GLS Zornitza Stark Publications for gene: GLS were set to 30970188
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412, Catarct; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 GLS Zornitza Stark edited their review of gene: GLS: Added comment: Another three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels (PMID: 30575854).; Changed rating: GREEN; Changed publications: 30970188, 30239721, 30575854; Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Cataract v0.201 GLS Zornitza Stark Marked gene: GLS as ready
Cataract v0.201 GLS Zornitza Stark Gene: gls has been classified as Amber List (Moderate Evidence).
Cataract v0.201 GLS Zornitza Stark Classified gene: GLS as Amber List (moderate evidence)
Cataract v0.201 GLS Zornitza Stark Gene: gls has been classified as Amber List (Moderate Evidence).
Cataract v0.200 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Cataract. Sources: Expert list
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30239721
Phenotypes for gene: GLS were set to Infantile cataracts
Review for gene: GLS was set to AMBER
Added comment: Single family and a zebrafish model.
Sources: Expert list
Cataract v0.199 GEMIN4 Seb Lunke Marked gene: GEMIN4 as ready
Cataract v0.199 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Amber List (Moderate Evidence).
Cataract v0.199 GEMIN4 Seb Lunke Classified gene: GEMIN4 as Amber List (moderate evidence)
Cataract v0.199 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Amber List (Moderate Evidence).
Cataract v0.198 GEMIN4 Seb Lunke Marked gene: GEMIN4 as ready
Cataract v0.198 GEMIN4 Seb Lunke Added comment: Comment when marking as ready: 5 individuals from 3 consanguineous families reported originally; same homozygous missense in all. Another individual reported with different variant as part of a study reporting large number of novel/emerging genes in consanguineous cohort.
Cataract v0.198 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Green List (High Evidence).
Cataract v0.198 GEMIN4 Seb Lunke Classified gene: GEMIN4 as Green List (high evidence)
Cataract v0.198 GEMIN4 Seb Lunke Gene: gemin4 has been classified as Green List (High Evidence).
Cataract v0.197 GEMIN4 Seb Lunke gene: GEMIN4 was added
gene: GEMIN4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: GEMIN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN4 were set to 25558065; 27878435
Phenotypes for gene: GEMIN4 were set to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, 617913
Review for gene: GEMIN4 was set to GREEN
Added comment: From GEL: PMID: 25558065 reported on 5 affected patients from 3 unrelated consanguineous Saudi families with neurodevelopmental disorder, microcephaly cataracts and renal abnormalities. PMID: 27878435 reported on a different family with a different variant that was previously reported. The same paper also performed mouse studies and found that the gene is down regulated in key gene knockout mice with lens defects.
Sources: Literature
Cataract v0.196 NHS Zornitza Stark Marked gene: NHS as ready
Cataract v0.196 NHS Zornitza Stark Gene: nhs has been classified as Green List (High Evidence).
Cataract v0.196 NHS Zornitza Stark Phenotypes for gene: NHS were changed from to Nance-Horan syndrome (MIM# 302350)
Cataract v0.195 NHS Zornitza Stark Publications for gene: NHS were set to
Cataract v0.194 NHS Zornitza Stark Mode of inheritance for gene: NHS was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cataract v0.193 NF2 Zornitza Stark Marked gene: NF2 as ready
Cataract v0.193 NF2 Zornitza Stark Gene: nf2 has been classified as Green List (High Evidence).
Cataract v0.193 NF2 Zornitza Stark Phenotypes for gene: NF2 were changed from to Neurofibromatosis, type 2 (MIM# 101000)
Cataract v0.192 NF2 Zornitza Stark Mode of inheritance for gene: NF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.191 NDP Ain Roesley changed review comment from: Classified as "definitive" for Norrie Disease by ClinGen working group (https://search.clinicalgenome.org/kb/gene-validity/9611); to: Classified as "definitive" for Norrie Disease by ClinGen working group (https://search.clinicalgenome.org/kb/gene-validity/9611)

Progressive cataract is a feature of Norrie Disease (Genereviews, OMIM)
Cataract v0.191 NDP Zornitza Stark Marked gene: NDP as ready
Cataract v0.191 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Cataract v0.191 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Norrie disease (MIM# 310600)
Cataract v0.190 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cataract v0.189 FKTN Zornitza Stark Marked gene: FKTN as ready
Cataract v0.189 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cataract v0.189 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Limb Girdle Muscular Dystrophy with No Mental Retardation; Congenital Cataract
Cataract v0.188 FKTN Zornitza Stark Publications for gene: FKTN were set to
Cataract v0.187 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.186 FKTN Zornitza Stark Classified gene: FKTN as Amber List (moderate evidence)
Cataract v0.186 FKTN Zornitza Stark Gene: fktn has been classified as Amber List (Moderate Evidence).
Cataract v0.185 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Cataract v0.185 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Cataract v0.185 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Marfan syndrome, MIM# 154700; Weill-Marchesani syndrome 2, dominant, MIM# 608328
Cataract v0.184 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.183 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Cataract v0.183 ESCO2 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.147 PYCR1 Dean Phelan gene: PYCR1 was added
gene: PYCR1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to PMID: 19648921; 4076251; 22052856; 19576563; 19648921; 9648921; 22052856; 28294978; 27756598
Review for gene: PYCR1 was set to GREEN
gene: PYCR1 was marked as current diagnostic
Added comment: Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Sources: Literature
Cataract v0.183 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Cataract v0.183 ESCO2 Zornitza Stark Classified gene: ESCO2 as Amber List (moderate evidence)
Cataract v0.183 ESCO2 Zornitza Stark Gene: esco2 has been classified as Amber List (Moderate Evidence).
Cataract v0.182 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Cataract v0.182 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Cataract v0.182 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination (MIM# 617393)
Cataract v0.181 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3278 PYCR1 Dean Phelan changed review comment from: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.; to: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Mendeliome v0.3278 PYCR1 Seb Lunke Marked gene: PYCR1 as ready
Mendeliome v0.3278 PYCR1 Seb Lunke Gene: pycr1 has been classified as Green List (High Evidence).
Mendeliome v0.3278 PYCR1 Seb Lunke Phenotypes for gene: PYCR1 were changed from to cutis laxa
Mendeliome v0.3277 PYCR1 Seb Lunke Added comment: Comment on publications: 19648921; 4076251; 22052856; 19576563; 19648921; 9648921; 22052856; 28294978; 27756598
Mendeliome v0.3277 PYCR1 Seb Lunke Publications for gene: PYCR1 were set to
Differences of Sex Development v0.34 WNT4 Crystle Lee reviewed gene: WNT4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22503279, 21377155, 16959810; Phenotypes: Mullerian aplasia and hyperandrogenism (MIM#158330); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3276 PYCR1 Seb Lunke Mode of inheritance for gene: PYCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.147 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Classified gene: RIN2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.146 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A2 Seb Lunke Marked gene: COL6A2 as ready
Aortopathy_Connective Tissue Disorders v0.145 COL6A2 Seb Lunke Gene: col6a2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Marked gene: COL6A3 as ready
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Classified gene: COL6A3 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.145 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.144 COL6A2 Seb Lunke Classified gene: COL6A2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.144 COL6A2 Seb Lunke Gene: col6a2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.143 COL6A3 Zornitza Stark reviewed gene: COL6A3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.143 COL6A2 Seb Lunke reviewed gene: COL6A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Marked gene: LTBP4 as ready
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Classified gene: LTBP4 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.143 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Marked gene: GORAB as ready
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Gene: gorab has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Classified gene: GORAB as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.142 GORAB Zornitza Stark Gene: gorab has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Marked gene: COL6A1 as ready
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Classified gene: COL6A1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.141 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.140 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Marked gene: ATP6V1A as ready
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.140 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Green List (High Evidence).
Cataract v0.180 NHS Ain Roesley reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31755796; Phenotypes: Nance-Horan syndrome (MIM# 302350); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cataract v0.180 NF2 Ain Roesley reviewed gene: NF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurofibromatosis, type 2 (MIM# 101000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.34 ZFPM2 Crystle Lee reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24549039, 27899157, 31962012, 12223418; Phenotypes: 46XY sex reversal 9 (MIM#616067); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cataract v0.180 NDP Ain Roesley reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease (MIM# 310600); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cataract v0.180 FKTN Seb Lunke reviewed gene: FKTN: Rating: AMBER; Mode of pathogenicity: None; Publications: 18177472, 17878207; Phenotypes: Limb Girdle Muscular Dystrophy with No Mental Retardation, Congenital Cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.180 FKRP Seb Lunke reviewed gene: FKRP: Rating: AMBER; Mode of pathogenicity: None; Publications: 26833294; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.180 FBN1 Seb Lunke reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.180 ESCO2 Seb Lunke gene: ESCO2 was added
gene: ESCO2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 19574259
Phenotypes for gene: ESCO2 were set to Craniofacial abnormalities; Developmental Delay; Corneal opacities; Growth retardation; Limb abnormalities; Roberts syndrome 238300
Review for gene: ESCO2 was set to AMBER
Added comment: Corneal opacities described in 13/36 cases with Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Intellectual disability syndromic and non-syndromic v0.2743 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.744 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Genetic Epilepsy v0.743 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Genetic Epilepsy v0.742 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.741 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Marked gene: PIGY as ready
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Intellectual disability syndromic and non-syndromic v0.2740 PIGY Zornitza Stark Publications for gene: PIGY were set to
Intellectual disability syndromic and non-syndromic v0.2739 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Marked gene: PIGY as ready
Mendeliome v0.3275 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3275 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Mendeliome v0.3274 PIGY Zornitza Stark Publications for gene: PIGY were set to
Mendeliome v0.3273 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3272 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Mendeliome v0.3272 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Classified gene: MYBPC3 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.55 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Red List (Low Evidence).
Cataract v0.179 NACC1 Ain Roesley reviewed gene: NACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination (MIM# 617393); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3271 MTMR14 Zornitza Stark Marked gene: MTMR14 as ready
Mendeliome v0.3271 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models; postulated to be a modifier in the other family.
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3271 MTMR14 Zornitza Stark Classified gene: MTMR14 as Amber List (moderate evidence)
Mendeliome v0.3271 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3270 MTMR14 Zornitza Stark Deleted their comment
Mendeliome v0.3270 MTMR14 Zornitza Stark Marked gene: MTMR14 as ready
Mendeliome v0.3270 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Postulated to be a modifier.
Mendeliome v0.3270 MTMR14 Zornitza Stark Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.3270 MTMR14 Zornitza Stark Publications for gene: MTMR14 were set to
Mendeliome v0.3269 MTMR14 Zornitza Stark Mode of inheritance for gene: MTMR14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.179 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from leukodystrophy; congenital cataracts to leukodystrophy; congenital cataracts; Leukoencephalopathy with vanishing white matter, MIM# 603896
Cataract v0.178 EIF2B2 Zornitza Stark reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy with vanishing white matter, MIM# 603896; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3268 P4HA1 Zornitza Stark Marked gene: P4HA1 as ready
Mendeliome v0.3268 P4HA1 Zornitza Stark Gene: p4ha1 has been classified as Red List (Low Evidence).
Mendeliome v0.3268 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark Marked gene: P4HA1 as ready
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark Gene: p4ha1 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.139 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England EDS panel because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome. I have left it amber as I'm not sure if the overlap is sufficient for this panel.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio changed review comment from: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.
Sources: Literature; to: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.

From OMIM: "Geroderma osteodysplasticum (GO) is an autosomal recessive disorder characterized by skin wrinkling limited to the dorsa of hands and feet and to the abdomen, bowed long bones, and osteopenia with frequent fractures. There is a distinctive facial appearance with droopy skin at the cheeks, maxillary hypoplasia, and large ears. Adult patients appear prematurely aged"
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene although the authors note that their sequencing strategy would not have been able to detect some indels including single-exon deletions.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). This is the only literature supporting this gene-disease association. One other proband with MWS did not have a variant in this gene.

The same study reported that another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2737 PLCB1 Crystle Lee reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio edited their review of gene: PIEZO2: Changed publications: 24726473, 27375131
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio changed review comment from: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature; to: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome) (PMID: 27375131). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Genetic Epilepsy v0.741 PLCB1 Crystle Lee reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.138 PIEZO2 Paul De Fazio gene: PIEZO2 was added
gene: PIEZO2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PIEZO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO2 were set to 24726473
Phenotypes for gene: PIEZO2 were set to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145)
Review for gene: PIEZO2 was set to AMBER
gene: PIEZO2 was marked as current diagnostic
Added comment: 1 individual diagnosed with Marden-Walker syndrome was described with a de novo missense variant in this gene (PMID: 24726473). Another 10 families/individuals with Gordon syndrome (distal arthrogryposis type 3) and 24 with distal atrogryposis type 5 had variants in this gene. The authors posit that these three conditions represent a spectrum of disease.

Marden-Walker syndrome is described as a connective tissue disorder (https://rarediseases.info.nih.gov/diseases/6973/marden-walker-syndrome) and has significant overlap with other multi-system congenital contracture syndromes including D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome). GEL has this gene as Amber in the EDS panel noting some overlap with Kyphoscoliotic EDS in terms of scoliosis.
Sources: Literature
Mendeliome v0.3267 ROBO3 Ain Roesley reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15105459, 32373565; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 PIGY Elena Savva reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.54 MYBPC3 Elena Savva gene: MYBPC3 was added
gene: MYBPC3 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: MYBPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC3 were set to PMID: 19858127
Phenotypes for gene: MYBPC3 were set to Cardiomyopathy with myopathy
Review for gene: MYBPC3 was set to RED
Added comment: Single report of a dystrophy, patient was homozygous for a PTC.
Sources: Expert list
Mendeliome v0.3267 PYCR1 Dean Phelan reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19648921, 4076251, 22052856, 19576563, 19648921, 9648921, 22052856, 28294978, 27756598; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.362 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.361 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Deafness. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Mendeliome v0.3267 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3267 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Mendeliome v0.3267 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Mendeliome v0.3266 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Marked gene: GGPS1 as ready
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Classified gene: GGPS1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.54 GGPS1 Zornitza Stark Gene: ggps1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.53 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 RIN2 Ain Roesley gene: RIN2 was added
gene: RIN2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: RIN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIN2 were set to 19631308; 20424861; 23963297; 24449201
Phenotypes for gene: RIN2 were set to Macrocephaly, alopecia, cutis laxa, and scoliosis (MIM# 613075)
Penetrance for gene: RIN2 were set to unknown
Review for gene: RIN2 was set to GREEN
Added comment: Also known as MACS syndrome. The most striking clinical features include macrocephaly, progressive facial coarsening, gingival hypertrophy, severe scoliosis, sparse hair and skin and joint hyperlaxity. All families reported thus far are homozygous for PTVs

PMID: 19631308; 1x large consanguineous kindred with 3 affecteds

PMID: 20424861; 1x consanguineous Algerian family with three affected siblings.

PMID: 23963297; 1x patient with MACS syndrome and an additional phenotype of periventricular cystic lesions

PMID: 24449201; 2 sibs born to non-consanguineous Turkish parents exhibiting additional clinical features of bronchiectasis and hypergonadotropic hypogonadism.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 LTBP4 Ain Roesley edited their review of gene: LTBP4: Changed publications: 22829427; Changed phenotypes: Cutis laxa, autosomal recessive, type IC (MIM# 613177)
Aortopathy_Connective Tissue Disorders v0.138 ATP6V1A Ain Roesley edited their review of gene: ATP6V1A: Changed publications: 28065471
Aortopathy_Connective Tissue Disorders v0.138 COL6A3 Naomi Baker gene: COL6A3 was added
gene: COL6A3 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A3 were set to PMID: 29277723; 24443028.
Phenotypes for gene: COL6A3 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A3 were set to Complete
Mode of pathogenicity for gene: COL6A3 was set to Other
Review for gene: COL6A3 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 COL6A2 Naomi Baker gene: COL6A2 was added
gene: COL6A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A2 were set to (PMID: 29277723; 24443028)
Phenotypes for gene: COL6A2 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A2 were set to Complete
Mode of pathogenicity for gene: COL6A2 was set to Other
Review for gene: COL6A2 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 LTBP4 Ain Roesley gene: LTBP4 was added
gene: LTBP4 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: LTBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP4 were set to PMID: 22829427
Phenotypes for gene: LTBP4 were set to Cutis laxa, autosomal recessive, type IC (MIM# 613177)
Penetrance for gene: LTBP4 were set to unknown
Review for gene: LTBP4 was set to GREEN
Added comment: PMID: 22829427;
- 9 families with cutis laxa, either homozygotes or cHets.
- all PTVs except 1 homozygous missense
- Most LTBP4 mutation positive patients (11/13) had generalized moderate to severe cutis laxa, skin was hyperextensible, or appeared translucent with a prominent venous pattern (3/9), few patients had thin and slowly growing hair and inguinal and diaphragmatic hernias (5/9)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 GORAB Paul De Fazio gene: GORAB was added
gene: GORAB was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: GORAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GORAB were set to 18997784; 19681135
Phenotypes for gene: GORAB were set to Geroderma osteodysplasticum MIM#231070
Review for gene: GORAB was set to AMBER
gene: GORAB was marked as current diagnostic
Added comment: 13 families described with biallelic LoF variants (PMID: 18997784). Phenotypes included wrinkly skin and osteoporosis.

One more individual described with a homozygous missense variant (PMID: 19681135). Clinical diagnosis of GO was based on the presence of typical facial features, reduced skin elasticity, and decreased bone density.

There have been no clinical reports since 2009.

This gene is Green in PanelApp England because it has phenotypic overlap with Eherls Danlos syndrome.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 COL6A1 Naomi Baker gene: COL6A1 was added
gene: COL6A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL6A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL6A1 were set to PMID: 29277723; 24443028.
Phenotypes for gene: COL6A1 were set to Bethlem myopathy 1 MIM #158810; Ullrich congenital muscular dystrophy 1 MIM #254090
Penetrance for gene: COL6A1 were set to Complete
Mode of pathogenicity for gene: COL6A1 was set to Other
Review for gene: COL6A1 was set to GREEN
Added comment: Both loss-of-function and dominant negative mechanism has been reported for this gene. Mutations result in a spectrum of disease, ranging from the milder Bethlem myopathy (monoallelic) to the more severe Ullrich congenital muscular dystrophy (biallelic) (PMID: 29277723; 24443028).
Sources: Literature
Cataract v0.178 EIF2B2 Seb Lunke Marked gene: EIF2B2 as ready
Cataract v0.178 EIF2B2 Seb Lunke Gene: eif2b2 has been classified as Green List (High Evidence).
Cataract v0.178 EIF2B2 Seb Lunke Classified gene: EIF2B2 as Green List (high evidence)
Cataract v0.178 EIF2B2 Seb Lunke Gene: eif2b2 has been classified as Green List (High Evidence).
Mendeliome v0.3265 MTMR14 Elena Savva reviewed gene: MTMR14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20400459, 20817957, 19465920, 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of}, MIM# 160150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cataract v0.177 EIF2B2 Seb Lunke gene: EIF2B2 was added
gene: EIF2B2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B2 were set to 21484434; 14566705; 28041799
Phenotypes for gene: EIF2B2 were set to leukodystrophy; congenital cataracts
gene: EIF2B2 was marked as current diagnostic
Added comment: From GEL: There are 3 unrelated cases (PMID: 21484434; 14566705; 28041799) of patients with leukodystrophy vanishing white matter who also have congenital cataracts with different homozygous or compound heterozygous variants in this gene.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 ATP6V1A Ain Roesley gene: ATP6V1A was added
gene: ATP6V1A was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to PMID: 28065471
Phenotypes for gene: ATP6V1A were set to Cutis laxa, autosomal recessive, type IID (MIM# 617403)
Penetrance for gene: ATP6V1A were set to unknown
Review for gene: ATP6V1A was set to GREEN
Added comment: PMID: 28065471;
- 3 families (including 2 consanguineous) with homozygous missense
- in vitro assays using patients' fibroblasts demonstrated the variants disrupted V-ATPase complex assembly and stability
Sources: Literature
Cataract v0.176 CTDP1 Zornitza Stark edited their review of gene: CTDP1: Changed rating: GREEN
Cataract v0.176 CTDP1 Zornitza Stark edited their review of gene: CTDP1: Changed publications: 14517542, 24690360, 25529582
Cataract v0.176 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Cataract v0.176 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Amber List (Moderate Evidence).
Cataract v0.176 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from to Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168
Cataract v0.175 CTDP1 Zornitza Stark Publications for gene: CTDP1 were set to
Cataract v0.174 CTDP1 Zornitza Stark Mode of inheritance for gene: CTDP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.173 CTDP1 Zornitza Stark Classified gene: CTDP1 as Amber List (moderate evidence)
Cataract v0.173 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Amber List (Moderate Evidence).
Cataract v0.172 CTDP1 Zornitza Stark Tag founder tag was added to gene: CTDP1.
Cataract v0.172 CTDP1 Zornitza Stark reviewed gene: CTDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14517542, 24690360; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, MIM# 604168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.172 DYRK1A Zornitza Stark Marked gene: DYRK1A as ready
Cataract v0.172 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Red List (Low Evidence).
Cataract v0.172 DYRK1A Seb Lunke gene: DYRK1A was added
gene: DYRK1A was added to Cataract. Sources: Literature
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1A were set to 28053047; 25944381
Phenotypes for gene: DYRK1A were set to congenital cataracts
Review for gene: DYRK1A was set to RED
Added comment: Really only one patient where cataract has been attributed directly to DYRK1A variant, 13 others with DYRK1A variants did not have cataracts (28053047). Second mention of cataract the gene was part of a large multi-gene deletion, and again other patients with DYRK1A (28053047) variants did not have cataract. Insufficient evidence.
Sources: Literature
Mendeliome v0.3265 DNMBP Seb Lunke Marked gene: DNMBP as ready
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3265 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Mendeliome v0.3265 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Mendeliome v0.3264 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Cataract v0.171 DNMBP Seb Lunke Marked gene: DNMBP as ready
Cataract v0.171 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Cataract v0.171 DNMBP Seb Lunke Classified gene: DNMBP as Green List (high evidence)
Cataract v0.171 DNMBP Seb Lunke Gene: dnmbp has been classified as Green List (High Evidence).
Cataract v0.170 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Cataract. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Differences of Sex Development v0.34 WDR11 Teresa Zhao reviewed gene: WDR11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20887964, PMID: 29263200; Phenotypes: Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3263 CRYGA Zornitza Stark Marked gene: CRYGA as ready
Mendeliome v0.3263 CRYGA Zornitza Stark Gene: cryga has been classified as Red List (Low Evidence).
Mendeliome v0.3263 CRYGA Zornitza Stark gene: CRYGA was added
gene: CRYGA was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: CRYGA.
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Phenotypes for gene: CRYGA were set to Cataract
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Expert list
Cataract v0.169 CRYGA Seb Lunke Tag refuted was removed from gene: CRYGA.
Tag disputed tag was added to gene: CRYGA.
Cataract v0.169 CRYGA Zornitza Stark Tag refuted tag was added to gene: CRYGA.
Mendeliome v0.3262 AKR1E2 Zornitza Stark Marked gene: AKR1E2 as ready
Mendeliome v0.3262 AKR1E2 Zornitza Stark Gene: akr1e2 has been classified as Red List (Low Evidence).
Mendeliome v0.3262 AKR1E2 Zornitza Stark gene: AKR1E2 was added
gene: AKR1E2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071
Phenotypes for gene: AKR1E2 were set to congenital cataracts
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Expert list
Cataract v0.169 ADAMTSL4 Zornitza Stark Marked gene: ADAMTSL4 as ready
Cataract v0.169 ADAMTSL4 Zornitza Stark Gene: adamtsl4 has been classified as Red List (Low Evidence).
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Marked gene: ADAMTSL4 as ready
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Gene: adamtsl4 has been classified as Green List (High Evidence).
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis, isolated, autosomal recessive, MIM# 225100
Mendeliome v0.3260 ADAMTSL4 Zornitza Stark Publications for gene: ADAMTSL4 were set to
Mendeliome v0.3259 ADAMTSL4 Zornitza Stark Mode of inheritance for gene: ADAMTSL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark Tag founder tag was added to gene: ADAMTSL4.
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19200529, 20564469, 20141359, 21051722; Phenotypes: Ectopia lentis, isolated, autosomal recessive, MIM# 225100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.169 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cataract v0.169 ABHD12 Zornitza Stark Phenotypes for gene: ABHD12 were changed from Polyneuropathy; Hearing loss; Ataxia; Retinitis pigmentosa; Cataracts to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674
Cataract v0.168 ABHD12 Zornitza Stark reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, MIM# 612674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Mendeliome v0.3258 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Mendeliome v0.3258 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from to Growth delay, microcephaly and intellectual disability
Mendeliome v0.3257 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Mendeliome v0.3256 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3255 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.168 CRYGA Seb Lunke Marked gene: CRYGA as ready
Cataract v0.168 CRYGA Seb Lunke Gene: cryga has been classified as Red List (Low Evidence).
Cataract v0.168 CRYGA Seb Lunke gene: CRYGA was added
gene: CRYGA was added to Cataract. Sources: Literature
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Literature
Microcephaly v0.139 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Microcephaly v0.139 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Microcephaly v0.139 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from to Growth delay, microcephaly and intellectual disability
Microcephaly v0.138 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Microcephaly v0.137 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.136 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.167 AKR1E2 Seb Lunke Marked gene: AKR1E2 as ready
Cataract v0.167 AKR1E2 Seb Lunke Gene: akr1e2 has been classified as Red List (Low Evidence).
Cataract v0.167 AKR1E2 Seb Lunke gene: AKR1E2 was added
gene: AKR1E2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071; 26622071
Phenotypes for gene: AKR1E2 were set to congenital cararact
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Literature
Cataract v0.166 ADAMTSL4 Seb Lunke gene: ADAMTSL4 was added
gene: ADAMTSL4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ADAMTSL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTSL4 were set to 22338190; 20702823
Phenotypes for gene: ADAMTSL4 were set to ectopia lentis; cataract
Review for gene: ADAMTSL4 was set to RED
Added comment: Early onset cataract described in multiple patients with variants in ADAMTSL4 as a secondary manifestation to Ectopia lentis et pupillae (MIM 225200)
Sources: Literature
Cataract v0.165 ABHD12 Seb Lunke Marked gene: ABHD12 as ready
Cataract v0.165 ABHD12 Seb Lunke Gene: abhd12 has been classified as Green List (High Evidence).
Cataract v0.165 ABHD12 Seb Lunke Classified gene: ABHD12 as Green List (high evidence)
Cataract v0.165 ABHD12 Seb Lunke Gene: abhd12 has been classified as Green List (High Evidence).
Cataract v0.164 ABHD12 Seb Lunke gene: ABHD12 was added
gene: ABHD12 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD12 were set to 32077159; 29571850; 28448692; 24697911
Phenotypes for gene: ABHD12 were set to Polyneuropathy; Hearing loss; Ataxia; Retinitis pigmentosa; Cataracts
Added comment: Two siblings each from two families with hom nonsense and PHARC syndrome and early on-set cataract, and a complex homozygous nonsense variant in an adult with early on-set cataract have been descibed recently in addition to original mutations described in 11 families from 4 different countries (Fiskerstrand et al (2010)). Total over 10 independent cases mentioned in literature.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Classified gene: HIST1H4C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Gene: hist1h4c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2736 HIST1H4C Seb Lunke reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cataract v0.162 PLOD3 Zornitza Stark edited their review of gene: PLOD3: Changed rating: GREEN
Cataract v0.162 PLOD3 Zornitza Stark edited their review of gene: PLOD3: Changed phenotypes: Lysyl hydroxylase 3 deficiency, MIM#612394
Cataract v0.162 POLG Zornitza Stark Marked gene: POLG as ready
Cataract v0.162 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Cataract v0.162 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to POLG-related disorders
Cataract v0.161 POLG Zornitza Stark Publications for gene: POLG were set to
Cataract v0.160 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.159 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791, 29358615, 22405928; Phenotypes: POLG-related disorders; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.159 RIC1 Zornitza Stark Marked gene: RIC1 as ready
Cataract v0.159 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Cataract v0.159 RIC1 Zornitza Stark Classified gene: RIC1 as Amber List (moderate evidence)
Cataract v0.159 RIC1 Zornitza Stark Gene: ric1 has been classified as Amber List (Moderate Evidence).
Cataract v0.158 RIC1 Zornitza Stark gene: RIC1 was added
gene: RIC1 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIC1 were set to 27878435; 31932796
Phenotypes for gene: RIC1 were set to CATIFA syndrome, MIM# 618761
Review for gene: RIC1 was set to AMBER
Added comment: 8 individuals from two consanguineous families, homozygous for same missense variant (founder effect). Cataract is a key feature of the phenotype.
Sources: Expert list
Cataract v0.157 SLC16A12 Zornitza Stark Marked gene: SLC16A12 as ready
Cataract v0.157 SLC16A12 Zornitza Stark Gene: slc16a12 has been classified as Green List (High Evidence).
Cataract v0.157 SLC16A12 Zornitza Stark Phenotypes for gene: SLC16A12 were changed from to Cataract 47, juvenile, with microcornea 612018
Cataract v0.156 SLC16A12 Zornitza Stark Publications for gene: SLC16A12 were set to
Cataract v0.155 SLC16A12 Zornitza Stark Mode of inheritance for gene: SLC16A12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.154 SLC16A12 Zornitza Stark reviewed gene: SLC16A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 20181839, 21778275, 18304496, 29088427; Phenotypes: Cataract 47, juvenile, with microcornea 612018; Mode of inheritance: None
Cataract v0.154 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Cataract v0.154 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Cataract v0.154 WFS1 Zornitza Stark Classified gene: WFS1 as Green List (high evidence)
Cataract v0.154 WFS1 Zornitza Stark Gene: wfs1 has been classified as Green List (High Evidence).
Cataract v0.153 WFS1 Zornitza Stark gene: WFS1 was added
gene: WFS1 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFS1 were set to 32350710
Phenotypes for gene: WFS1 were set to Wolfram syndrome 1, MIM# 222300
Review for gene: WFS1 was set to GREEN
Added comment: Cataracts reported in ~40% in a cohort of affected individuals.
Sources: Expert list
Cataract v0.152 XYLT2 Zornitza Stark Marked gene: XYLT2 as ready
Cataract v0.152 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Cataract v0.152 XYLT2 Zornitza Stark Classified gene: XYLT2 as Green List (high evidence)
Cataract v0.152 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Cataract v0.151 XYLT2 Zornitza Stark gene: XYLT2 was added
gene: XYLT2 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT2 were set to 26027496
Phenotypes for gene: XYLT2 were set to Spondyloocular syndrome, MIM# 605822
Review for gene: XYLT2 was set to GREEN
Added comment: Cataracts are a key feature of this condition.
Sources: Expert list
Deafness_IsolatedAndComplex v0.360 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.360 PNPT1 Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.359 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 23084290; 31752325
Deafness_IsolatedAndComplex v0.358 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Changed rating: GREEN
Deafness_IsolatedAndComplex v0.358 PNPT1 Lilian Downie reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30244537; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.71 TOR1A Zornitza Stark Marked gene: TOR1A as ready
Arthrogryposis v0.71 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Arthrogryposis v0.71 TOR1A Zornitza Stark Classified gene: TOR1A as Green List (high evidence)
Arthrogryposis v0.71 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Marked gene: RASGRP2 as ready
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Arthrogryposis v0.70 TOR1A Michelle Torres changed review comment from: 5 patients reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature; to: 5 families reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Classified gene: RASGRP2 as Green List (high evidence)
Bleeding and Platelet Disorders v0.23 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v0.22 RASGRP2 Zornitza Stark gene: RASGRP2 was added
gene: RASGRP2 was added to Bleeding Disorders. Sources: Literature
Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP2 were set to 24958846; 32609603; 32041177; 31724816; 30849270
Phenotypes for gene: RASGRP2 were set to Bleeding disorder, platelet-type, 18, MIM# 615888
Review for gene: RASGRP2 was set to GREEN
Added comment: Multiple affected families reported.
Sources: Literature
Ciliary Dyskinesia v0.121 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from Joubert syndrome 10, MIM 300804; Orofaciodigital syndrome I, MIM 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM 300209 to Joubert syndrome 10, MIM 300804; Orofaciodigital syndrome I, MIM 311200; Simpson-Golabi-Behmel syndrome, type 2, MIM 300209; Primary ciliary dyskinesia
Ciliary Dyskinesia v0.120 OFD1 Zornitza Stark Classified gene: OFD1 as Green List (high evidence)
Ciliary Dyskinesia v0.120 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark changed review comment from: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 3 individuals reported with PCD phenotype.; to: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 7 individuals reported with PCD phenotype.
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: GREEN
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed publications: 31366608, 31373179
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.119 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed publications: 31373179
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark changed review comment from: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel.; to: The conditions associated with this gene are not primary ciliary dyskinesias. Gene is appropriate for Ciliopathy panel. However, note 3 individuals reported with PCD phenotype.
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200, Primary ciliary dyskinesia
Ciliary Dyskinesia v0.118 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: AMBER
Mendeliome v0.3255 SFTPA1 Zornitza Stark Marked gene: SFTPA1 as ready
Mendeliome v0.3255 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3255 SFTPA1 Zornitza Stark Phenotypes for gene: SFTPA1 were changed from to Idiopathic pulmonary fibrosis
Mendeliome v0.3254 SFTPA1 Zornitza Stark Publications for gene: SFTPA1 were set to
Mendeliome v0.3253 SFTPA1 Zornitza Stark Mode of inheritance for gene: SFTPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3252 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Mendeliome v0.3252 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 SFTPA1 Zornitza Stark reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679, 30854216, 28869238, 26792177; Phenotypes: Idiopathic pulmonary fibrosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Marked gene: SFTPA1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Amber List (moderate evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.6 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.5 SFTPA1 Zornitza Stark gene: SFTPA1 was added
gene: SFTPA1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: SFTPA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SFTPA1 were set to 31601679; 30854216; 28869238; 26792177
Phenotypes for gene: SFTPA1 were set to Idiopathic pulmonary fibrosis
Review for gene: SFTPA1 was set to AMBER
Added comment: Four families and a mouse model, bi-allelic disease appears to be more severe, earlier onset.
Sources: Literature
Mendeliome v0.3251 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.118 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.117 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Hereditary Spastic Paraplegia v0.113 Zornitza Stark removed gene:STUB1 from the panel
Hereditary Neuropathy v0.73 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Hereditary Neuropathy v0.73 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.72 STUB1 Zornitza Stark gene: STUB1 was added
gene: STUB1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STUB1 were set to 32342324; 32337344
Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768
Review for gene: STUB1 was set to GREEN
Added comment: PMID: 32342324 - Gene causes both AD and AR spinocerebellar ataxia. Reviews 17 families (31 patients, adolescent/childhood onset), all patients developed progressive cerebellar ataxia, associated with dysmetria and dysarthria, corticospinal signs (19/31), myoclonus (7/31) and generalized tonic– clonic seizures (4/31), peripheral nervous system involvement (4/12). PMID: 32337344 - 1 large family with adult-onset gait disturbance and cognitive decline. Neuropathy is a feature of the more severe, bi-allelic disorder.
Sources: Literature
Hereditary Spastic Paraplegia v0.112 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.112 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Arthrogryposis v0.70 TOR1A Michelle Torres gene: TOR1A was added
gene: TOR1A was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: TOR1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1A were set to PMID: 30244176
Phenotypes for gene: TOR1A were set to Arthrogryposis
Review for gene: TOR1A was set to GREEN
Added comment: 5 patients reported by multiple authors supporting that biallelic mutations (missense, inframe del and protein truncating) in TOR1A cause severe arthrogryposis. Other variable features are developmental delay, strabismus and tremor. Parents carriers do not have symptoms of autosomal dominant dystonia, also associate with this gene and known to have incomplete penetrance (OMIM).
Sources: Literature
Ichthyosis and Porokeratosis v0.82 SREBF1 Zornitza Stark Marked gene: SREBF1 as ready
Ichthyosis and Porokeratosis v0.82 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Ichthyosis and Porokeratosis v0.82 SREBF1 Zornitza Stark Classified gene: SREBF1 as Green List (high evidence)
Ichthyosis and Porokeratosis v0.82 SREBF1 Zornitza Stark Gene: srebf1 has been classified as Green List (High Evidence).
Ichthyosis and Porokeratosis v0.81 SREBF1 Zornitza Stark gene: SREBF1 was added
gene: SREBF1 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.8 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3249 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3249 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Mendeliome v0.3249 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3248 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Marked gene: MT-CO3 as ready
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Gene: mt-co3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Classified gene: MT-CO3 as Green List (high evidence)
Mitochondrial disease v0.449 MT-CO3 Zornitza Stark Gene: mt-co3 has been classified as Green List (High Evidence).
Mendeliome v0.3248 LGR4 Zornitza Stark Marked gene: LGR4 as ready
Mendeliome v0.3248 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3248 LGR4 Zornitza Stark Publications for gene: LGR4 were set to
Mendeliome v0.3247 LGR4 Zornitza Stark Phenotypes for gene: LGR4 were changed from to Delayed puberty
Ichthyosis and Porokeratosis v0.80 ASPRV1 Zornitza Stark Marked gene: ASPRV1 as ready
Ichthyosis and Porokeratosis v0.80 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Ichthyosis and Porokeratosis v0.80 ASPRV1 Zornitza Stark Classified gene: ASPRV1 as Green List (high evidence)
Ichthyosis and Porokeratosis v0.80 ASPRV1 Zornitza Stark Gene: asprv1 has been classified as Green List (High Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Marked gene: SREBF1 as ready
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Mendeliome v0.3246 SREBF1 Seb Lunke Classified gene: SREBF1 as Green List (high evidence)
Mendeliome v0.3246 SREBF1 Seb Lunke Gene: srebf1 has been classified as Green List (High Evidence).
Regression v0.126 TBCE Zornitza Stark Marked gene: TBCE as ready
Regression v0.126 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2736 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Regression v0.126 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Regression v0.126 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.111 TBCE Zornitza Stark Marked gene: TBCE as ready
Hereditary Spastic Paraplegia v0.111 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.111 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Hereditary Spastic Paraplegia v0.111 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Marked gene: BTG4 as ready
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Mendeliome v0.3245 BTG4 Seb Lunke Classified gene: BTG4 as Green List (high evidence)
Mendeliome v0.3245 BTG4 Seb Lunke Gene: btg4 has been classified as Green List (High Evidence).
Mendeliome v0.3244 TRIP13 Seb Lunke Marked gene: TRIP13 as ready
Mendeliome v0.3244 TRIP13 Seb Lunke Gene: trip13 has been classified as Green List (High Evidence).
Mendeliome v0.3244 LGR4 Zornitza Stark Mode of inheritance for gene: LGR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3243 LGR4 Zornitza Stark Classified gene: LGR4 as Amber List (moderate evidence)
Mendeliome v0.3243 LGR4 Zornitza Stark Gene: lgr4 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson changed review comment from: At least 6 male cases in 5 unrelated families reported with hydrocephalus with Hirchsprung disease.
Sources: Expert list; to: At least 6 male cases in 5 unrelated families reported with hydrocephalus and Hirchsprung disease/intestinal pseudo-obstruction.
Sources: Expert list
Leukodystrophy v0.168 LAMB1 Zornitza Stark Marked gene: LAMB1 as ready
Leukodystrophy v0.168 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.168 LAMB1 Zornitza Stark Classified gene: LAMB1 as Amber List (moderate evidence)
Leukodystrophy v0.168 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.167 LAMB1 Zornitza Stark gene: LAMB1 was added
gene: LAMB1 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: LAMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB1 were set to 29888467; 25925986
Phenotypes for gene: LAMB1 were set to Cystic leukoencephalopathy
Review for gene: LAMB1 was set to AMBER
Added comment: Two unrelated families reported with cystic leukoencephalopathy and bi-allelic variants in this gene. Also note adult-onset leukodystrophy reported in one individual.
Sources: Literature
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Marked gene: L1CAM as ready
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Gene: l1cam has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Classified gene: L1CAM as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.27 L1CAM Bryony Thompson Gene: l1cam has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.26 L1CAM Bryony Thompson gene: L1CAM was added
gene: L1CAM was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: L1CAM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: L1CAM were set to 9279760; 11857550; 15148591; 15368500; 22354677
Phenotypes for gene: L1CAM were set to Hydrocephalus with Hirschsprung disease or congenital idiopathic intestinal pseudoobstruction MIM#307000
Review for gene: L1CAM was set to GREEN
Added comment: At least 6 male cases in 5 unrelated families reported with hydrocephalus with Hirchsprung disease.
Sources: Expert list
Regression v0.125 TBCE Elena Savva gene: TBCE was added
gene: TBCE was added to Regression. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PMID: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy 617207
Review for gene: TBCE was set to GREEN
Added comment: PMID: 27666369 - 6 patients (4 families) with early-onset, progressive neurodegeneration encephalopathy with spinal muscular atrophy, supported by functional studies. Patients present within the first 18 months of life, phenotypes include hypotonia (3/6), dev delay (6/6), signs of regression (6/6, distal amyotrophy, ataxia, spasticity)
Missense variant p.I155N is recurring, very rare in gnomAD.
Sources: Literature
Ichthyosis and Porokeratosis v0.79 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3242 SREBF1 Paul De Fazio gene: SREBF1 was added
gene: SREBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
gene: SREBF1 was marked as current diagnostic
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Hereditary Spastic Paraplegia v0.110 TBCE Elena Savva gene: TBCE was added
gene: TBCE was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PMID: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy 617207
Review for gene: TBCE was set to GREEN
Added comment: PMID: 27666369 - 6 patients (4 families) with early-onset, progressive neurodegeneration encephalopathy with spinal muscular atrophy, supported by functional studies.
Patients present within the first 18 months of life, phenotypes include hypotonia (3/6), dev delay (6/6), signs of regression (6/6, distal amyotrophy, ataxia, spasticity)

Missense variant p.I155N is recurring, very rare in gnomAD.
Sources: Expert list
Mendeliome v0.3242 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Mendeliome v0.3242 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 BTG4 Ain Roesley edited their review of gene: BTG4: Changed rating: GREEN
Mendeliome v0.3241 BTG4 Ain Roesley gene: BTG4 was added
gene: BTG4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BTG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTG4 were set to PMID: 32502391
Phenotypes for gene: BTG4 were set to Zygotic cleavage failure (ZCF)
Penetrance for gene: BTG4 were set to unknown
Added comment: PMID: 32502391
- 4 affecteds from 4 families including 3 consanguineous families. 3 PTVs + 1 splice.
- in vitro assays in HELA cells showed all PTVs had complete loss of protein. The missense variant had abolished interaction with CNOT7
- In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF
Sources: Literature
Hereditary Spastic Paraplegia v0.110 STUB1 Elena Savva gene: STUB1 was added
gene: STUB1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: STUB1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: STUB1 were set to PMID: 32342324; 32337344
Phenotypes for gene: STUB1 were set to ?Spinocerebellar ataxia 48 618093; Spinocerebellar ataxia, autosomal recessive 16 615768
Review for gene: STUB1 was set to GREEN
Added comment: PMID: 32342324 - Gene causes both AD and AR spinocerebellar ataxia. Reviews 17 families (31 patients, adolescent/childhood onset), all patients developed progressive cerebellar ataxia, associated with dysmetria and dysarthria, corticospinal signs (19/31), myoclonus (7/31) and generalized tonic–
clonic seizures (4/31), peripheral nervous system involvement (4/12).

PMID: 32337344 - 1 large family with adult-onset gait disturbance and cognitive decline
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2736 SLC12A2 Seb Lunke Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Classified gene: SLC12A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Added comment: Comment on list classification: Two independent families and mouse model
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Gene: slc12a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 SLC12A2 Seb Lunke reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3241 KIAA1217 Zornitza Stark Marked gene: KIAA1217 as ready
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3241 KIAA1217 Zornitza Stark Classified gene: KIAA1217 as Amber List (moderate evidence)
Mendeliome v0.3241 KIAA1217 Zornitza Stark Gene: kiaa1217 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3240 KIAA1217 Zornitza Stark gene: KIAA1217 was added
gene: KIAA1217 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIAA1217 were set to 32369272
Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic
Review for gene: KIAA1217 was set to AMBER
Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense.
Sources: Literature
Mendeliome v0.3239 TRIP13 Ain Roesley reviewed gene: TRIP13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32473092; Phenotypes: female infertility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 TRIP13 Ain Roesley Deleted their review
Mendeliome v0.3239 LGR4 Elena Savva reviewed gene: LGR4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32493844; Phenotypes: {Bone mineral density, low, susceptibility to} 615311; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 TRIP13 Ain Roesley gene: TRIP13 was added
gene: TRIP13 was added to Amenorrhoea. Sources: Literature
Mode of inheritance for gene: TRIP13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP13 were set to PMID: 32473092
Phenotypes for gene: TRIP13 were set to female infertility
Penetrance for gene: TRIP13 were set to unknown
Review for gene: TRIP13 was set to GREEN
Added comment: PMID: 32473092;
- 5 patients from 4 families (including 1 consanguineous) diagnosed with primary infertility with normal menstrual cycles.
- all missense variants
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 IL17RD Lauren Akesson reviewed gene: IL17RD: Rating: RED; Mode of pathogenicity: None; Publications: 32389901, 23643382; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia (MIM# 615267); Mode of inheritance: Unknown
Mendeliome v0.3239 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2733 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 HS6ST1 Lauren Akesson reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.3238 HOXD10 Zornitza Stark reviewed gene: HOXD10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3238 HOXD10 Zornitza Stark Marked gene: HOXD10 as ready
Mendeliome v0.3238 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Mendeliome v0.3238 HOXD10 Zornitza Stark Phenotypes for gene: HOXD10 were changed from to Charcot-Marie-Tooth disease, foot deformity of; Vertical talus, congenital (MIM#192950)
Mendeliome v0.3237 HOXD10 Zornitza Stark Publications for gene: HOXD10 were set to
Hereditary Neuropathy v0.71 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
Hereditary Neuropathy v0.71 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.71 SGPL1 Zornitza Stark Classified gene: SGPL1 as Amber List (moderate evidence)
Hereditary Neuropathy v0.71 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3236 HOXD10 Zornitza Stark Mode of inheritance for gene: HOXD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3235 HOXD10 Zornitza Stark Classified gene: HOXD10 as Red List (low evidence)
Mendeliome v0.3235 HOXD10 Zornitza Stark Gene: hoxd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v0.18 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Cerebral Palsy v0.18 ADD3 Zornitza Stark Gene: add3 has been classified as Green List (High Evidence).
Cerebral Palsy v0.18 ADD3 Zornitza Stark Classified gene: ADD3 as Green List (high evidence)
Cerebral Palsy v0.18 ADD3 Zornitza Stark Gene: add3 has been classified as Green List (High Evidence).
Cataract v0.150 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Cataract v0.150 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Cataract v0.150 ADD3 Zornitza Stark Classified gene: ADD3 as Amber List (moderate evidence)
Cataract v0.150 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3234 HOXD10 Crystle Lee reviewed gene: HOXD10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15146389, 16450407; Phenotypes: Charcot-Marie-Tooth disease, foot deformity of, Vertical talus, congenital (MIM#192950); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral Palsy v0.17 ADD3 Zornitza Stark gene: ADD3 was added
gene: ADD3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to GREEN
Added comment: Four families reported.
Sources: Expert Review
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Added comment: Comment when marking as ready: Microcephaly is borderline.
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Classified gene: ADD3 as Amber List (moderate evidence)
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Classified gene: ATP6AP2 as Green List (high evidence)
Early-onset Parkinson disease v0.33 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.70 Zornitza Stark removed gene:ATP6AP2 from the panel
Early-onset Parkinson disease v0.32 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Early-onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to 30985297; 23595882
Phenotypes for gene: ATP6AP2 were set to Parkinsonism with spasticity, X-linked, MIM# 300911
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 30985297 - 1 de novo male patient with postnatal neurodegeneration, seizures, mild face dysmorphism. Sequential MRI revealed decreasing gray and white matter volumes. Patient has a splice variant proven to cause alternative transcript expression. Supported by null mouse model.

PMID: 23595882 - 2 patients (1 family) with a synonymous variant proven to affect splicing. Patients have X-linked parkinsonian syndrome

Summary: 2 unrelated patients + animal models
Sources: Expert list
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Macrocephaly_Megalencephaly v0.42 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Arthrogryposis v0.70 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Arthrogryposis v0.70 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Arthrogryposis v0.70 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Arthrogryposis v0.70 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Regression v0.125 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Regression v0.125 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Regression v0.125 CACNA1E Zornitza Stark Classified gene: CACNA1E as Green List (high evidence)
Regression v0.125 CACNA1E Zornitza Stark Gene: cacna1e has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.110 GLRX5 Zornitza Stark reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spasticity, childhood-onset, with hyperglycinemia, MIM# 616859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.110 GLRX5 Zornitza Stark Marked gene: GLRX5 as ready
Hereditary Spastic Paraplegia v0.110 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.110 GLRX5 Zornitza Stark Classified gene: GLRX5 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.110 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.109 GLRX5 Zornitza Stark Classified gene: GLRX5 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.109 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.166 GLRX5 Zornitza Stark Marked gene: GLRX5 as ready
Leukodystrophy v0.166 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Leukodystrophy v0.166 GLRX5 Zornitza Stark Classified gene: GLRX5 as Green List (high evidence)
Leukodystrophy v0.166 GLRX5 Zornitza Stark Gene: glrx5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.741 ADPRHL2 Zornitza Stark Phenotypes for gene: ADPRHL2 were changed from to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170)
Genetic Epilepsy v0.740 ADPRHL2 Zornitza Stark Publications for gene: ADPRHL2 were set to
Genetic Epilepsy v0.739 ADPRHL2 Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.738 GRN Zornitza Stark Marked gene: GRN as ready
Genetic Epilepsy v0.738 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.738 GRN Zornitza Stark Classified gene: GRN as Green List (high evidence)
Genetic Epilepsy v0.738 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.3234 ADPRHL2 Zornitza Stark Phenotypes for gene: ADPRHL2 were changed from to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170
Mendeliome v0.3233 ADPRHL2 Zornitza Stark Publications for gene: ADPRHL2 were set to
Hereditary Neuropathy v0.69 SGPL1 Crystle Lee gene: SGPL1 was added
gene: SGPL1 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 28077491; 28165339; 30274713; 28165343
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 (MIM#617575)
Review for gene: SGPL1 was set to AMBER
Added comment: Peripheral neuropathy has been reported in patients however does not appear to be consistent feature.

PMID: 28077491: Reported as a cause of CMT in 2 sibs

PMID: 28165339: Reported 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects. Peripheral neuropathy (motor and sensory) reported in one family.

PMID: 30274713: Review article.
Sources: Expert Review
Mendeliome v0.3232 ADPRHL2 Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3231 ADPRHL2 Zornitza Stark edited their review of gene: ADPRHL2: Changed publications: 30100084, 30401461
Regression v0.124 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Regression v0.124 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Mendeliome v0.3231 ADPRHL2 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Regression v0.124 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Regression v0.124 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Regression v0.123 ADPRHL2 Zornitza Stark gene: ADPRHL2 was added
gene: ADPRHL2 was added to Regression. Sources: Expert list
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30100084; 30401461
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM# 618170
Review for gene: ADPRHL2 was set to GREEN
Added comment: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Hereditary Neuropathy v0.69 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Hereditary Neuropathy v0.69 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.69 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Hereditary Neuropathy v0.69 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.108 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Hereditary Spastic Paraplegia v0.108 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.108 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.108 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Regression v0.122 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Regression v0.122 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Regression v0.122 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Regression v0.122 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia and Chorea v0.70 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Dystonia and Chorea v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia and Chorea v0.70 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Dystonia and Chorea v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.107 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Hereditary Spastic Paraplegia v0.107 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.107 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.107 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.68 FDX2 Zornitza Stark Marked gene: FDX2 as ready
Hereditary Neuropathy v0.68 FDX2 Zornitza Stark Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.68 FDX2 Zornitza Stark Classified gene: FDX2 as Amber List (moderate evidence)
Hereditary Neuropathy v0.68 FDX2 Zornitza Stark Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.106 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Hereditary Spastic Paraplegia v0.106 RAB3GAP2 Zornitza Stark Added comment: Comment when marking as ready: Syndromic spasticity.
Hereditary Spastic Paraplegia v0.106 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.106 RAB3GAP2 Zornitza Stark Classified gene: RAB3GAP2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.106 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.105 RAB3GAP2 Elena Savva gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: RAB3GAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP2 were set to PMID: 32376645
Phenotypes for gene: RAB3GAP2 were set to Martsolf syndrome 212720
Review for gene: RAB3GAP2 was set to GREEN
Added comment: PMID: 32376645 - 1 patient with bilateral clinodactyly and syndactyly, normal MRI and learning difficulties. Review of previous reports notes 9 additional patients (4 families) with Marsolf syndrome, with postnatal microcephaly (5/9), congenital cataracts (7/9), limb spasticity (7/9) and optic nerve atrophy (2/9).
Sources: Literature
Mendeliome v0.3231 GPR161 Zornitza Stark Marked gene: GPR161 as ready
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3231 GPR161 Zornitza Stark Classified gene: GPR161 as Green List (high evidence)
Mendeliome v0.3231 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Mendeliome v0.3230 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Hereditary Neuropathy v0.67 FDX2 Crystle Lee gene: FDX2 was added
gene: FDX2 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 30010796; 24281368; 28803783
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy (MIM#251900)
Review for gene: FDX2 was set to AMBER
Added comment: Gene previously known as FDX1L. Limited evidence (1 family) suporting neuropathy being a feature of the associated condition

PMID: 30010796: Reported same variant in 2 apparently unrelated Brazilian families. Axonal
sensori-motor polyneuropathy reported in 4 out of the 6 patients. OMIM notes that peripheral neuropathy has onset in the second decade.
Sources: Expert Review
Hereditary Spastic Paraplegia v0.105 MAPK8IP3 Elena Savva gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8IP3 were set to PMID: 30612693; 30945334
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities 618443
Review for gene: MAPK8IP3 was set to GREEN
Added comment: PMID: 30612693 - 13 unrelated children patients with de novo variants, supported by functional studies. Patients have developmental delay (13/13), spasticity (4/13), ataxia (2/13), unstable gait (1/13), microcephaly (3/13), generalized seizures (3/13). No signs of regression, but cerebellar atrophy (3/12), thin corpus callosum (4/10), perisylvian polymicrogyria (2/12), white matter loss (4/12) was noted

PMID: 30945334 - 5 child patients (4 families) with spastic diplegia (4/5), ID (5/5), epilepsy (2/5) and cerebellar atrophy (5/5), corpus callosum hypoplasia (5/5). No regression.
Sources: Expert list
Dystonia and Chorea v0.69 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to GREEN
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Literature
Regression v0.121 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Regression. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to GREEN
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Literature
Hereditary Spastic Paraplegia v0.105 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to AMBER
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Expert list
Hereditary Neuropathy v0.67 ADPRHL2 Crystle Lee gene: ADPRHL2 was added
gene: ADPRHL2 was added to Hereditary Neuropathy - complex. Sources: Expert Review
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30100084; 30401461
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170)
Review for gene: ADPRHL2 was set to GREEN
Added comment: Peripheral (sensori-)motor axonal neuropathy is a feature of this progressive neurodegenerative disorder. >5 families have been reported.
Sources: Expert Review
Genetic Epilepsy v0.737 GRN Elena Savva gene: GRN was added
gene: GRN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRN were set to PMID: 22608501; 31855245
Phenotypes for gene: GRN were set to Ceroid lipofuscinosis, neuronal, 11 614706
Review for gene: GRN was set to GREEN
Added comment: PMID: 22608501 - 2 siblings with a homozygous PTC and neuronal ceroid lipofuscinosis. Both showed vision deterioration in their mid 20s, with MRI revealing cerebellar atrophy and ataxia

PMID: 31855245 - 6 patients (4 families) with homozygous PTCs and start-loss. 5/6 report vision impairement, 6/6 cognitive deterioration, 3/6 cerebellar involvement, 3/6 seizures. Reviews previous reports, age of onset varies from 7-56 years old and seizures reported in a total of 7/11 patients.
Sources: Literature
Genetic Epilepsy v0.737 ADPRHL2 Crystle Lee reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30100084, 30401461; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Marked gene: GPR161 as ready
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Classified gene: GPR161 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.14 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Leukodystrophy v0.165 GLRX5 Elena Savva gene: GLRX5 was added
gene: GLRX5 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLRX5 were set to PMID: 24334290; 30770271
Phenotypes for gene: GLRX5 were set to Spasticity, childhood-onset, with hyperglycinemia 616859
Review for gene: GLRX5 was set to GREEN
Added comment: PMID: 24334290 - 3 patients (3 families) with non-ketotic hyperglycinemia, supported by functional studies. Patients had normal development with childhood-onset spastic paraplegia (3/3), spinal lesion (1/3), optic atrophy (1/3) and brain signal abnormalities involving the frontal and parietal white matter (2/3)

PMID: 30770271 - 1 patient with childhood onset cavitating leukoencephalopathy.

p.Lys51del is a recurring mutation.
Sources: Literature
Hereditary Spastic Paraplegia v0.105 GLRX5 Elena Savva gene: GLRX5 was added
gene: GLRX5 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLRX5 were set to PMID: 24334290; 30770271
Phenotypes for gene: GLRX5 were set to Spasticity, childhood-onset, with hyperglycinemia 616859
Review for gene: GLRX5 was set to AMBER
Added comment: PMID: 24334290 - 3 patients (3 families) with non-ketotic hyperglycinemia, supported by functional studies. Patients had normal development with childhood-onset spastic paraplegia (3/3), spinal lesion (1/3), optic atrophy (1/3) and brain signal abnormalities involving the frontal and parietal white matter (2/3)

PMID: 30770271 - 1 patient with childhood onset cavitating leukoencephalopathy.

p.Lys51del is a recurring mutation.
Sources: Expert list
Regression v0.121 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Regression. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Review for gene: CACNA1E was set to GREEN
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Arthrogryposis v0.69 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Macrocephaly_Megalencephaly v0.41 CACNA1E Elena Savva gene: CACNA1E was added
gene: CACNA1E was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to PMID: 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69 618285
Mode of pathogenicity for gene: CACNA1E was set to Other
Review for gene: CACNA1E was set to GREEN
Added comment: PMID: 30343943 - 30 patients with de novo variants and early-onset developmental and epileptic encephalopathy. Patients had developmental regression (9/30), severe hypotonia (16/30), seizures (26/30), congenital joint contractures (13/30), macrocephaly (13/30). MRI shows white matter loss, cortical atrophy
Variants showed a GOF and LOF.
Sources: Literature
Hereditary Neuropathy v0.67 ATP6AP2 Elena Savva gene: ATP6AP2 was added
gene: ATP6AP2 was added to Hereditary Neuropathy - complex. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to PMID: 30985297; 23595882
Phenotypes for gene: ATP6AP2 were set to ?Parkinsonism with spasticity, X-linked 300911
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 30985297 - 1 de novo male patient with postnatal neurodegeneration, seizures, mild face dysmorphism. Sequential MRI revealed decreasing gray and white matter volumes. Patient has a splice variant proven to cause alternative transcript expression. Supported by null mouse model.

PMID: 23595882 - 2 patients (1 family) with a synonymous variant proven to affect splicing. Patients have X-linked parkinsonian syndrome

Summary: 2 unrelated patients + animal models
Sources: Expert list
Cancer Predisposition_Paediatric v0.13 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Microcephaly v0.135 ADD3 Elena Savva gene: ADD3 was added
gene: ADD3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to PMID: 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to GREEN
Added comment: PMID: 29768408;23836506 - 9/10 patients (4 families) with borderline microcephaly
Sources: Literature
Cataract v0.149 ADD3 Elena Savva gene: ADD3 was added
gene: ADD3 was added to Cataract. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to PMID: 29768408; 23836506
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to AMBER
Added comment: PMID: 29768408;23836506 - 4/5 patients (2 families) with early-onset bilateral cataracts

Two families, emerging gene
Sources: Literature
Mendeliome v0.3229 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Mendeliome v0.3229 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Mendeliome v0.3229 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from to Epilepsy with myoclonic absences; intellectual disability; SETD1B-related neurodevelopmental disorder
Mendeliome v0.3228 SETD1B Zornitza Stark Publications for gene: SETD1B were set to
Mendeliome v0.3227 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3226 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566, 29322246, 31440728, 31685013; Phenotypes: Epilepsy with myoclonic absences, intellectual disability, SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.737 SETD1B Zornitza Stark changed review comment from: At least 3, possibly 5, individuals reported with de novo variants in this gene and a neurodevelopmental disorder including seizures.; to: At least 7, possibly 9, individuals reported with de novo variants in this gene and a neurodevelopmental disorder including seizures.
Genetic Epilepsy v0.737 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed phenotypes: Epilepsy with myoclonic absences, intellectual disability, SETD1B-related neurodevelopmental disorder
Genetic Epilepsy v0.737 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed publications: 32546566, 29322246, 31440728, 31685013
Genetic Epilepsy v0.737 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from Epilepsy with myoclonic absences; intellectual disability to Epilepsy with myoclonic absences; intellectual disability; SETD1B-related neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.2732 SETD1B Zornitza Stark Publications for gene: SETD1B were set to 32546566
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark changed review comment from: At least 4 unrelated individuals reported.; to: At least 7 unrelated individuals reported.
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed publications: 32546566, 29322246, 31440728, 31685013
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from to SETD1B-related neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.2730 SETD1B Zornitza Stark Publications for gene: SETD1B were set to
Intellectual disability syndromic and non-syndromic v0.2729 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2728 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566; Phenotypes: SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3226 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3226 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Mendeliome v0.3226 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Mendeliome v0.3225 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Periventricular Grey Matter Heterotopia v0.9 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.8 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Periventricular Grey Matter Heterotopia. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2728 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Intellectual disability syndromic and non-syndromic v0.2727 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Polymicrogyria and Schizencephaly v0.89 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Polymicrogyria and Schizencephaly v0.88 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Marked gene: MAP1B as ready
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Gene: map1b has been classified as Green List (High Evidence).
Periventricular Grey Matter Heterotopia v0.7 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Mendeliome v0.3224 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Mendeliome v0.3223 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Periventricular Grey Matter Heterotopia v0.6 MAP1B Zornitza Stark Publications for gene: MAP1B were set to
Periventricular Grey Matter Heterotopia v0.5 MAP1B Zornitza Stark Mode of inheritance for gene: MAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Periventricular Grey Matter Heterotopia v0.4 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Overgrowth v0.57 SUZ12 Zornitza Stark Marked gene: SUZ12 as ready
Overgrowth v0.57 SUZ12 Zornitza Stark Gene: suz12 has been classified as Green List (High Evidence).
Overgrowth v0.57 SUZ12 Zornitza Stark Phenotypes for gene: SUZ12 were changed from to Imagawa-Matsumoto syndrome, MIM# 618786
Overgrowth v0.56 SUZ12 Zornitza Stark Publications for gene: SUZ12 were set to
Overgrowth v0.55 SUZ12 Zornitza Stark Mode of inheritance for gene: SUZ12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.54 SUZ12 Zornitza Stark reviewed gene: SUZ12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31736240, 28229514; Phenotypes: Imagawa-Matsumoto syndrome, MIM# 618786; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.54 RNF125 Zornitza Stark changed review comment from: At least 3 unrelated families reported.; to: At least 3 unrelated families reported, overgrowth is a key feature.
Overgrowth v0.54 RNF125 Zornitza Stark Marked gene: RNF125 as ready
Overgrowth v0.54 RNF125 Zornitza Stark Gene: rnf125 has been classified as Green List (High Evidence).
Overgrowth v0.54 RNF125 Zornitza Stark Phenotypes for gene: RNF125 were changed from to Tenorio syndrome, MIM# 616260
Overgrowth v0.53 RNF125 Zornitza Stark Publications for gene: RNF125 were set to
Overgrowth v0.52 RNF125 Zornitza Stark Mode of inheritance for gene: RNF125 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.51 RNF125 Zornitza Stark reviewed gene: RNF125: Rating: GREEN; Mode of pathogenicity: None; Publications: 25196541; Phenotypes: Tenorio syndrome, MIM# 616260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.51 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Overgrowth v0.51 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Red List (Low Evidence).
Overgrowth v0.51 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from to Basal cell nevus syndrome, MIM# 109400
Overgrowth v0.50 PTCH1 Zornitza Stark Classified gene: PTCH1 as Red List (low evidence)
Overgrowth v0.50 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Red List (Low Evidence).
Overgrowth v0.49 PTCH1 Zornitza Stark reviewed gene: PTCH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal cell nevus syndrome, MIM# 109400; Mode of inheritance: None
Overgrowth v0.49 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Overgrowth v0.49 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Red List (Low Evidence).
Overgrowth v0.49 PPP2R5D Zornitza Stark Phenotypes for gene: PPP2R5D were changed from to Mental retardation, autosomal dominant 35, MIM# 616355
Overgrowth v0.48 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Overgrowth v0.47 PPP2R5D Zornitza Stark Mode of inheritance for gene: PPP2R5D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.46 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Red List (low evidence)
Overgrowth v0.46 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Red List (Low Evidence).
Overgrowth v0.45 PPP2R5D Zornitza Stark reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: 26168268, 25972378, 25533962; Phenotypes: Mental retardation, autosomal dominant 35, MIM# 616355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.45 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Overgrowth v0.45 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Overgrowth v0.45 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Cowden syndrome 5, MIM# 615108
Overgrowth v0.44 PIK3CA Zornitza Stark Publications for gene: PIK3CA were set to
Overgrowth v0.43 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.42 PIK3CA Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23246288, 32362992, 31929958; Phenotypes: Cowden syndrome 5, MIM# 615108; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.42 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Overgrowth v0.42 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Overgrowth v0.42 PHF6 Zornitza Stark Phenotypes for gene: PHF6 were changed from to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
Overgrowth v0.41 PHF6 Zornitza Stark Mode of inheritance for gene: PHF6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.40 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
Overgrowth v0.40 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Overgrowth v0.39 PHF6 Zornitza Stark reviewed gene: PHF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, MIM# 301900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.39 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Overgrowth v0.39 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Overgrowth v0.39 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Kosaki overgrowth syndrome, MIM# 616592
Overgrowth v0.38 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Overgrowth v0.37 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.36 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25454926, 32291752, 30941910, 29226947; Phenotypes: Kosaki overgrowth syndrome, MIM# 616592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.36 Zornitza Stark removed gene:NPR3 from the panel
Overgrowth v0.35 NPR3 Zornitza Stark changed review comment from: Four affected individuals from three unrelated families.; to: Four affected individuals from three unrelated families, however phenotype is more Marfanoid, rather than generalised overgrowth.
Overgrowth v0.35 NPR3 Zornitza Stark edited their review of gene: NPR3: Changed rating: AMBER
Overgrowth v0.35 MED12 Zornitza Stark Marked gene: MED12 as ready
Overgrowth v0.35 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.35 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Lujan-Fryns syndrome, MIM# 309520; Opitz-Kaveggia syndrome, MIM# 305450
Overgrowth v0.34 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.33 MED12 Zornitza Stark Classified gene: MED12 as Amber List (moderate evidence)
Overgrowth v0.33 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.32 MED12 Zornitza Stark reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lujan-Fryns syndrome, MIM# 309520, Opitz-Kaveggia syndrome, MIM# 305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Overgrowth v0.32 KMT5B Zornitza Stark Classified gene: KMT5B as Amber List (moderate evidence)
Overgrowth v0.32 KMT5B Zornitza Stark Gene: kmt5b has been classified as Amber List (Moderate Evidence).
Overgrowth v0.31 KMT5B Zornitza Stark changed review comment from: Tendency towards taller height reported in some affected individuals.; to: Tendency towards taller height reported in some affected individuals, overgrowth is not a prominent/consistent feature.
Overgrowth v0.31 KMT5B Zornitza Stark edited their review of gene: KMT5B: Changed rating: AMBER
Overgrowth v0.31 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Overgrowth v0.31 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.31 GLI3 Zornitza Stark Classified gene: GLI3 as Amber List (moderate evidence)
Overgrowth v0.31 GLI3 Zornitza Stark Gene: gli3 has been classified as Amber List (Moderate Evidence).
Overgrowth v0.30 GLI3 Zornitza Stark reviewed gene: GLI3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Overgrowth v0.30 DIS3L2 Zornitza Stark Tag SV/CNV tag was added to gene: DIS3L2.
Overgrowth v0.30 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Overgrowth v0.30 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Overgrowth v0.30 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from to Perlman syndrome, MIM# 267000
Overgrowth v0.29 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Overgrowth v0.28 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Overgrowth v0.27 DIS3L2 Zornitza Stark reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22306653, 28328139, 29950491; Phenotypes: Perlman syndrome, MIM# 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Overgrowth v0.27 AKT2 Zornitza Stark Marked gene: AKT2 as ready
Overgrowth v0.27 AKT2 Zornitza Stark Gene: akt2 has been classified as Green List (High Evidence).
Overgrowth v0.27 AKT2 Zornitza Stark Classified gene: AKT2 as Green List (high evidence)
Overgrowth v0.27 AKT2 Zornitza Stark Gene: akt2 has been classified as Green List (High Evidence).
Overgrowth v0.26 AKT2 Zornitza Stark gene: AKT2 was added
gene: AKT2 was added to Overgrowth. Sources: Expert list
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT2 were set to 21979934
Phenotypes for gene: AKT2 were set to Hypoinsulinemic hypoglycemia with hemihypertrophy, MIM# 240900
Mode of pathogenicity for gene: AKT2 was set to Other
Review for gene: AKT2 was set to GREEN
Added comment: Three unrelated individuals reported with same de novo recurring missense variant, postulated to be activating, E17K.
Sources: Expert list
Overgrowth v0.25 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Overgrowth v0.25 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Overgrowth v0.25 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome
Overgrowth v0.24 ABCC9 Zornitza Stark Publications for gene: ABCC9 were set to
Overgrowth v0.23 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.22 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.31 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines); Metachondromatosis, 156250 AD; Noonan syndrome 1, 163950 AD; Leukemia, juvenile myelomonocytic, somatic, 607785 to LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines); Noonan syndrome 1, 163950 AD
Mendeliome v0.3223 MRAS Zornitza Stark Marked gene: MRAS as ready
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3223 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Mendeliome v0.3223 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Rasopathy v0.30 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Rasopathy v0.30 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.3222 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
Mendeliome v0.3222 MRAS Zornitza Stark edited their review of gene: MRAS: Changed rating: GREEN; Changed publications: 28289718, 31173466, 31108500, 31173466
Rasopathy v0.29 MRAS Zornitza Stark changed review comment from: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list; to: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert list
Rasopathy v0.29 MRAS Zornitza Stark edited their review of gene: MRAS: Changed publications: 28289718, 31173466, 31108500, 31173466
Rasopathy v0.29 MRAS Zornitza Stark edited their review of gene: MRAS: Changed rating: GREEN; Changed publications: 28289718, 31173466, 31108500
Mendeliome v0.3222 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Rasopathy v0.28 MRAS Zornitza Stark Marked gene: MRAS as ready
Rasopathy v0.28 MRAS Zornitza Stark Gene: mras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.28 MRAS Zornitza Stark Classified gene: MRAS as Amber List (moderate evidence)
Rasopathy v0.28 MRAS Zornitza Stark Gene: mras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.27 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Rasopathy. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Rasopathy v0.26 RRAS Zornitza Stark Marked gene: RRAS as ready
Rasopathy v0.26 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.26 RRAS Zornitza Stark Phenotypes for gene: RRAS were changed from to Noonan syndrome
Rasopathy v0.25 RRAS Zornitza Stark Publications for gene: RRAS were set to
Rasopathy v0.24 RRAS Zornitza Stark Mode of inheritance for gene: RRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.23 RRAS Zornitza Stark Classified gene: RRAS as Amber List (moderate evidence)
Rasopathy v0.23 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Rasopathy v0.22 RRAS Zornitza Stark reviewed gene: RRAS: Rating: AMBER; Mode of pathogenicity: None; Publications: 24705357; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.22 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.3221 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Mendeliome v0.3221 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3221 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Mendeliome v0.3220 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Mendeliome v0.3219 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3218 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Mendeliome v0.3218 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Mendeliome v0.3217 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.41 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Macrocephaly_Megalencephaly v0.40 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Macrocephaly_Megalencephaly v0.39 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.38 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.38 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Macrocephaly_Megalencephaly v0.37 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.36 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.21 A2ML1 Zornitza Stark Marked gene: A2ML1 as ready
Rasopathy v0.21 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Rasopathy v0.21 A2ML1 Zornitza Stark Phenotypes for gene: A2ML1 were changed from to Noonan syndrome
Rasopathy v0.20 A2ML1 Zornitza Stark Publications for gene: A2ML1 were set to
Rasopathy v0.19 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed publications: 24939586, 25862627
Rasopathy v0.19 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed publications: 24939586
Rasopathy v0.19 A2ML1 Zornitza Stark Classified gene: A2ML1 as Red List (low evidence)
Rasopathy v0.19 A2ML1 Zornitza Stark Gene: a2ml1 has been classified as Red List (Low Evidence).
Rasopathy v0.18 A2ML1 Zornitza Stark Tag disputed tag was added to gene: A2ML1.
Rasopathy v0.18 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed rating: RED
Rasopathy v0.18 A2ML1 Zornitza Stark changed review comment from: Three unrelated individuals reported with de novo missense variants in this gene, zebrafish model.; to: Four unrelated individuals reported with de novo missense variants in this gene, zebrafish model. However, p.Arg802His is present in 168 heterozygotes in gnomad and one homozygote; p.Arg802Leu is also present in 168 heterozygotes, 1 homozygote; and p.Arg592Leu is present in 105 heterozygotes. Rated as DISPUTED by ClinGen.
Rasopathy v0.18 A2ML1 Zornitza Stark edited their review of gene: A2ML1: Changed rating: AMBER; Changed publications: 25862627
Rasopathy v0.18 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.17 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24939586; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.130 ACTB Zornitza Stark Marked gene: ACTB as ready
Craniosynostosis v0.130 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Craniosynostosis v0.130 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from to Baraitser-Winter syndrome 1, MIM# 243310
Craniosynostosis v0.129 ACTB Zornitza Stark Mode of inheritance for gene: ACTB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.128 ACTG1 Zornitza Stark Marked gene: ACTG1 as ready
Craniosynostosis v0.128 ACTG1 Zornitza Stark Gene: actg1 has been classified as Green List (High Evidence).
Craniosynostosis v0.128 ACTG1 Zornitza Stark Phenotypes for gene: ACTG1 were changed from to Baraitser-Winter syndrome 2, MIM# 614583
Craniosynostosis v0.127 ACTG1 Zornitza Stark Mode of inheritance for gene: ACTG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.126 MASP1 Zornitza Stark Marked gene: MASP1 as ready
Craniosynostosis v0.126 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Craniosynostosis v0.126 SKI Zornitza Stark Marked gene: SKI as ready
Craniosynostosis v0.126 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Craniosynostosis v0.126 TLK2 Zornitza Stark Marked gene: TLK2 as ready
Craniosynostosis v0.126 TLK2 Zornitza Stark Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.126 TLK2 Zornitza Stark Phenotypes for gene: TLK2 were changed from to Mental retardation, autosomal dominant 57, MIM#618050
Craniosynostosis v0.125 TLK2 Zornitza Stark Publications for gene: TLK2 were set to
Craniosynostosis v0.124 TLK2 Zornitza Stark Mode of inheritance for gene: TLK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.123 TLK2 Zornitza Stark Classified gene: TLK2 as Amber List (moderate evidence)
Craniosynostosis v0.123 TLK2 Zornitza Stark Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.25 TMEM70 Bryony Thompson edited their review of gene: TMEM70: Changed rating: AMBER
Gastrointestinal neuromuscular disease v0.25 TMEM70 Bryony Thompson gene: TMEM70 was added
gene: TMEM70 was added to Gastrointestinal neuromuscular disease. Sources: NHS GMS
Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM70 were set to 21147908
Phenotypes for gene: TMEM70 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 MIM#614052
Review for gene: TMEM70 was set to RED
Added comment: Intestinal pseudo-obstruction reported in one case and delayed gastric emptying reported in another case. Gastrointestinal neuromuscular disease does not appear to be a prominent feature of the condition.
Sources: NHS GMS
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Marked gene: ATRX as ready
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Gene: atrx has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Classified gene: ATRX as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.24 ATRX Bryony Thompson Gene: atrx has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.23 ATRX Bryony Thompson gene: ATRX was added
gene: ATRX was added to Gastrointestinal neuromuscular disease. Sources: NHS GMS
Mode of inheritance for gene: ATRX 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: ATRX were set to 16688741
Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome MIM#301040
Review for gene: ATRX was set to GREEN
Added comment: Gastrointestinal problems can be a prominent feature of the condition.
Sources: NHS GMS
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson Marked gene: LMOD1 as ready
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.22 LMOD1 Bryony Thompson reviewed gene: LMOD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28292896; Phenotypes: Megacystis microcolon intestinal hypoperistalsis syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson Marked gene: MYL9 as ready
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson Gene: myl9 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.22 MYL9 Bryony Thompson gene: MYL9 was added
gene: MYL9 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL9 were set to 29453416
Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome
Review for gene: MYL9 was set to RED
Added comment: Single consanguineous family reported with a homozygous deletion including the last exon of the gene. No functional evidence.
Sources: Literature
Craniosynostosis v0.121 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Craniosynostosis v0.121 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.121 TMCO1 Zornitza Stark Classified gene: TMCO1 as Amber List (moderate evidence)
Craniosynostosis v0.121 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.120 TMCO1 Zornitza Stark gene: TMCO1 was added
gene: TMCO1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMCO1 were set to 20018682; 24424126; 24194475
Phenotypes for gene: TMCO1 were set to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Review for gene: TMCO1 was set to AMBER
Added comment: Craniosynostosis reported in a small number of affected individuals, also note founder mutation in Amish.
Sources: Expert list
Craniosynostosis v0.119 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Craniosynostosis v0.119 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Craniosynostosis v0.119 TFAP2B Zornitza Stark Classified gene: TFAP2B as Green List (high evidence)
Craniosynostosis v0.119 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Craniosynostosis v0.118 TFAP2B Zornitza Stark gene: TFAP2B was added
gene: TFAP2B was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: TFAP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TFAP2B were set to 31292255
Phenotypes for gene: TFAP2B were set to Syndromic craniosynostosis
Review for gene: TFAP2B was set to GREEN
Added comment: Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Sources: Expert list
Gastrointestinal neuromuscular disease v0.21 RET Bryony Thompson Classified gene: RET as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.21 RET Bryony Thompson Gene: ret has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson Marked gene: SEMA3D as ready
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson Gene: sema3d has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.20 SEMA3D Bryony Thompson gene: SEMA3D was added
gene: SEMA3D was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SEMA3D was set to Unknown
Publications for gene: SEMA3D were set to 28334784; 25839327
Phenotypes for gene: SEMA3D were set to Hirschsprung disease
Review for gene: SEMA3D was set to RED
Added comment: Reported as a common susceptibility loci. No reported evidence for an association with Mendelian disease. Sema3d null heterozygote and homozygote mouse model had normal intestinal innervation.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson edited their review of gene: SEMA3C: Changed publications: 25839327, 31240788
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson Marked gene: SEMA3C as ready
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson Gene: sema3c has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.19 SEMA3C Bryony Thompson gene: SEMA3C was added
gene: SEMA3C was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SEMA3C was set to Unknown
Publications for gene: SEMA3C were set to 25839327
Phenotypes for gene: SEMA3C were set to Hirschsprung disease
Review for gene: SEMA3C was set to RED
Added comment: Common susceptibility loci for Hirschsprung disease. No reported evidence that it is associated with Mendelian disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson Marked gene: NRG3 as ready
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson Gene: nrg3 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.18 NRG3 Bryony Thompson gene: NRG3 was added
gene: NRG3 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRG3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG3 were set to 23315268
Phenotypes for gene: NRG3 were set to Hirschsprung disease
Review for gene: NRG3 was set to RED
Added comment: Single Chinese mother and son reported, and some sporadic cases that appear to have recurrent variants that may be polymorphisms. No functional evidence.
Sources: Expert list
Mendeliome v0.3217 NRG1 Bryony Thompson Marked gene: NRG1 as ready
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3217 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Mendeliome v0.3217 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3216 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson changed review comment from: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list; to: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Marked gene: NRG1 as ready
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Classified gene: NRG1 as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.17 NRG1 Bryony Thompson Gene: nrg1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.16 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Craniosynostosis v0.117 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Craniosynostosis v0.117 STAT3 Zornitza Stark Gene: stat3 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.117 STAT3 Zornitza Stark Classified gene: STAT3 as Amber List (moderate evidence)
Craniosynostosis v0.117 STAT3 Zornitza Stark Gene: stat3 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.116 STAT3 Zornitza Stark gene: STAT3 was added
gene: STAT3 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 20159255
Phenotypes for gene: STAT3 were set to Hyper-IgE recurrent infection syndrome, MIM# 147060
Review for gene: STAT3 was set to AMBER
Added comment: Craniosynostosis is a rarely described feature of this condition.
Sources: Expert list
Craniosynostosis v0.115 SPECC1L Zornitza Stark Phenotypes for gene: SPECC1L were changed from Hypertelorism, Teebi type MIM#145420 to Hypertelorism, Teebi type MIM#145420; Opitz GBBB syndrome, type II, MIM#145410
Craniosynostosis v0.114 SPECC1L Zornitza Stark Publications for gene: SPECC1L were set to 26111080; 30472488
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson Marked gene: ECE1 as ready
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson Gene: ece1 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.15 ECE1 Bryony Thompson gene: ECE1 was added
gene: ECE1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: ECE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ECE1 were set to 9915973
Phenotypes for gene: ECE1 were set to ?Hirschsprung disease, cardiac defects, and autonomic dysfunction MIM#613870
Review for gene: ECE1 was set to RED
Added comment: A single case reported with Arg742Cys. Although this variant causes a loss of function in in vitro assays the NFE AF is higher than expected for a dominant disorder (0.0004, 50/127,302 alleles).
Sources: Expert list
Deafness_IsolatedAndComplex v0.358 FOXI1 Lilian Downie commented on gene: FOXI1: Disputed evidence for enlarged vestibular aqueduct PMID: 19204907
Craniosynostosis v0.113 SPECC1L Zornitza Stark Classified gene: SPECC1L as Green List (high evidence)
Craniosynostosis v0.113 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Craniosynostosis v0.112 SPECC1L Zornitza Stark reviewed gene: SPECC1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 25412741; Phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410; Mode of inheritance: None
Craniosynostosis v0.112 SMAD3 Zornitza Stark Phenotypes for gene: SMAD3 were changed from LOEYS-DIETZ SYNDROME to Loeys-Dietz syndrome 3, MIM# 613795
Craniosynostosis v0.111 SMAD3 Zornitza Stark Publications for gene: SMAD3 were set to 20301312
Craniosynostosis v0.110 SMAD3 Zornitza Stark reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29392890; Phenotypes: Loeys-Dietz syndrome 3, MIM# 613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.110 PHEX Zornitza Stark Marked gene: PHEX as ready
Craniosynostosis v0.110 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Craniosynostosis v0.110 PHEX Zornitza Stark Classified gene: PHEX as Green List (high evidence)
Craniosynostosis v0.110 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Craniosynostosis v0.109 PHEX Zornitza Stark gene: PHEX was added
gene: PHEX was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: PHEX was set to Other
Publications for gene: PHEX were set to 19242361; 17551721
Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant, MIM# 307800
Review for gene: PHEX was set to GREEN
Added comment: Craniosynostosis reported in around ~40% of affected individuals.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.14 GDNF Bryony Thompson changed review comment from: Mouse models have a gastrointestinal neuromuscular phenotype, however there is no evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list; to: Mouse models have a gastrointestinal neuromuscular phenotype, however there is limited evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson Marked gene: NRTN as ready
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson Gene: nrtn has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.14 NRTN Bryony Thompson gene: NRTN was added
gene: NRTN was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: NRTN was set to Unknown
Publications for gene: NRTN were set to 21206993; 10069332; 9700200
Phenotypes for gene: NRTN were set to Hirschsprung disease
Review for gene: NRTN was set to RED
Added comment: A mouse model has a gastrointestinal neuromuscular phenotype, however there is limited evidence that variants in NRTN cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson edited their review of gene: GDNF: Changed publications: 18276829, 8896568, 8657308, 11973622, 21206993
Craniosynostosis v0.108 P4HB Zornitza Stark Marked gene: P4HB as ready
Craniosynostosis v0.108 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Craniosynostosis v0.108 P4HB Zornitza Stark Classified gene: P4HB as Green List (high evidence)
Craniosynostosis v0.108 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Craniosynostosis v0.107 P4HB Zornitza Stark gene: P4HB was added
gene: P4HB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: P4HB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: P4HB were set to 25683117; 29384951
Phenotypes for gene: P4HB were set to Cole-Carpenter syndrome 1, MIM# 112240
Review for gene: P4HB was set to GREEN
Added comment: Craniosynostosis is a feature of this syndrome.
Sources: Expert list
Craniosynostosis v0.106 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Craniosynostosis v0.106 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.106 JAG1 Zornitza Stark Classified gene: JAG1 as Amber List (moderate evidence)
Craniosynostosis v0.106 JAG1 Zornitza Stark Gene: jag1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.105 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 29530693; 12244552
Phenotypes for gene: JAG1 were set to Alagille syndrome 1, MIM# 118450
Review for gene: JAG1 was set to AMBER
Added comment: Craniosynostosis is rarely described in Alagille syndrome, functional data to support role of JAG1 in suture development.
Sources: Expert list
Craniosynostosis v0.104 IHH Zornitza Stark Marked gene: IHH as ready
Craniosynostosis v0.104 IHH Zornitza Stark Gene: ihh has been classified as Green List (High Evidence).
Craniosynostosis v0.104 IHH Zornitza Stark Classified gene: IHH as Green List (high evidence)
Craniosynostosis v0.104 IHH Zornitza Stark Gene: ihh has been classified as Green List (High Evidence).
Craniosynostosis v0.103 IHH Zornitza Stark gene: IHH was added
gene: IHH was added to Craniosynostosis. Sources: Expert list
SV/CNV, 5'UTR tags were added to gene: IHH.
Mode of inheritance for gene: IHH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IHH were set to Craniosynostosis, Philadelphia type
Mode of pathogenicity for gene: IHH was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: IHH was set to GREEN
Added comment: Green for promoter region 40kb upstream of IHH only. Duplications of 2q35-q36.3 encompassing region 40kb upstream of IHH (within intron of NHEJ1 gene) cause craniosynostosis. Please note SNVs in this gene cause a different phenotype.
Sources: Expert list
Craniosynostosis v0.102 IDUA Zornitza Stark Marked gene: IDUA as ready
Craniosynostosis v0.102 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Craniosynostosis v0.102 IDUA Zornitza Stark Classified gene: IDUA as Green List (high evidence)
Craniosynostosis v0.102 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Craniosynostosis v0.101 IDUA Zornitza Stark gene: IDUA was added
gene: IDUA was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 23917744
Phenotypes for gene: IDUA were set to Mucopolysaccharidosis Ih/s (Hurler syndrome) 607014; 607016
Review for gene: IDUA was set to GREEN
Added comment: Craniosynostosis of at least one suture was present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants.
Sources: Expert list
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson Marked gene: GDNF as ready
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson Gene: gdnf has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.13 GDNF Bryony Thompson gene: GDNF was added
gene: GDNF was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: GDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDNF were set to 18276829; 8896568; 8657308; 11973622
Phenotypes for gene: GDNF were set to {Hirschsprung disease, susceptibility to, 3} MIM#613711
Review for gene: GDNF was set to RED
Added comment: Mouse models have a gastrointestinal neuromuscular phenotype, however there is no evidence that variants in GDNF cause Hirschsprung disease or a gastrointestinal neuromuscular disease in humans.
Sources: Expert list
Craniosynostosis v0.100 IDS Zornitza Stark Marked gene: IDS as ready
Craniosynostosis v0.100 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Craniosynostosis v0.100 IDS Zornitza Stark Classified gene: IDS as Green List (high evidence)
Craniosynostosis v0.100 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Craniosynostosis v0.99 IDS Zornitza Stark gene: IDS was added
gene: IDS was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IDS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDS were set to 15314824
Phenotypes for gene: IDS were set to Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900
Review for gene: IDS was set to GREEN
Added comment: Craniosynostosis of at least one suture reported as present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants.
Sources: Expert list
Craniosynostosis v0.98 GNPTAB Zornitza Stark Marked gene: GNPTAB as ready
Craniosynostosis v0.98 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Craniosynostosis v0.98 GNPTAB Zornitza Stark Classified gene: GNPTAB as Green List (high evidence)
Craniosynostosis v0.98 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Craniosynostosis v0.97 GNPTAB Zornitza Stark gene: GNPTAB was added
gene: GNPTAB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GNPTAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPTAB were set to 24891900; 24060719
Phenotypes for gene: GNPTAB were set to Mucolipidosis II alpha/beta(I cell disease), MIM# 252500
Review for gene: GNPTAB was set to GREEN
Added comment: Recognised complication of I-cell disease.
Sources: Expert list
Craniosynostosis v0.96 GNAS Zornitza Stark Marked gene: GNAS as ready
Craniosynostosis v0.96 GNAS Zornitza Stark Gene: gnas has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.96 GNAS Zornitza Stark Classified gene: GNAS as Amber List (moderate evidence)
Craniosynostosis v0.96 GNAS Zornitza Stark Gene: gnas has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.95 GNAS Zornitza Stark gene: GNAS was added
gene: GNAS was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAS were set to 19530187; 26340332; 26267576
Phenotypes for gene: GNAS were set to Pseudohypoparathyroidism type 1a, MIM# 103580; Craniosynostosis
Review for gene: GNAS was set to AMBER
Added comment: Craniosynostosis is a rare complication of pseudohyoparathyroidism, a small number of published cases.
Sources: Expert list
Craniosynostosis v0.94 FGF10 Zornitza Stark edited their review of gene: FGF10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.94 FGF10 Zornitza Stark Mode of inheritance for gene: FGF10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.93 FGF10 Zornitza Stark reviewed gene: FGF10: Rating: AMBER; Mode of pathogenicity: None; Publications: 29215649; Phenotypes: ; Mode of inheritance: None
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Marked gene: DSPP as ready
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Added comment: Comment when marking as ready: Three families altogether, two with the same variant, V18F. One with isolated deafness, two with dental phenotype as well as deafness. Some functional data to support impact on protein. Mouse model has dental phenotype.
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Gene: dspp has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v0.358 DSPP Zornitza Stark Publications for gene: DSPP were set to 29741433
Deafness_IsolatedAndComplex v0.357 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594 to Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594
Deafness_IsolatedAndComplex v0.356 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from to Deafness, autosomal dominant 39, with dentinogenesis, MIM# 605594
Deafness_IsolatedAndComplex v0.356 DSPP Zornitza Stark Publications for gene: DSPP were set to
Deafness_IsolatedAndComplex v0.355 DSPP Zornitza Stark Mode of inheritance for gene: DSPP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v0.354 DSPP Zornitza Stark Classified gene: DSPP as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v0.354 DSPP Zornitza Stark Gene: dspp has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Marked gene: MPV17 as ready
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Gene: mpv17 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Classified gene: MPV17 as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.12 MPV17 Bryony Thompson Gene: mpv17 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.11 MPV17 Bryony Thompson gene: MPV17 was added
gene: MPV17 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 22964873; 28673863; 22593919
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) MIM#256810
Review for gene: MPV17 was set to GREEN
Added comment: Gastrointestinal features including dysmotility have been reported in association biallelic variants in this gene in about 30% of cases with this condition, according to GeneReviews.
Sources: Expert list
Callosome v0.152 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Callosome v0.152 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Callosome v0.152 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Callosome v0.151 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Callosome v0.150 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.149 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Callosome v0.149 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Callosome v0.148 FLRT3 Zornitza Stark reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3215 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Mendeliome v0.3215 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3215 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Mendeliome v0.3214 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Mendeliome v0.3213 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3212 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Mendeliome v0.3212 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Mendeliome v0.3211 FLRT3 Zornitza Stark reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Added comment: Comment when marking as ready: Oligogenic inheritance postulated. I also note one of the variants, Gln69Lys is present in 7 individuals in gnomad.
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Differences of Sex Development v0.33 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 DSPP Lilian Downie reviewed gene: DSPP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29741433; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.19 HARS2 Lauren Akesson reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31827252, 31486067, 31449985, 27650058, 21464306; Phenotypes: Perrault syndrome 2 (MIM# 614926); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 GNRH1 Lauren Akesson reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32134721, 19567835, 19535795; Phenotypes: ?Hypogonadotropic hypogonadism 12 with or without anosmia (MIM# 614841); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.31 FLRT3 Lauren Akesson reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: Unknown
Ciliopathies v0.192 CCDC32 Zornitza Stark Marked gene: CCDC32 as ready
Ciliopathies v0.192 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Ciliopathies v0.192 CCDC32 Zornitza Stark Classified gene: CCDC32 as Green List (high evidence)
Ciliopathies v0.192 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Ciliopathies v0.191 CCDC32 Zornitza Stark gene: CCDC32 was added
gene: CCDC32 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to Craniofacial, cardiac, laterality and neurodevelopmental anomalies
Review for gene: CCDC32 was set to GREEN
Added comment: Two unrelated consanguineous families with probands with homozygous frameshift variants reported. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Mendeliome v0.3211 CCDC32 Zornitza Stark Marked gene: CCDC32 as ready
Mendeliome v0.3211 CCDC32 Zornitza Stark Added comment: Comment when marking as ready: Three affected individuals from two unrelated families, supportive animal model and other functional data consistent with this being a ciliopathy.
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Mendeliome v0.3211 CCDC32 Zornitza Stark Classified gene: CCDC32 as Green List (high evidence)
Mendeliome v0.3211 CCDC32 Zornitza Stark Gene: ccdc32 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Marked gene: CAPZA2 as ready
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2726 CAPZA2 Zornitza Stark gene: CAPZA2 was added
gene: CAPZA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to Intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3210 CAPZA2 Zornitza Stark Marked gene: CAPZA2 as ready
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3210 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Mendeliome v0.3210 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Marked gene: PPP3R1 as ready
Mendeliome v0.3209 PPP3R1 Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus; note multiple mouse models implicating a role for this gene in cardiovascular, renal and brain development.
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3209 PPP3R1 Zornitza Stark Classified gene: PPP3R1 as Red List (low evidence)
Mendeliome v0.3209 PPP3R1 Zornitza Stark Gene: ppp3r1 has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Marked gene: PLEK as ready
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Mendeliome v0.3208 PLEK Zornitza Stark Classified gene: PLEK as Red List (low evidence)
Mendeliome v0.3208 PLEK Zornitza Stark Gene: plek has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark Marked gene: CNRIP1 as ready
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v0.353 CNRIP1 Zornitza Stark gene: CNRIP1 was added
gene: CNRIP1 was added to Deafness. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3207 CNRIP1 Zornitza Stark Marked gene: CNRIP1 as ready
Mendeliome v0.3207 CNRIP1 Zornitza Stark Added comment: Comment when marking as ready: Currently just a locus, insufficient evidence for gene-disease association.
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3207 CNRIP1 Zornitza Stark Classified gene: CNRIP1 as Red List (low evidence)
Mendeliome v0.3207 CNRIP1 Zornitza Stark Gene: cnrip1 has been classified as Red List (Low Evidence).
Mendeliome v0.3206 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Mendeliome v0.3206 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Mendeliome v0.3206 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from to ?Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly
Mendeliome v0.3205 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757; 25575569; 32193685
Mendeliome v0.3204 RAD21 Zornitza Stark Publications for gene: RAD21 were set to
Mendeliome v0.3203 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3202 CAPZA2 Eleanor Williams gene: CAPZA2 was added
gene: CAPZA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3202 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PPP3R1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PLEK was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 RAD21 Sarah Leigh reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 31334757, 31704779; Phenotypes: Cornelia de Lange syndrome 4 614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Craniosynostosis v0.93 FREM1 Zornitza Stark Marked gene: FREM1 as ready
Craniosynostosis v0.93 FREM1 Zornitza Stark Gene: frem1 has been classified as Red List (Low Evidence).
Craniosynostosis v0.93 FREM1 Zornitza Stark Phenotypes for gene: FREM1 were changed from to Trigonocephaly 2, MIM# 614485
Craniosynostosis v0.92 FREM1 Zornitza Stark Publications for gene: FREM1 were set to
Craniosynostosis v0.91 FREM1 Zornitza Stark Mode of inheritance for gene: FREM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.90 FREM1 Zornitza Stark Classified gene: FREM1 as Red List (low evidence)
Craniosynostosis v0.90 FREM1 Zornitza Stark Gene: frem1 has been classified as Red List (Low Evidence).
Craniosynostosis v0.89 FREM1 Zornitza Stark Tag disputed tag was added to gene: FREM1.
Craniosynostosis v0.89 FREM1 Zornitza Stark reviewed gene: FREM1: Rating: RED; Mode of pathogenicity: None; Publications: 21931569,; Phenotypes: Trigonocephaly 2, MIM# 614485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.89 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Craniosynostosis v0.89 FAM20C Zornitza Stark Gene: fam20c has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.89 FAM20C Zornitza Stark Classified gene: FAM20C as Amber List (moderate evidence)
Craniosynostosis v0.89 FAM20C Zornitza Stark Gene: fam20c has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.88 FAM20C Zornitza Stark gene: FAM20C was added
gene: FAM20C was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to 19250384
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM# 259775
Review for gene: FAM20C was set to AMBER
Added comment: Osteosclerotic bone dysplasia with increased skull ossification. 2 unrelated cases with missense variants survived beyond infancy and had turribrachycephaly, one also had plagiocephaly.
Sources: Expert list
Craniosynostosis v0.87 CTSK Zornitza Stark Marked gene: CTSK as ready
Craniosynostosis v0.87 CTSK Zornitza Stark Gene: ctsk has been classified as Green List (High Evidence).
Craniosynostosis v0.87 CTSK Zornitza Stark Classified gene: CTSK as Green List (high evidence)
Craniosynostosis v0.87 CTSK Zornitza Stark Gene: ctsk has been classified as Green List (High Evidence).
Craniosynostosis v0.86 CTSK Zornitza Stark gene: CTSK was added
gene: CTSK was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: CTSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSK were set to 21968522; 23175007
Phenotypes for gene: CTSK were set to Pycnodysostosis, MIM#265800
Review for gene: CTSK was set to GREEN
Added comment: Craniosynostosis described in some individuals.
Sources: Expert list
Mendeliome v0.3202 CCDC32 Eleanor Williams gene: CCDC32 was added
gene: CCDC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies
Review for gene: CCDC32 was set to AMBER
Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Craniosynostosis v0.85 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Craniosynostosis v0.85 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Craniosynostosis v0.85 ASXL1 Zornitza Stark Classified gene: ASXL1 as Green List (high evidence)
Craniosynostosis v0.85 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Craniosynostosis v0.84 ASXL1 Zornitza Stark gene: ASXL1 was added
gene: ASXL1 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ASXL1 were set to Bohring-Opitz syndrome,MIM# 605039
Review for gene: ASXL1 was set to GREEN
Added comment: Trigonocephaly in 90%, metopic synostosis frequent.
Sources: Expert list
Craniosynostosis v0.83 ARSB Zornitza Stark Marked gene: ARSB as ready
Craniosynostosis v0.83 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Craniosynostosis v0.83 ARSB Zornitza Stark Classified gene: ARSB as Green List (high evidence)
Craniosynostosis v0.83 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Craniosynostosis v0.82 ARSB Zornitza Stark gene: ARSB was added
gene: ARSB was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSB were set to Mucopolysaccharidosis VI (MPS6, MIM# 253200
Review for gene: ARSB was set to GREEN
Added comment: Synostosis of at least one suture was present in 77% of 47 MPS cases (types I,II,VI, VII). >3 cases with IDUA, IDS, ARSB variants.
Sources: Expert list
Craniosynostosis v0.81 ACTG1 Zornitza Stark reviewed gene: ACTG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 2, MIM# 614583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.81 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Baraitser-Winter syndrome 1, MIM# 243310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Marked gene: ACVRL1 as ready
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Gene: acvrl1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Classified gene: ACVRL1 as Green List (high evidence)
Vascular Malformations_Somatic v0.15 ACVRL1 Zornitza Stark Gene: acvrl1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Classified gene: AKT3 as Green List (high evidence)
Vascular Malformations_Somatic v0.14 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Marked gene: RRM2B as ready
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Gene: rrm2b has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson edited their review of gene: RRM2B: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.10 RRM2B Bryony Thompson Mode of inheritance for gene: RRM2B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.9 RRM2B Bryony Thompson Classified gene: RRM2B as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.9 RRM2B Bryony Thompson Gene: rrm2b has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.8 RRM2B Bryony Thompson gene: RRM2B was added
gene: RRM2B was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: RRM2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to 19667227; 23107649
Phenotypes for gene: RRM2B were set to Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 MIM#613077
Review for gene: RRM2B was set to GREEN
Added comment: Gastrointestinal disturbances have been reported in 6/31 cases with adult onset cases with biallelic and monoallelic variants.
Sources: Expert list
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Marked gene: ENG as ready
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Gene: eng has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Classified gene: ENG as Green List (high evidence)
Vascular Malformations_Somatic v0.13 ENG Zornitza Stark Gene: eng has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Marked gene: GLMN as ready
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Classified gene: GLMN as Green List (high evidence)
Vascular Malformations_Somatic v0.12 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Marked gene: RASA1 as ready
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Classified gene: RASA1 as Green List (high evidence)
Vascular Malformations_Somatic v0.11 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Marked gene: TEK as ready
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Classified gene: TEK as Green List (high evidence)
Vascular Malformations_Somatic v0.10 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Marked gene: STAMBP as ready
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.110 STAMBP Zornitza Stark Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome to Microcephaly-capillary malformation syndrome, MIM# 614261
Vascular Malformations_Germline v0.109 STAMBP Zornitza Stark Publications for gene: STAMBP were set to
Vascular Malformations_Germline v0.108 STAMBP Zornitza Stark reviewed gene: STAMBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542699; Phenotypes: Microcephaly-capillary malformation syndrome, MIM# 614261; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Marked gene: SOX18 as ready
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Classified gene: SOX18 as Green List (high evidence)
Vascular Malformations_Germline v0.108 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.107 SOX18 Zornitza Stark gene: SOX18 was added
gene: SOX18 was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: SOX18 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOX18 were set to 12740761; 24697860; 2484451; 26148450
Phenotypes for gene: SOX18 were set to Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940
Review for gene: SOX18 was set to GREEN
Added comment: Both mono allelic and bi-allelic variants reported.
Sources: Expert list
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Marked gene: PDCD10 as ready
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Classified gene: PDCD10 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.106 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.105 PDCD10 Zornitza Stark reviewed gene: PDCD10: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations 3, MIM# 603285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Marked gene: GDF2 as ready
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.4 GDF2 Zornitza Stark Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506
Cerebral vascular malformations v0.3 GDF2 Zornitza Stark Publications for gene: GDF2 were set to
Cerebral vascular malformations v0.2 GDF2 Zornitza Stark Classified gene: GDF2 as Red List (low evidence)
Cerebral vascular malformations v0.2 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.1 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: RED; Mode of pathogenicity: None; Publications: 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.105 GDF2 Zornitza Stark Classified gene: GDF2 as Red List (low evidence)
Vascular Malformations_Germline v0.105 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark edited their review of gene: GDF2: Changed rating: RED
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Marked gene: GDF2 as ready
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Gene: gdf2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.104 GDF2 Zornitza Stark Publications for gene: GDF2 were set to
Vascular Malformations_Germline v0.103 GDF2 Zornitza Stark Classified gene: GDF2 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.103 GDF2 Zornitza Stark Gene: gdf2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.102 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM# 615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Marked gene: CCM2 as ready
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Gene: ccm2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.102 CCM2 Zornitza Stark Phenotypes for gene: CCM2 were changed from Cerebral cavernous malformations to Cerebral cavernous malformations-2, MIM# 603284
Vascular Malformations_Germline v0.101 CCM2 Zornitza Stark Publications for gene: CCM2 were set to
Vascular Malformations_Germline v0.100 CCM2 Zornitza Stark Classified gene: CCM2 as Amber List (moderate evidence)
Vascular Malformations_Germline v0.100 CCM2 Zornitza Stark Gene: ccm2 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.99 CCM2 Zornitza Stark Tag SV/CNV tag was added to gene: CCM2.
Vascular Malformations_Germline v0.99 CCM2 Zornitza Stark reviewed gene: CCM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21543988, 14624391; Phenotypes: Cerebral cavernous malformations-2, MIM# 603284; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Germline v0.99 ATR Zornitza Stark Marked gene: ATR as ready
Vascular Malformations_Germline v0.99 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson Marked gene: OPA1 as ready
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson Gene: opa1 has been classified as Red List (Low Evidence).
Gastrointestinal neuromuscular disease v0.7 OPA1 Bryony Thompson gene: OPA1 was added
gene: OPA1 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA1 were set to 30395865
Phenotypes for gene: OPA1 were set to gastrointestinal pseudo-obstruction
Review for gene: OPA1 was set to RED
Added comment: Cannot find evidence that gastrointestinal pseudo-obstruction or dysmotility have been reported in association with this gene. There is a single report of an OPA1 heterozygous variant in a case with suggestive MNGIE, but there were no obvious gastrointestinal features identified.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FGF8 Lauren Akesson reviewed gene: FGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20463092,18596921; Phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia (612702); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.6 Bryony Thompson Panel name changed from Visceral Myopathy to Gastrointestinal neuromuscular disease
Vascular Malformations_Germline v0.99 ATR Zornitza Stark gene: ATR was added
gene: ATR was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: ATR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATR were set to 22341969
Phenotypes for gene: ATR were set to Cutaneous telangiectasia and cancer syndrome, familial, MIM# 614564
Review for gene: ATR was set to RED
Added comment: Single multigenerational family reported.
Sources: Expert list
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Marked gene: ATM as ready
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Classified gene: ATM as Green List (high evidence)
Vascular Malformations_Germline v0.98 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.97 ATM Zornitza Stark gene: ATM was added
gene: ATM was added to Vascular Malformations_Germline. Sources: Expert list
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATM were set to Ataxia-telangiectasia, MIM# 208900
Review for gene: ATM was set to GREEN
Added comment: Cutaneous telangiectasia are a feature of this disorder.
Sources: Expert list
Vascular Malformations_Somatic v0.9 TEK Chris Richmond gene: TEK was added
gene: TEK was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEK were set to 27519652
Phenotypes for gene: TEK were set to Venous malformations, multiple cutaneous and mucosal (600195); Blue rubber bleb naevus syndrome; Sporadic multifocal vascular malformations
Penetrance for gene: TEK were set to unknown
Mode of pathogenicity for gene: TEK was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TEK was set to GREEN
Added comment: Gain of function. Germline:

Somatic: Blue Rubber Bleb Naevus Syndrome
PMID 27519652: "Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations" group studied tissue from 17 individuals with blue rubber bleb nevus and six individuals with sporadic multifocal vascular malformations. They found that most (13 of 15) individuals with blue rubber bleb nevus had tissue double mutations (i.e., two somatic TEK mutations); 10 of these double mutations were in cis, and in the other tissues the allelism could not be determined. Double and cis mutations were present in most sporadic multifocal vascular malformations as well.
Sources: Expert Review
Vascular Malformations_Somatic v0.9 RASA1 Chris Richmond gene: RASA1 was added
gene: RASA1 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RASA1 were set to 31300548; 30635911
Phenotypes for gene: RASA1 were set to Capillary malformation-arteriovenous malformation 1 (608354)
Penetrance for gene: RASA1 were set to Incomplete
Review for gene: RASA1 was set to GREEN
Added comment: PMID: 31300548: "Four distinct mosaic RASA1 mutations, with an allele frequency ranging from 3% to 25%, were identified in four index patients with classical capillary malformation-arteriovenous malformation phenotype. Three mutations were known, one was novel. In one patient, a somatic second hit was also identified. One index case had three affected children, illustrating that the mosaicism was also present in the germline."

PMID 30635911: "Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. "
Sources: Expert Review
Vascular Malformations_Somatic v0.9 GLMN Chris Richmond gene: GLMN was added
gene: GLMN was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLMN were set to 11845407
Phenotypes for gene: GLMN were set to Glomuvenous malformations (138000)
Penetrance for gene: GLMN were set to unknown
Review for gene: GLMN was set to GREEN
Added comment: Loss of function. Likely requires second hit for development of GVM: eg germline with second somatic hit (11845407)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond reviewed gene: AKT3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 22500628, 22729223; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (615937); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond Deleted their review
Vascular Malformations_Somatic v0.9 AKT3 Chris Richmond gene: AKT3 was added
gene: AKT3 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (615937)
Penetrance for gene: AKT3 were set to unknown
Mode of pathogenicity for gene: AKT3 was set to Other
Review for gene: AKT3 was set to GREEN
gene: AKT3 was marked as current diagnostic
Added comment: Gain of function. "De Novo Somatic Mutations in Components of the PI3K-AKT3-mTOR Pathway Cause Hemimegalencephaly" (PMID 22729223)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 ACVRL1 Chris Richmond gene: ACVRL1 was added
gene: ACVRL1 was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: ACVRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVRL1 were set to 21378382
Phenotypes for gene: ACVRL1 were set to Telangiectasia, hereditary hemorrhagic, type 2 (600376)
Penetrance for gene: ACVRL1 were set to unknown
Review for gene: ACVRL1 was set to GREEN
gene: ACVRL1 was marked as current diagnostic
Added comment: Primarily germline, but mosaic cases reported
Sources: Expert Review
Vascular Malformations_Somatic v0.9 ENG Chris Richmond gene: ENG was added
gene: ENG was added to Vascular Malformations_Somatic. Sources: Expert Review
Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENG were set to 21378382
Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 2 (600376)
Penetrance for gene: ENG were set to unknown
Review for gene: ENG was set to GREEN
Added comment: Primarily germline, but mosaic cases reported (21378382)
Sources: Expert Review
Vascular Malformations_Somatic v0.9 MTOR Bryony Thompson changed review comment from: Comment on list classification: Vascular malformations are not a prominent feature of the condition caused by germline variants in this gene. Somatic activating mutations are possibly associated with vascular malformations, thus this gene is not suitable for a germline testing panel.; to: Comment on list classification: Vascular malformations are not a prominent feature of the condition caused by germline variants in this gene. Somatic activating mutations are possibly associated with vascular malformations.
Vascular Malformations_Somatic v0.9 NRAS Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 MAP3K3 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 MAP2K1 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 KRAS Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 KRAS Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations are the cause of vascular malformations in this gene, thus it is not suitable to include on a germline testing panel.; to: Comment on list classification: Somatic activating mutations are the cause of vascular malformations in this gene.
Vascular Malformations_Somatic v0.9 HRAS Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations cause vascular malformations, which is not really appropriate for a germline testing panel; to: Comment on list classification: Somatic activating mutations cause vascular malformations.
Vascular Malformations_Somatic v0.9 GNAQ Bryony Thompson changed review comment from: Comment on list classification: Somatic mutation only causes vascular malformations. Not really suitable for a germline testing panel.; to: Comment on list classification: Somatic mutation only causes vascular malformations.
Vascular Malformations_Somatic v0.9 GNA14 Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations have only been reported to cause vascular malformations. This gene is not really suitable for a germline testing panel.; to: Comment on list classification: Somatic activating mutations have only been reported to cause vascular malformations.
Vascular Malformations_Somatic v0.9 GNA11 Bryony Thompson Deleted their comment
Vascular Malformations_Somatic v0.9 BRAF Bryony Thompson changed review comment from: Comment on list classification: Somatic activating mutations only are associated with vascular malformations. Not really suitable for a germline testing panel.; to: Comment on list classification: Somatic activating mutations only are associated with vascular malformations.
Vascular Malformations_Somatic v0.9 AKT1 Bryony Thompson changed review comment from: Comment on list classification: Somatic variants have been reported in association with vascular malformation. This gene is probably not suitable for a germline testing panel.; to: Comment on list classification: Somatic variants have been reported in association with vascular malformation.
Vascular Malformations_Somatic v0.9 KDR Zornitza Stark gene: KDR was added
gene: KDR was added to Vascular Malformations_Somatic. Sources: Expert list
Mode of inheritance for gene: KDR was set to Other
Publications for gene: KDR were set to 11807987; 18931684
Phenotypes for gene: KDR were set to Hemangioma, capillary infantile, somatic, MIM# 602089
Review for gene: KDR was set to RED
Added comment: Limited reports, may be susceptibility factor.
Sources: Expert list
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Classified gene: PIK3CA as Green List (high evidence)
Vascular Malformations_Somatic v0.8 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.7 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Vascular Malformations_Somatic. Sources: Expert list
Mode of inheritance for gene: PIK3CA was set to Other
Publications for gene: PIK3CA were set to 22729224; 23246288
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation (MCAP) syndrome; Cowden syndrome 5 615108
Mode of pathogenicity for gene: PIK3CA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PIK3CA was set to GREEN
Added comment: Somatic activating mutaitons are the main cause of vascular malformations, though note four individuals with germline variants have been reported, hence gene is on both somatic and germline panels.
Sources: Expert list
Vascular Malformations_Germline v0.96 Zornitza Stark Panel name changed from Inherited Vascular Malformations to Vascular Malformations_Germline
Vascular Malformations_Somatic v0.6 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Gene: sos1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Classified gene: SOS1 as Amber List (moderate evidence)
Vascular Malformations_Somatic v0.5 SOS1 Zornitza Stark Gene: sos1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Classified gene: PIK3R1 as Red List (low evidence)
Vascular Malformations_Somatic v0.4 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Marked gene: NRAS as ready
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.3 NRAS Zornitza Stark Tag somatic tag was added to gene: NRAS.
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Marked gene: MTOR as ready
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Classified gene: MTOR as Amber List (moderate evidence)
Vascular Malformations_Somatic v0.3 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Marked gene: MAP3K3 as ready
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Gene: map3k3 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 MAP3K3 Zornitza Stark Tag somatic tag was added to gene: MAP3K3.
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 MAP2K1 Zornitza Stark Tag somatic tag was added to gene: MAP2K1.
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Marked gene: KRAS as ready
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 KRAS Zornitza Stark Tag somatic tag was added to gene: KRAS.
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Marked gene: HRAS as ready
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 HRAS Zornitza Stark Tag somatic tag was added to gene: HRAS.
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNAQ Zornitza Stark Tag somatic tag was added to gene: GNAQ.
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Gene: gna14 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNA14 Zornitza Stark Tag somatic tag was added to gene: GNA14.
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Gene: gna11 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.2 GNA11 Zornitza Stark Phenotypes for gene: GNA11 were changed from Somatic hemangioma to Somatic hemangioma; Phacomatosis pigmentovascularis, somatic
Vascular Malformations_Somatic v0.1 GNA11 Zornitza Stark Tag somatic tag was added to gene: GNA11.
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Marked gene: BRAF as ready
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.1 BRAF Zornitza Stark Tag somatic tag was added to gene: BRAF.
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Marked gene: AKT1 as ready
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Gene: akt1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v0.1 AKT1 Zornitza Stark Tag somatic tag was added to gene: AKT1.
Vascular Malformations_Somatic v0.0 SOS1 Zornitza Stark gene: SOS1 was added
gene: SOS1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOS1 were set to 29907801
Phenotypes for gene: SOS1 were set to Noonan syndrome 4 610733
Vascular Malformations_Somatic v0.0 PIK3R1 Zornitza Stark gene: PIK3R1 was added
gene: PIK3R1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: PIK3R1 was set to Other
Publications for gene: PIK3R1 were set to 29174369
Phenotypes for gene: PIK3R1 were set to capillary and lymphatic malformation
Vascular Malformations_Somatic v0.0 NRAS Zornitza Stark gene: NRAS was added
gene: NRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: NRAS was set to Other
Publications for gene: NRAS were set to 30542204; 29461977
Phenotypes for gene: NRAS were set to Kaposiform lymphangiomatosis; Sporadic vascular malformation
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 MTOR Zornitza Stark gene: MTOR was added
gene: MTOR was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MTOR was set to Other
Publications for gene: MTOR were set to 29174369; 28892148
Phenotypes for gene: MTOR were set to Smith-Kingsmore syndrome 616638; Focal cortical dysplasia, type II, somatic 607341
Mode of pathogenicity for gene: MTOR was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 MAP3K3 Zornitza Stark gene: MAP3K3 was added
gene: MAP3K3 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MAP3K3 was set to Other
Publications for gene: MAP3K3 were set to 10700190; 25728774
Phenotypes for gene: MAP3K3 were set to Verrucous venous malformation
Vascular Malformations_Somatic v0.0 MAP2K1 Zornitza Stark gene: MAP2K1 was added
gene: MAP2K1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: MAP2K1 was set to Other
Publications for gene: MAP2K1 were set to 31486960; 28190454; 29461977
Phenotypes for gene: MAP2K1 were set to Arteriovenous malformation; Intramuscular fast-flow vascular anomaly
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 KRAS Zornitza Stark gene: KRAS was added
gene: KRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: KRAS was set to Other
Publications for gene: KRAS were set to 30677207; 30544177; 31160609
Phenotypes for gene: KRAS were set to Arteriovenous malformation of the brain, somatic 108010; Vascular malformation
Mode of pathogenicity for gene: KRAS was set to Other
Vascular Malformations_Somatic v0.0 HRAS Zornitza Stark gene: HRAS was added
gene: HRAS was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: HRAS was set to Other
Publications for gene: HRAS were set to 31160609; 31637524; 30208313
Phenotypes for gene: HRAS were set to Vascular malformation/overgrowth syndromes; Extracranial arteriovenous malformations
Mode of pathogenicity for gene: HRAS was set to Other
Vascular Malformations_Somatic v0.0 GNAQ Zornitza Stark gene: GNAQ was added
gene: GNAQ was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNAQ was set to Other
Publications for gene: GNAQ were set to 30920161
Phenotypes for gene: GNAQ were set to Sturge-Weber syndrome, somatic, mosaic 185300; Capillary malformations, congenital, 1, somatic, mosaic 163000; Phacomatosis pigmentovascularis
Vascular Malformations_Somatic v0.0 GNA14 Zornitza Stark gene: GNA14 was added
gene: GNA14 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNA14 was set to Other
Publications for gene: GNA14 were set to 31423605; 31707589; 27476652
Phenotypes for gene: GNA14 were set to Tufted angioma; vascular tumours; Anastomosing hemangioma
Mode of pathogenicity for gene: GNA14 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 GNA11 Zornitza Stark gene: GNA11 was added
gene: GNA11 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: GNA11 was set to Other
Publications for gene: GNA11 were set to 30677207
Phenotypes for gene: GNA11 were set to Somatic hemangioma
Mode of pathogenicity for gene: GNA11 was set to Other
Vascular Malformations_Somatic v0.0 BRAF Zornitza Stark gene: BRAF was added
gene: BRAF was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: BRAF was set to Other
Publications for gene: BRAF were set to 29316280; 30544177; 29461977
Phenotypes for gene: BRAF were set to Sporadic vascular malformations
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 AKT1 Zornitza Stark gene: AKT1 was added
gene: AKT1 was added to Vascular Malformations_Somatic. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: AKT1 was set to Other
Publications for gene: AKT1 were set to 23246288
Phenotypes for gene: AKT1 were set to Cowden syndrome 6 615109; Proteus syndrome, somatic 176920
Mode of pathogenicity for gene: AKT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Vascular Malformations_Somatic v0.0 Zornitza Stark Added panel Vascular Malformations_Somatic
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Marked gene: TMEM94 as ready
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Classified gene: TMEM94 as Green List (high evidence)
Congenital Heart Defect v0.52 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.51 TMEM94 Zornitza Stark gene: TMEM94 was added
gene: TMEM94 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies
Phenotypes for gene: TMEM94 were set to 30526868
Review for gene: TMEM94 was set to GREEN
Added comment: Ten individuals from 6 unrelated families reported, variety of congenital heart defects in addition to ID (ASD, VSD, Tetralogy of Fallot).
Sources: Expert list
Mendeliome v0.3202 SKIV2L Zornitza Stark changed review comment from: Multiple families reported with trichohepatoenteric syndrome.; to: Multiple families reported with trichohepatoenteric syndrome, agree unclear if ID is an association.
Mendeliome v0.3202 SKIV2L Zornitza Stark reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM# 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3202 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Mendeliome v0.3202 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Mendeliome v0.3202 SKIV2L Zornitza Stark Phenotypes for gene: SKIV2L were changed from to Trichohepatoenteric syndrome 2 614602; Intellectual disability
Mendeliome v0.3201 SKIV2L Zornitza Stark Publications for gene: SKIV2L were set to
Mendeliome v0.3200 SKIV2L Zornitza Stark Mode of inheritance for gene: SKIV2L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3199 NLRP5 Zornitza Stark Marked gene: NLRP5 as ready
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3199 NLRP5 Zornitza Stark Classified gene: NLRP5 as Amber List (moderate evidence)
Mendeliome v0.3199 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3198 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238
Phenotypes for gene: NLRP5 were set to Early embryonic arrest
Review for gene: NLRP5 was set to AMBER
Added comment: At least two families reported.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.138 Zornitza Stark removed gene:ACVR1 from the panel
Hereditary Neuropathy v0.67 EMILIN1 Zornitza Stark Marked gene: EMILIN1 as ready
Hereditary Neuropathy v0.67 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.67 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Hereditary Neuropathy v0.67 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.66 EMILIN1 Zornitza Stark gene: EMILIN1 was added
gene: EMILIN1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to 31978608; 26462740
Phenotypes for gene: EMILIN1 were set to Peripheral neuropathy; aortic aneurysm
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3197 EMILIN1 Zornitza Stark Marked gene: EMILIN1 as ready
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3197 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Amber List (moderate evidence)
Mendeliome v0.3197 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Marked gene: FOXE3 as ready
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Gene: foxe3 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.137 FOXE3 Zornitza Stark Phenotypes for gene: FOXE3 were changed from to {Aortic aneurysm, familial thoracic 11, susceptibility to}, MIM# 617349
Aortopathy_Connective Tissue Disorders v0.136 FOXE3 Zornitza Stark Classified gene: FOXE3 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.136 FOXE3 Zornitza Stark Gene: foxe3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3196 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Microcephaly v0.135 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Microcephaly v0.135 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.736 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Genetic Epilepsy v0.736 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Mendeliome v0.3195 HNRNPH1 Zornitza Stark gene: HNRNPH1 was added
gene: HNRNPH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Marked gene: HNRNPH1 as ready
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Gene: hnrnph1 has been classified as Green List (High Evidence).
Arthrogryposis v0.69 TPM2 Zornitza Stark Marked gene: TPM2 as ready
Arthrogryposis v0.69 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Arthrogryposis v0.69 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from to Arthrogryposis, distal, type 1A/2B4 (MIM#108120)
Arthrogryposis v0.68 TPM2 Zornitza Stark Publications for gene: TPM2 were set to
Arthrogryposis v0.67 TPM2 Zornitza Stark Mode of inheritance for gene: TPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3194 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability
Review for gene: PDCD6IP was set to AMBER
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Microcephaly v0.135 PDCD6IP Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models, upgrade to Amber.
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Marked gene: NME5 as ready
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3193 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Mendeliome v0.3193 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3192 NME5 Zornitza Stark gene: NME5 was added
gene: NME5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME5 were set to 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to AMBER
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Marked gene: NME5 as ready
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal model, upgrade to Amber.
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Classified gene: NME5 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.116 NME5 Zornitza Stark Gene: nme5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3191 ADAMTS19 Zornitza Stark Publications for gene: ADAMTS19 were set to 31844321
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Classified gene: ADAMTS19 as Green List (high evidence)
Mendeliome v0.3190 ADAMTS19 Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence).
Mendeliome v0.3189 ADAMTS19 Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3189 EMILIN1 Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Classified gene: AKT3 as Green List (high evidence)
Vascular Malformations_Germline v0.95 AKT3 Zornitza Stark Gene: akt3 has been classified as Green List (High Evidence).
Lymphoedema v0.3 ADAMTS3 Zornitza Stark Marked gene: ADAMTS3 as ready
Lymphoedema v0.3 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Lymphoedema v0.3 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Lymphoedema v0.3 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Lymphoedema v0.2 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Lymphoedema_syndromic. Sources: Expert Review
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families and functional data. Some dysmorphism described.
Sources: Expert Review
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Marked gene: ADAMTS3 as ready
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence)
Mendeliome v0.3189 ADAMTS3 Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence).
Mendeliome v0.3188 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families reported, supportive functional data.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Marked gene: GAA as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Added comment: Comment when marking as ready: Metabolic condition with phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Classified gene: GAA as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.50 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Marked gene: GNE as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Classified gene: GNE as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.49 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.66 FLNC Zornitza Stark Marked gene: FLNC as ready
Arthrogryposis v0.66 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Arthrogryposis v0.66 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Arthrogryposis v0.66 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Marked gene: COL12A1 as ready
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Gene: col12a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Classified gene: COL12A1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.135 COL12A1 Bryony Thompson Gene: col12a1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Marked gene: FLNC as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Added comment: Comment when marking as ready: Causes a range of conditions affecting muscle, phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.134 COL12A1 Bryony Thompson gene: COL12A1 was added
gene: COL12A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: COL12A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL12A1 were set to 28306229; 31273343; 24334604
Phenotypes for gene: COL12A1 were set to Myopathic EDS; Bethlem myopathy 2 MIM#616471; Ullrich congenital muscular dystrophy 2 MIM#616470
Review for gene: COL12A1 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
18 cases from 12 unrelated families have been reported with monoallelic variants (both de novo and inherited), and one family has been reported with a homozygous variant. A null mouse model recapitulates the phenotype.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.48 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Classified gene: LAMP2 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.47 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Marked gene: ETFDH as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Added comment: Comment when marking as ready: Metabolic disorder with phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Classified gene: ETFDH as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.46 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.45 DOK7 Zornitza Stark Classified gene: DOK7 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.45 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Marked gene: LMNA as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Classified gene: LMNA as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.44 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.43 LMNA Zornitza Stark Classified gene: LMNA as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.43 LMNA Zornitza Stark Gene: lmna has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Marked gene: CRYAB as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Gene: cryab has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.42 CRYAB Zornitza Stark Phenotypes for gene: CRYAB were changed from Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869 to Myopathy, myofibrillar, 2, MIM# 608810
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.41 CRYAB Zornitza Stark Mode of inheritance for gene: CRYAB 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
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.40 CRYAB Zornitza Stark Classified gene: CRYAB as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.40 CRYAB Zornitza Stark Gene: cryab has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 CRYAB Zornitza Stark reviewed gene: CRYAB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, myofibrillar, 2, MIM# 608810; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Marked gene: DES as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Added comment: Comment when marking as ready: Variable presentation, some overlap with LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Gene: des has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Classified gene: DES as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.39 DES Zornitza Stark Gene: des has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Marked gene: LPIN1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Gene: lpin1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.57 LPIN1 Zornitza Stark Publications for gene: LPIN1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.56 LPIN1 Zornitza Stark reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28649549, 18817903, 32410653; Phenotypes: Myoglobinuria, acute recurrent, autosomal recessive (MIM#268200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Gene: myh7 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Classified gene: MYH7 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.38 MYH7 Zornitza Stark Gene: myh7 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Marked gene: COL1A2 as ready
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Gene: col1a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Classified gene: COL1A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.133 COL1A2 Bryony Thompson Gene: col1a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.132 COL1A2 Bryony Thompson gene: COL1A2 was added
gene: COL1A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: COL1A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL1A2 were set to 28306229; 32091183; 2993307; 30821104
Phenotypes for gene: COL1A2 were set to Ehlers-Danlos syndrome, arthrochalasia type, 2 MIM#617821; Ehlers-Danlos syndrome, cardiac valvular type MIM#225320
Review for gene: COL1A2 was set to GREEN
gene: COL1A2 was marked as current diagnostic
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229). Monoallelic variants leading to (partial) loss of exon 6 are a well-established cause arthrochalasia type EDS.
Biallelic variant that lead to loss-of-function/absence of pro a2(I) collagen chains cause cardiac-valvular type EDS. 6 cases in 5 unrelated families have been reported with homozygous and compound heterozygous variants (PMID: 30821104).
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Marked gene: MYOT as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Added comment: Comment when marking as ready: Some of the reported variants have high population frequency.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Gene: myot has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Classified gene: MYOT as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.37 MYOT Zornitza Stark Gene: myot has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Marked gene: ORAI1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Gene: orai1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Classified gene: ORAI1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.36 ORAI1 Zornitza Stark Gene: orai1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ORAI1 Zornitza Stark reviewed gene: ORAI1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, tubular aggregate, 2 (MIM#615883); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v0.65 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Hereditary Neuropathy v0.65 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.65 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to
Hereditary Neuropathy v0.64 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Added comment: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; Changed publications: 24123876, 28633435, 28969388, 29982295, 32202298
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Added comment: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; Changed publications: 32202298
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Intellectual disability syndromic and non-syndromic v0.2723 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Changed publications: 24123876, 28633435, 28969388, 29982295, 32202298
Mendeliome v0.3187 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Mendeliome v0.3186 SP6 Zornitza Stark Marked gene: SP6 as ready
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3186 SP6 Zornitza Stark Classified gene: SP6 as Amber List (moderate evidence)
Mendeliome v0.3186 SP6 Zornitza Stark Gene: sp6 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v0.11 TBX5 Zornitza Stark Phenotypes for gene: TBX5 were changed from to Holt-Oram syndrome, MIM# 142900
Radial Ray Abnormalities v0.10 TBX5 Zornitza Stark Publications for gene: TBX5 were set to
Radial Ray Abnormalities v0.9 TBX5 Zornitza Stark Mode of inheritance for gene: TBX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Radial Ray Abnormalities v0.8 TBX5 Zornitza Stark reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 10077612, 31373354; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 TBX5 Zornitza Stark edited their review of gene: TBX5: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 TBX5 Zornitza Stark reviewed gene: TBX5: Rating: ; Mode of pathogenicity: None; Publications: 10077612; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.131 EFEMP2 Zornitza Stark Phenotypes for gene: EFEMP2 were changed from to Cutis laxa, autosomal recessive, type IB MIM# 614437
Aortopathy_Connective Tissue Disorders v0.130 FOXE3 Ain Roesley gene: FOXE3 was added
gene: FOXE3 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: FOXE3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXE3 were set to 30071989; 26854927
Review for gene: FOXE3 was set to AMBER
Added comment: PMID: 30071989; classification from “moderate” to “limited” after expert review, because the data provided are limited to single supporting publications with few HTAAD families.

Gene validity curation by ClinGen in 2016 was "moderate", citing segregation in the large family and animal models (https://search.clinicalgenome.org/kb/gene-validity/8261, PMID: 26854927)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.130 EFEMP2 Zornitza Stark Classified gene: EFEMP2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.130 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.129 EFEMP2 Paul De Fazio edited their review of gene: EFEMP2: Changed phenotypes: Cutis laxa, autosomal recessive, type IB MIM# 614437
Aortopathy_Connective Tissue Disorders v0.129 EFEMP2 Paul De Fazio gene: EFEMP2 was added
gene: EFEMP2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP2 were set to 20389311; 19664000; 16685658; 17937443; 22943132; 22440127
Review for gene: EFEMP2 was set to GREEN
gene: EFEMP2 was marked as current diagnostic
Added comment: Associated with cutis laxa in at least 6 unrelated individuals (PMID: 20389311; 19664000; 16685658; 17937443).

PMID: 22943132 reports 22 homozygous or compound het infants with: cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%).

Has also been associated with aortic dissection without presentation of cutis laxa (PMID: 22440127 - reports 9 affected individuals).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Classified gene: FBLN5 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.129 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.128 FBLN5 Zornitza Stark gene: FBLN5 was added
gene: FBLN5 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: FBLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBLN5 were set to 3232707; 22829427; 11805835
Phenotypes for gene: FBLN5 were set to Cutis laxa, autosomal recessive, type IA, MIM# 219100
Review for gene: FBLN5 was set to GREEN
Added comment: >3 families reported and functional data including mouse model.
Sources: Expert list
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.736 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.134 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Microcephaly v0.134 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.59 SMCHD1 Crystle Lee reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28067911, 31243061; Phenotypes: Bosma arhinia microphthalmia syndrome (MIM#603457); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.735 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Genetic Epilepsy v0.735 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.133 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Genetic Epilepsy v0.734 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Marked gene: DSE as ready
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Gene: dse has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Classified gene: DSE as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.126 DSE Bryony Thompson Gene: dse has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.125 DSE Bryony Thompson gene: DSE was added
gene: DSE was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: DSE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSE were set to 28306229; 23704329; 25703627; 32130795
Phenotypes for gene: DSE were set to Ehlers-Danlos syndrome, musculocontractural type 2 MIM#615539
Review for gene: DSE was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
8 cases from 6 unrelated families have been reported with homozygous variants.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Marked gene: MFAP5 as ready
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Classified gene: MFAP5 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.124 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2722 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Marked gene: ELN as ready
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.123 MFAP5 Paul De Fazio gene: MFAP5 was added
gene: MFAP5 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: MFAP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MFAP5 were set to 25434006; 30763214
Phenotypes for gene: MFAP5 were set to Aortic aneurysm, familial thoracic MIM# 616166
Review for gene: MFAP5 was set to AMBER
gene: MFAP5 was marked as current diagnostic
Added comment: 2 families described with thoracic aortic aneurysms and dissections, one with a nonsense variant and one with a missense (PMID:2544006). A recent review doesn't mention any other cases (PMID:30763214).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.123 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Aortopathy_Connective Tissue Disorders v0.123 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Classified gene: ELN as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.123 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.122 FKBP14 Bryony Thompson Classified gene: FKBP14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.122 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.122 CHST14 Zornitza Stark Classified gene: CHST14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.122 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Classified gene: FKBP14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Marked gene: FKBP14 as ready
Aortopathy_Connective Tissue Disorders v0.121 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.121 CHST14 Zornitza Stark Classified gene: CHST14 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.121 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson changed review comment from: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported.
Sources: Expert list; to: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported with this EDS subtype.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson edited their review of gene: FKBP14: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.120 FKBP14 Bryony Thompson gene: FKBP14 was added
gene: FKBP14 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: FKBP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP14 were set to 22265013; 28306229; 24773188; 27149304
Phenotypes for gene: FKBP14 were set to Ehlers-Danlos syndrome, kyphoscoliotic type, 2 MIM#614557
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 unrelated families with homozygous or compound heterozygous variants reported.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Marked gene: ATP6V0A2 as ready
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Classified gene: ATP6V0A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.119 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.118 NOTCH1 Zornitza Stark Phenotypes for gene: NOTCH1 were changed from Aortic valve disease MIM# 109730 to Aortic valve disease MIM# 109730; Thoracic aortic aneurysm
Aortopathy_Connective Tissue Disorders v0.117 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.117 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Classified gene: HNRNPH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Gene: hnrnph1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Classified gene: ALDH18A1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.116 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Marked gene: SMAD6 as ready
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Added comment: Comment when marking as ready: Primarily associated with aortic valve disease, but increased prevalence of thoracic aneurysm also documented.
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Gene: smad6 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Classified gene: SMAD6 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.115 SMAD6 Zornitza Stark Gene: smad6 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Marked gene: PLOD1 as ready
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Gene: plod1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Classified gene: PLOD1 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.114 PLOD1 Bryony Thompson Gene: plod1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Marked gene: PRDM5 as ready
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Gene: prdm5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Classified gene: PRDM5 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.113 PRDM5 Bryony Thompson Gene: prdm5 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.112 PRDM5 Bryony Thompson gene: PRDM5 was added
gene: PRDM5 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: PRDM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM5 were set to 28306229; 21664999
Phenotypes for gene: PRDM5 were set to Brittle cornea syndrome 2, MIM#614170
Review for gene: PRDM5 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229). Homozygous variants identified in at least 7 unrelated confirmed/likely consanguineous brittle cornea syndrome families. The mutation spectrum included stopgain, missense, splice site, and a large deletion.
Sources: Expert list
Skeletal dysplasia v0.34 ACVR1 Ain Roesley reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 19085907, 26776312, 18684712, 23572558, 20463014; Phenotypes: Fibrodysplasia ossificans progressiva (MIM# 135100); Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2720 HNRNPH1 Chirag Patel gene: HNRNPH1 was added
gene: HNRNPH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to PMID: 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1 ‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant.

2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Classified gene: ABCC6 as Red List (low evidence)
Aortopathy_Connective Tissue Disorders v0.111 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Marked gene: SLC39A13 as ready
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Gene: slc39a13 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Classified gene: SLC39A13 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.111 SLC39A13 Bryony Thompson Gene: slc39a13 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.110 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Marked gene: TNXB as ready
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Gene: tnxb has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Classified gene: TNXB as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.110 TNXB Bryony Thompson Gene: tnxb has been classified as Green List (High Evidence).
Arthrogryposis v0.65 TPM2 Crystle Lee reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30285720, 27726070, 24692096; Phenotypes: Arthrogryposis, distal, type 1A/2B4 (MIM#108120); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Marked gene: ZNF469 as ready
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Gene: znf469 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Classified gene: ZNF469 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.109 ZNF469 Bryony Thompson Gene: znf469 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2719 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.108 C1S Bryony Thompson Publications for gene: C1S were set to 30071989; 27745832; 31921203
Microcephaly v0.132 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Classified gene: C1S as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.107 C1S Bryony Thompson Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.106 ELN Belinda Chong gene: ELN was added
gene: ELN was added to Aortopathy_Connective Tissue Disorders. Sources: Other
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ELN were set to 27866049; 31560829; 19844261; 19844261
Phenotypes for gene: ELN were set to Cutis laxa 123700; Supravalvar aortic stenosis 185500
Review for gene: ELN was set to GREEN
Added comment: >3 families with Cutis laxa or Supravalvar aortic stenosis.

PMID: 30071989
Assertion made by the Aortopathy working group. So far there is no evidence that patients with ELN mutations present with aortic dissection or progressive aortic enlargement. Functional evidence, however, supports a role for ELN in HTAAD. ELN mutations cause AD cutis laxa syndrome, a disease with low risk for thoracic aortic disease and primarily diagnosed based on non-vascular features
Sources: Other
Ciliary Dyskinesia v0.115 NME5 Chirag Patel Mode of inheritance for gene: NME5 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.115 NME5 Chirag Patel Mode of inheritance for gene: NME5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.114 NME5 Chirag Patel Deleted their comment
Ciliary Dyskinesia v0.114 NME5 Chirag Patel edited their review of gene: NME5: Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.114 NME5 Chirag Patel gene: NME5 was added
gene: NME5 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: NME5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NME5 were set to PMID: 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to RED
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.106 CHST14 Ain Roesley gene: CHST14 was added
gene: CHST14 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to PMID: 28306229; 25703627; 26373698
Phenotypes for gene: CHST14 were set to Ehlers-Danlos syndrome, musculocontractural type 1 (MIM# 601776)
Review for gene: CHST14 was set to GREEN
Added comment: PMID: 28306229; one of the EDS genes recognised by the International EDS Consortium

PMID: 25703627, 5 individuals from 4 families
PMID: 26373698, 7 individuals from 4 families
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Marked gene: C1R as ready
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Gene: c1r has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.106 C1R Bryony Thompson Phenotypes for gene: C1R were changed from to Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080)
Aortopathy_Connective Tissue Disorders v0.105 C1R Bryony Thompson Publications for gene: C1R were set to
Aortopathy_Connective Tissue Disorders v0.104 C1R Bryony Thompson Mode of inheritance for gene: C1R was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.104 C1R Bryony Thompson Mode of inheritance for gene: C1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Classified gene: C1R as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.103 C1R Bryony Thompson Gene: c1r has been classified as Green List (High Evidence).
Congenital Heart Defect v0.50 ADAMTS19 Chirag Patel Classified gene: ADAMTS19 as Green List (high evidence)
Congenital Heart Defect v0.50 ADAMTS19 Chirag Patel Gene: adamts19 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.49 ADAMTS19 Chirag Patel reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Marked gene: B4GALT7 as ready
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Gene: b4galt7 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Classified gene: B4GALT7 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.102 B4GALT7 Bryony Thompson Gene: b4galt7 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.101 B4GALT7 Bryony Thompson gene: B4GALT7 was added
gene: B4GALT7 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: B4GALT7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT7 were set to 28306229; 26940150; 24755949; 23956117
Phenotypes for gene: B4GALT7 were set to Ehlers-Danlos syndrome with short stature and limb anomalies, 130070; Spondylodysplastic EDS
Review for gene: B4GALT7 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
At least 6 families reported with compound heterozygous or homozygous variants, with a spondylodysplastic EDS phenotype.
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.100 ATP6V0A2 Ain Roesley gene: ATP6V0A2 was added
gene: ATP6V0A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ATP6V0A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A2 were set to PMID: 23963297
Phenotypes for gene: ATP6V0A2 were set to Cutis laxa, autosomal recessive, type IIA (MIM# 219200), Wrinkly skin syndrome (MIM# 278250)
Penetrance for gene: ATP6V0A2 were set to unknown
Review for gene: ATP6V0A2 was set to GREEN
Added comment: PMID: 23963297; 6 patients from 5 unrelated families with cutis laxa

PMID: 30071989; not a gene for HTAAD by clingen working group
Sources: Literature
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond edited their review of gene: AKT3: Added comment: Established cause of Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937). Capillary malformations reported in PMID 23745724 & 22729224, both cases de novo AKT3 variants.; Changed rating: GREEN
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond Deleted their comment
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Marked gene: B3GALT6 as ready
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Gene: b3galt6 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.94 AKT3 Chris Richmond gene: AKT3 was added
gene: AKT3 was added to Inherited Vascular Malformations. Sources: Expert Review
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to 23745724; 22729224
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937)
Penetrance for gene: AKT3 were set to unknown
Mode of pathogenicity for gene: AKT3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Established cause of Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (615937). Capillary malformations reported in PMID 23745724 & 22729224, both cases de novo AKT3 variants.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Classified gene: B3GALT6 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.100 B3GALT6 Bryony Thompson Gene: b3galt6 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.99 B3GALT6 Bryony Thompson gene: B3GALT6 was added
gene: B3GALT6 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list
Mode of inheritance for gene: B3GALT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALT6 were set to 29931299; 28306229
Phenotypes for gene: B3GALT6 were set to Ehlers Danlos syndrome, progeroid type, 2, 615349; Spondylodysplastic EDS
Review for gene: B3GALT6 was set to GREEN
Added comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).
In 12 patients from 9 families with EDSSPD2, 8 compound heterozygous mutations and 1 homozygous mutation in B3GALT6 were identified, including 11 missense variants, 2 frameshift variants, a deletion of 19 amino acids, and a start codon alteration (PMID: 29931299).
Sources: Expert list
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Marked gene: ADAMTS2 as ready
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Gene: adamts2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.98 ADAMTS2 Bryony Thompson Publications for gene: ADAMTS2 were set to PMID: 30071989; 26765342
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Classified gene: ADAMTS2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)
Aortopathy_Connective Tissue Disorders v0.97 ADAMTS2 Bryony Thompson Gene: adamts2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.96 NOTCH1 Paul De Fazio gene: NOTCH1 was added
gene: NOTCH1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH1 were set to 16729972; 26820064; 16025100; 25963545
Phenotypes for gene: NOTCH1 were set to Aortic valve disease MIM# 109730
Review for gene: NOTCH1 was set to GREEN
Added comment: NOTCH1 variants are associated with cardiac abnormalities including aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, hypoplastic left heart syndrome, and thoracic aortic aneurysms in nonsyndromic individuals (2 families in PMID:16025100; 2 individuals in PMID:16729972; 14 families in PMID:26820064). Penetrance is incomplete and not all individuals display all phenotypes (e.g. only 6/63 individuals from PMID:26820064 had thoracic aortic aneurysms).

Monoallelic NOTCH1 variants are also responsible for Adams-Oliver syndrome, which can have associated cardiac abnormalities (PMID: 25963545).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 TNXB Paul De Fazio gene: TNXB was added
gene: TNXB was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: TNXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNXB were set to 28306229; 28306225; 23620400
Phenotypes for gene: TNXB were set to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408
Review for gene: TNXB was set to GREEN
gene: TNXB was marked as current diagnostic
Added comment: Association with classic Ehlers-Danlos syndrome is well-established (PMID:28306229;28306225).

Two families have also been described with Vesicoureteral Reflux caused by a heterozygous missense variant in this gene, some individuals were reported with asymptomatic joint hypermobility (PMID:23620400)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 PLOD1 Paul De Fazio gene: PLOD1 was added
gene: PLOD1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PLOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLOD1 were set to 28306225; 28306229
Phenotypes for gene: PLOD1 were set to Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400
Review for gene: PLOD1 was set to GREEN
gene: PLOD1 was marked as current diagnostic
Added comment: Review in PMID: 28306225 states: "A total of 139 mutations in PLOD1 have been identified in the 84 confirmed cases, of these there are 39 different mutations." It is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229).

Medium‐sized vessel rupture has been reported in several individual case reports.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 GAA Elena Savva gene: GAA was added
gene: GAA was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: GAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAA were set to PMID: 29880332
Phenotypes for gene: GAA were set to Glycogen storage disease II 232300
Review for gene: GAA was set to GREEN
Added comment: PMID: 29880332 - 16 adult patients (9 families) with Pombe disease. Proximal muscle weakness (12/16) and elevated CK were reported. Muscle biopsy showed vacuoles in 4/9 patients. Patients were described as having LGMD.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 GNE Crystle Lee gene: GNE was added
gene: GNE was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 22883483
Phenotypes for gene: GNE were set to Nonaka myopathy (MIM#605820)
Review for gene: GNE was set to AMBER
Added comment: Primarily a distal myopathy however proximal muscle weakness have also been reported. Limited evidence supporting LGMD phenotype.

PMID: 22883483: Half the patients reported with LGMD type proximal muscle weakness.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 SLC39A13 Paul De Fazio gene: SLC39A13 was added
gene: SLC39A13 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: SLC39A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A13 were set to 18985159; 18513683; 28306229; 28306225
Phenotypes for gene: SLC39A13 were set to Ehlers-Danlos syndrome, spondylodysplastic type, MIM# 612350
Review for gene: SLC39A13 was set to GREEN
gene: SLC39A13 was marked as current diagnostic
Added comment: 3 unrelated families described to date (PMID: 18985159;18513683). Is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229). See PMID: 28306225 for a review.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 ALDH18A1 Ain Roesley gene: ALDH18A1 was added
gene: ALDH18A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to PMID: 30071989; 26320891; 24913064; 18478038; 21739576; 22411858; 28228640
Phenotypes for gene: ALDH18A1 were set to Cutis laxa, autosomal dominant 3 (MIM# 616603); Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)
Review for gene: ALDH18A1 was set to GREEN
Added comment: PMID: 30071989; not a HTAAD gene by clingen working group

Cutis laxa, autosomal dominant 3 (MIM# 616603)

PMID: 28228640;
- Born to consanguineous parents and harbour a de novo missense p.(Arg126His). no functional done

PMID: 26320891;
- 8 unrelated individuals born to non-consanguineous families clinically diagnosed with de-barsy syndrome (DBS) or wrinkly skin syndrome. All variants occur at codon Arg138 and parental DNA from 6 probands confirmed de novo origin. (NOTE: table 1 states paternal origin however this is referring to the allele not variant (Figure S1)).
- Imaging of patients's cells showed increased accumulation of mutant protein at the mitochondrial outer membrane.
- Biochemical studies using patients' fibroblasts demonstrated LoF


Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)

PMID: 24913064;
- 2 patients from consanguineous families, 1x fs (c.2131del)+ 1x 1522bp del (resulting in exon 15 del)
- clinical features like facial dysmorphism, hypotonia, adducted thumbs and cutis laxa, which are frequently found in progeroid cutis laxa syndromes. In addition, they had cardiovascular abnormalities

PMID: 18478038;
- missense c.2350C>T; p.(His784Tyr) found in a a consanguineous New Zealand Maori family with 4 affecteds.
- patients' fibroblasts showed no defect in Proline accumulation

PMID: 21739576;
This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1 , c.1923 + 1G > A

PMID: 22411858;
pair of siblings chet for p.(Ser742Ile) and p.(Arg425Cys)
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 SMAD6 Paul De Fazio gene: SMAD6 was added
gene: SMAD6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMAD6 were set to 22275001; 28659821; 30963242; 30848080; 30796334
Phenotypes for gene: SMAD6 were set to Aortic valve disease 2 MIM# 614823
Review for gene: SMAD6 was set to AMBER
gene: SMAD6 was marked as current diagnostic
Added comment: Missense and LOF SMAD6 variants described as pathogenic or likely pathogenic have been identified in at least 20 individuals from bicuspid aortic valve/nonsyndromic thoracic aortic aneurysm cohorts (PMID:22275001, 30848080, 28659821, 30796334).

Functional studies on two of the missense variants supported abnormal function, but a third variant did not show any functional defect (and was also not well-conserved) (PMID:22275001).

Familial segregation studies in PMID: 30796334 demonstrated reduced penetrance (82%) and variable clinical expressivity, with coarctation of the aorta being a common comorbidity.

Biallelic variants have been decribed in 2 individuals with 'complex cardiac phenotype' (including aortic isthmus stenosis, dysplastic and stenotic pulmonary valve, and dilated cardiomyopathy) (PMID: 30963242).

There appears to be a clear gene-disease relationship but I am not sure if it belongs in this panel.
Sources: Literature
Arthrogryposis v0.65 FLNC Elena Savva gene: FLNC was added
gene: FLNC was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FLNC were set to PMID: 29858533
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524
Mode of pathogenicity for gene: FLNC was set to Other
Review for gene: FLNC was set to GREEN
Added comment: Myofibrillar myopathy - LOF
Distal myopathy - GOF
Cardiomyopathy, familial hypertrophic - LOF PTCs

PMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.
3/4 also presented with arthrogryposis
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 FLNC Elena Savva gene: FLNC was added
gene: FLNC was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FLNC were set to PMID: 29858533
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5 617047; Myopathy, distal, 4 614065; Myopathy, myofibrillar, 5 609524
Mode of pathogenicity for gene: FLNC was set to Other
Review for gene: FLNC was set to GREEN
Added comment: Myofibrillar myopathy - LOF
Distal myopathy - GOF
Cardiomyopathy, familial hypertrophic - LOF PTCs

PMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.
3/4 also presented with arthrogryposis
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LAMP2 Crystle Lee gene: LAMP2 was added
gene: LAMP2 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LAMP2 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: LAMP2 were set to 27179547; 22541782
Phenotypes for gene: LAMP2 were set to Danon disease (MIM#300257)
Review for gene: LAMP2 was set to AMBER
Added comment: Primarily presents as a cardiomyopathy condition, skeletal myopathy is less prominent and generally mild. Phenotypic overlap, proximal muscle weakness (85% of patients) (OMIM)

PMID: 27179547: 2 out of 7 affected members of 1 family presented with LGMD.

PMID: 22541782: Reported 2 patients. 1 patient presented with LGMD phenotype. EMG showed myopathic changes.
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ETFDH Elena Savva gene: ETFDH was added
gene: ETFDH was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to PMID: 19592060; 17412732
Phenotypes for gene: ETFDH were set to Glutaric acidemia IIC 231680
Review for gene: ETFDH was set to AMBER
Added comment: PMID: 19592060 - 1 adult patient reported with weakness in pelvic girdle muscles

PMID: 17412732 - 7 patients (5 families) with exercise intolerance and proximal myopathy with elevated CK levels. Onset ranged from childhood to adult-onset. Muscle histology in all five index cases revealed similar findings: moderate to severe myopathy with small vacuoles in most type 1 fibres. Patient also had subacute (3–6 months) exercise intolerance and proximal weakness affecting predominantly hip and shoulder girdle muscles.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 DOK7 Elena Savva gene: DOK7 was added
gene: DOK7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: DOK7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOK7 were set to PMID: 31453852; 32360404
Phenotypes for gene: DOK7 were set to Myasthenic syndrome, congenital, 10 254300
Review for gene: DOK7 was set to GREEN
Added comment: PMID: 31453852 - two adult patients with PTC variants and severe proximal muscle weakness with childhood onset. Condition is described as limb girdle myasthenia. Patient 1 had shoulder abduction and severe weakness of the pelvic girdle, patient 2 had muscle biopsy reveal muscle fibre II atrophy.

PMID: 32360404 - one adult patient with late onset atypical limb-girdle pattern of muscle weakness. Biopsy of deltoid muscle shows no features of MD.

PMID: 18626973 - 16 patients report proximal limb weakness, where 10 report neonatal onset.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LMNA Crystle Lee gene: LMNA was added
gene: LMNA was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNA were set to 27220833; 23746545; 17377071
Phenotypes for gene: LMNA were set to Emery-Dreifuss muscular dystrophy 2, autosomal dominant (MIM#181350)
Mode of pathogenicity for gene: LMNA was set to Other
Review for gene: LMNA was set to AMBER
Added comment: Phenotypic overlap, Formerly known as Limb-girdle muscular dystrophy 1B (LGMD1B) but has been reclassified as EDMD (OMIM)

PMID: 27220833: 1 late onset patient with LGMD

PMID: 23746545: Late onset patient with severe LGMD

PMID: 17377071: Later onset phenotypes may be associated with LoF while dominant negative variants result in childhood onset disease
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ADAMTS2 Ain Roesley gene: ADAMTS2 was added
gene: ADAMTS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ADAMTS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS2 were set to PMID: 30071989; 26765342
Phenotypes for gene: ADAMTS2 were set to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410)
Review for gene: ADAMTS2 was set to GREEN
Added comment: PMID: 30071989; not a gene for HTAAD by Clingen working group

PMID: 26765342;
5 patients form 4 unrelated families (3 PTVs + 1 exon del). qPCR of total RNA demonstrated significantly reduced ADAMTS2 expression and LoF was further supported by functional assays using dermal fibroblasts.
Authors noted that Family 1 and Patient 5 are clinically milder and hypothesised that their C-term variants may lead to some transcripts escaping NMD, producing a truncated yet partially functional protein.
Figure 2 provides an additional 6 previously reported variants (2 PTVs + 4 exon dels.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 CRYAB Elena Savva gene: CRYAB was added
gene: CRYAB was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CRYAB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CRYAB were set to PMID: 21337604; 32420686
Phenotypes for gene: CRYAB were set to Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869
Review for gene: CRYAB was set to AMBER
Added comment: PMID: 21337604 - 8 children with the same homozygous founder mutation and infantile onset muscular dystrophy. Truncal muscles reported to be more affected than limb muscles, phenotype was recapitulated in mouse models.

PMID: 32420686 - monozygotic twin boys with a heterozygous PTC mutation. Patients showed congenital hypotonia, slightly elevated CK levels. Focal signs of muscle degeneration were observed, no particular mention of the location of muscle weakness.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 DES Elena Savva gene: DES was added
gene: DES was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: DES was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DES were set to PMID: 20718792
Phenotypes for gene: DES were set to Myopathy, myofibrillar, 1 601419
Review for gene: DES was set to AMBER
Added comment: PMID: 20718792: large review of >100 patients. >70% had myopathy or muscle weakness, 67% presented with both distal and proximal muscle weakness.
Authors note myopathy generally begins with distal limbs, progressing later in life to proximal limb involvement.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 LPIN1 Crystle Lee gene: LPIN1 was added
gene: LPIN1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN1 were set to 28649549; 18817903; 32410653
Phenotypes for gene: LPIN1 were set to Myoglobinuria, acute recurrent, autosomal recessive (MIM#268200)
Review for gene: LPIN1 was set to AMBER
Added comment: Biallelic variants reported in>5 families. Rhabdomyolysis is a significant feature. Patients present with muscle weakness and elevated CK. Added as a differential diagnosis to LGMD (PanelApp UK)
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ACVR1 Ain Roesley gene: ACVR1 was added
gene: ACVR1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ACVR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVR1 were set to PMID: 30071989; 19085907; 26776312; 18684712; 23572558; 20463014
Phenotypes for gene: ACVR1 were set to Fibrodysplasia ossificans progressiva (MIM# 135100)
Review for gene: ACVR1 was set to AMBER
Added comment: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments.

PMID: 19085907; 112 FOP (classic and atypical) cases (104 sporadic and 8 families) with R206H has the recurrent variant and a greater clinical variability seen in non-R206H patients (PMID: 26776312)

PMID: 18684712, 23572558, 20463014; functional studies demonstrating GoF

PMID: 30071989; not a HTAAD gene by Clingen working group
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 MYH7 Crystle Lee gene: MYH7 was added
gene: MYH7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYH7 were set to 27387980; 20733148
Phenotypes for gene: MYH7 were set to Laing distal myopathy (MIM#160500); Scapuloperoneal syndrome, myopathic type (MIM#181430)
Mode of pathogenicity for gene: MYH7 was set to Other
Review for gene: MYH7 was set to AMBER
Added comment: Associated with a spectrum of skeletal myopathies which includes a scapuloperoneal or limb-girdle muscle form.
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 MYOT Crystle Lee gene: MYOT was added
gene: MYOT was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: MYOT was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYOT were set to 30055862; 21336781; 15947064
Phenotypes for gene: MYOT were set to Myopathy, myofibrillar, 3 (MIM#609200)
Review for gene: MYOT was set to AMBER
Added comment: Associated phenotype was previously known as LGMD1/LGMD1A (OMIM; PMID: 30055862). Phenotypic overlap.

PMID: 21336781: Reported a severe case of LGMD. Patient presented with late onset progressive proximal muscle weakness. CK was slightly elevated. Authors concluded that gene is a rare cause of adult onset LGMD. Variant present in gnomAD (12 hets).

PMID: 15947064: 5 variants reported in 13 patients (including 3 families). Late onset, EMG showed myopathic changes in most patients. Highest MAF (10 hets in gnomAD; Ser60Phe). 9/13 did not show elevated CK levels.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v0.96 ZNF469 Paul De Fazio edited their review of gene: ZNF469: Changed phenotypes: Brittle cornea syndrome 1 MIM# 229200
Aortopathy_Connective Tissue Disorders v0.96 ZNF469 Paul De Fazio gene: ZNF469 was added
gene: ZNF469 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ZNF469 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF469 were set to 28306229; 28306225
Phenotypes for gene: ZNF469 were set to Brittle cornea syndrome 1
Review for gene: ZNF469 was set to GREEN
gene: ZNF469 was marked as current diagnostic
Added comment: Association with brittle cornea syndrome (BCS) is well-established. 32 patients with variants in ZNF469 and BCS are reviewed in PMID: 28306225.

BCS is classified as a form of Ehlers-Danlos syndrome (PMID: 28306229).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.96 ABCC6 Ain Roesley gene: ABCC6 was added
gene: ABCC6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC6 were set to PMID: 30071989; 11536079
Phenotypes for gene: ABCC6 were set to Pseudoxanthoma elasticum (MIM# 264800)
Review for gene: ABCC6 was set to AMBER
Added comment: PMID: 30071989; not a gene for Heritable Thoracic Aortic Aneurysm and Dissection by Clingen Working Group

PMID: 11536079; a cohort of 122 PXE patients were sequenced and 36 different variants were reported
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 ORAI1 Crystle Lee gene: ORAI1 was added
gene: ORAI1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ORAI1 were set to 31448844
Phenotypes for gene: ORAI1 were set to Myopathy, tubular aggregate, 2 (MIM#615883)
Review for gene: ORAI1 was set to AMBER
Added comment: OMIM notes both proximal and diffuse muscle weakness. There is some phenotypic overlap.

PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
Sources: Expert Review
Mendeliome v0.3185 MCM3AP Eleanor Williams changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Mendeliome v0.3185 MCM3AP Eleanor Williams reviewed gene: MCM3AP: Rating: ; Mode of pathogenicity: None; Publications: 32202298; Phenotypes: peripheral neuropathy with or without impaired intellectual development MIM#618124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3185 SP6 Eleanor Williams gene: SP6 was added
gene: SP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta
Review for gene: SP6 was set to AMBER
Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 )
Sources: Literature
Mendeliome v0.3185 TBX5 Eleanor Williams reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31373354; Phenotypes: Holt-Oram syndrome; Mode of inheritance: None
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v0.8 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to Aniridia MIM# 106210; Anterior segment dysgenesis 5, multiple subtypes MIM# 6042293; Cataract with late-onset corneal dystrophy MIM# 106210; Foveal hypoplasia 1 MIM# 136520; Keratitis MIM# 148190; Optic nerve hypoplasia MIM# 165550
Eye Anterior Segment Abnormalities v0.7 PAX6 Zornitza Stark Publications for gene: PAX6 were set to
Eye Anterior Segment Abnormalities v0.6 PAX6 Zornitza Stark Mode of inheritance for gene: PAX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 MYH8 Zornitza Stark Marked gene: MYH8 as ready
Mendeliome v0.3185 MYH8 Zornitza Stark Added comment: Comment when marking as ready: Recurrent variant p.R674Q has occurred de novo in at least some families.
Mendeliome v0.3185 MYH8 Zornitza Stark Gene: myh8 has been classified as Green List (High Evidence).
Mendeliome v0.3185 MYH8 Zornitza Stark Phenotypes for gene: MYH8 were changed from to Trismus-pseudocamptodactyly syndrome MIM# 158300; Carney complex variant MIM# 608837
Mendeliome v0.3184 MYH8 Zornitza Stark Publications for gene: MYH8 were set to
Mendeliome v0.3183 MYH8 Zornitza Stark Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Marked gene: ATP6V1A as ready
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Gene: atp6v1a has been classified as Green List (High Evidence).
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Classified gene: ATP6V1A as Green List (high evidence)
Cutis Laxa v0.5 ATP6V1A Bryony Thompson Gene: atp6v1a has been classified as Green List (High Evidence).
Cutis Laxa v0.4 ATP6V1A Bryony Thompson gene: ATP6V1A was added
gene: ATP6V1A was added to Cutis Laxa. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to 28065471
Phenotypes for gene: ATP6V1A were set to Cutis laxa, autosomal recessive, type IID MIM#617403
Review for gene: ATP6V1A was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (G72D, R338C), with supportive molecular analyses of patient cells.
Sources: Literature
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Marked gene: ATP6V1E1 as ready
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Classified gene: ATP6V1E1 as Green List (high evidence)
Cutis Laxa v0.3 ATP6V1E1 Bryony Thompson Gene: atp6v1e1 has been classified as Green List (High Evidence).
Cutis Laxa v0.2 ATP6V1E1 Bryony Thompson gene: ATP6V1E1 was added
gene: ATP6V1E1 was added to Cutis Laxa. Sources: Expert list
Mode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1E1 were set to 28065471; 27023906
Phenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC MIM#617402
Review for gene: ATP6V1E1 was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular anlayses of patient tissues was supportive.
Sources: Expert list
Mendeliome v0.3182 MYH8 Teresa Zhao reviewed gene: MYH8: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28377322, 18049072, 17041932; Phenotypes: Trismus-pseudocamptodactyly syndrome MIM# 158300, Carney complex variant MIM# 608837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Eye Anterior Segment Abnormalities v0.5 PAX6 Teresa Zhao changed review comment from: Loss of function is a well established mechanism.

This protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).

Exon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).

PAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different gens (PMID: 26899008).
isoform a: induces KRT3 expression.
isoform b: indluced KRT12 expression when combined with KLF4 and OCT4.; to: Loss of function is a well established mechanism.

This protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).

Exon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).

PAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different genes (PMID: 26899008).
isoform a: induces KRT3 expression.
isoform b: indluced KRT12 expression when combined with KLF4 and OCT4.
Eye Anterior Segment Abnormalities v0.5 PAX6 Teresa Zhao reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27081561, 20132240, 26899008; Phenotypes: ?Coloboma of optic nerve MIM# 120430, ?Coloboma, ocular MIM# 120200, ?Morning glory disc anomaly MIM# 120430, Aniridia MIM# 106210, Anterior segment dysgenesis 5, multiple subtypes MIM# 6042293, Cataract with late-onset corneal dystrophy MIM# 106210, Foveal hypoplasia 1 MIM# 136520, Keratitis MIM# 148190, Optic nerve hypoplasia MIM# 165550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3182 SKIV2L Sarah Leigh reviewed gene: SKIV2L: Rating: AMBER; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: Intellectual disability; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Marked gene: PFKM as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Gene: pfkm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Classified gene: PFKM as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.35 PFKM Zornitza Stark Gene: pfkm has been classified as Amber List (Moderate Evidence).
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Marked gene: PFKM as ready
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.11 PFKM Zornitza Stark Phenotypes for gene: PFKM were changed from to Glycogen storage disease VII (MIM#232800)
Glycogen Storage Diseases v0.10 PFKM Zornitza Stark Publications for gene: PFKM were set to
Glycogen Storage Diseases v0.9 PFKM Zornitza Stark Mode of inheritance for gene: PFKM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Marked gene: POMK as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).