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Unexplained young onset end-stage renal disease v4.3 IFT140 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: IFT140.
Unexplained young onset end-stage renal disease v4.3 HPRT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HPRT1.
Unexplained young onset end-stage renal disease v4.3 HNF4A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HNF4A.
Unexplained young onset end-stage renal disease v4.3 GSN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GSN.
Unexplained young onset end-stage renal disease v4.3 GON7 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GON7.
Unexplained young onset end-stage renal disease v4.3 GNA11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: GNA11.
Unexplained young onset end-stage renal disease v4.3 FN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FN1.
Unexplained young onset end-stage renal disease v4.3 FLCN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FLCN.
Unexplained young onset end-stage renal disease v4.3 FGA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FGA.
Unexplained young onset end-stage renal disease v4.3 FAM20A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAM20A.
Unexplained young onset end-stage renal disease v4.3 FAH Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FAH.
Unexplained young onset end-stage renal disease v4.3 DLG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG5.
Unexplained young onset end-stage renal disease v4.3 DAAM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DAAM2.
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CYP24A1.
Unexplained young onset end-stage renal disease v4.3 CUL3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CUL3.
Unexplained young onset end-stage renal disease v4.3 CNNM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CNNM2.
Unexplained young onset end-stage renal disease v4.3 CLDN19 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN19.
Unexplained young onset end-stage renal disease v4.3 CLDN16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN16.
Unexplained young onset end-stage renal disease v4.3 CLDN10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN10.
Unexplained young onset end-stage renal disease v4.3 CLCNKB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCNKB.
Unexplained young onset end-stage renal disease v4.3 CFHR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CFHR2.
Unexplained young onset end-stage renal disease v4.3 CD151 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CD151.
Unexplained young onset end-stage renal disease v4.3 CASR Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASR.
Unexplained young onset end-stage renal disease v4.3 CA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CA2.
Unexplained young onset end-stage renal disease v4.3 AVPR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AVPR2.
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V1B1.
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP6V0A4.
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP1A1.
Unexplained young onset end-stage renal disease v4.3 APRT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APRT.
Unexplained young onset end-stage renal disease v4.3 APOE Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOE.
Unexplained young onset end-stage renal disease v4.3 APOC2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOC2.
Unexplained young onset end-stage renal disease v4.3 APOA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA2.
Unexplained young onset end-stage renal disease v4.3 APOA1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: APOA1.
Unexplained young onset end-stage renal disease v4.3 AP2S1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AP2S1.
Unexplained young onset end-stage renal disease v4.3 ALG9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG9.
Unexplained young onset end-stage renal disease v4.3 ALG8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG8.
Unexplained young onset end-stage renal disease v4.3 ALG5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ALG5.
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Unexplained young onset end-stage renal disease v4.3 YRDC Arina Puzriakova reviewed gene: YRDC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 WNK4 Arina Puzriakova reviewed gene: WNK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 WDR72 Arina Puzriakova reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TULP3 Arina Puzriakova reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TTR Arina Puzriakova reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 TRPM6 Arina Puzriakova reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 TPRKB Arina Puzriakova reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 STRADA Arina Puzriakova reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC5A2 Arina Puzriakova reviewed gene: SLC5A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A4 Arina Puzriakova reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC4A1 Arina Puzriakova reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A3 Arina Puzriakova reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC34A1 Arina Puzriakova reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC2A2 Arina Puzriakova reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A3 Arina Puzriakova reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SLC12A1 Arina Puzriakova reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SEC63 Arina Puzriakova reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 SCNN1G Arina Puzriakova reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1B Arina Puzriakova reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SCNN1A Arina Puzriakova reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 SARS2 Arina Puzriakova reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 RRAGD Arina Puzriakova reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 RMND1 Arina Puzriakova reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 PRKCSH Arina Puzriakova reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 PHEX Arina Puzriakova reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Unexplained young onset end-stage renal disease v4.3 PDSS2 Arina Puzriakova reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 NR3C2 Arina Puzriakova reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 MOCOS Arina Puzriakova reviewed gene: MOCOS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 MAGED2 Arina Puzriakova reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 LYZ Arina Puzriakova reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 LCAT Arina Puzriakova reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KLHL3 Arina Puzriakova reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ16 Arina Puzriakova reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ10 Arina Puzriakova reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 KCNJ1 Arina Puzriakova reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT27 Arina Puzriakova reviewed gene: IFT27: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT172 Arina Puzriakova reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 IFT140 Arina Puzriakova reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 HPRT1 Arina Puzriakova reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Unexplained young onset end-stage renal disease v4.3 HNF4A Arina Puzriakova reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 GSN Arina Puzriakova reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GON7 Arina Puzriakova reviewed gene: GON7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 GNA11 Arina Puzriakova reviewed gene: GNA11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FN1 Arina Puzriakova reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FLCN Arina Puzriakova reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FGA Arina Puzriakova reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 FAM20A Arina Puzriakova reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 FAH Arina Puzriakova reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DLG5 Arina Puzriakova reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 DAAM2 Arina Puzriakova reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CYP24A1 Arina Puzriakova reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CUL3 Arina Puzriakova reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 CNNM2 Arina Puzriakova reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN19 Arina Puzriakova reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN16 Arina Puzriakova reviewed gene: CLDN16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLDN10 Arina Puzriakova reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CLCNKB Arina Puzriakova reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CFHR2 Arina Puzriakova reviewed gene: CFHR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CD151 Arina Puzriakova reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CASR Arina Puzriakova reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 CA2 Arina Puzriakova reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 AVPR2 Arina Puzriakova reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Unexplained young onset end-stage renal disease v4.3 ATP6V1B1 Arina Puzriakova reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP6V0A4 Arina Puzriakova reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ATP1A1 Arina Puzriakova reviewed gene: ATP1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APRT Arina Puzriakova reviewed gene: APRT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 APOE Arina Puzriakova reviewed gene: APOE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOC2 Arina Puzriakova reviewed gene: APOC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA2 Arina Puzriakova reviewed gene: APOA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 APOA1 Arina Puzriakova reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 AP2S1 Arina Puzriakova reviewed gene: AP2S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v4.3 ALG9 Arina Puzriakova reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v4.3 ALG8 Arina Puzriakova reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.3 ALG5 Arina Puzriakova reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Unexplained young onset end-stage renal disease v4.2 YRDC Achchuthan Shanmugasundram Source Expert Review Green was added to YRDC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WNK4 Achchuthan Shanmugasundram Source Expert Review Green was added to WNK4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 WDR72 Achchuthan Shanmugasundram Source Expert Review Green was added to WDR72.
Source NHS GMS was added to WDR72.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TULP3 Achchuthan Shanmugasundram Source Expert Review Green was added to TULP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TTR Achchuthan Shanmugasundram Source Expert Review Green was added to TTR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TRPM6 Achchuthan Shanmugasundram Source Expert Review Green was added to TRPM6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 TPRKB Achchuthan Shanmugasundram Source Expert Review Green was added to TPRKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 STRADA Achchuthan Shanmugasundram Source Expert Review Green was added to STRADA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC5A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC5A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A4 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC4A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC34A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC34A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC2A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SLC12A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC12A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SEC63 Achchuthan Shanmugasundram Source Expert Review Green was added to SEC63.
Source NHS GMS was added to SEC63.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1G Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1G.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1B Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SCNN1A Achchuthan Shanmugasundram Source Expert Review Green was added to SCNN1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 SARS2 Achchuthan Shanmugasundram Source Expert Review Green was added to SARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RRAGD Achchuthan Shanmugasundram Source Expert Review Green was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 RMND1 Achchuthan Shanmugasundram Source Expert Review Green was added to RMND1.
Source NHS GMS was added to RMND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PRKCSH Achchuthan Shanmugasundram Source Expert Review Green was added to PRKCSH.
Source NHS GMS was added to PRKCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PHEX Achchuthan Shanmugasundram Source Expert Review Green was added to PHEX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 PDSS2 Achchuthan Shanmugasundram Source Expert Review Green was added to PDSS2.
Source NHS GMS was added to PDSS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 NR3C2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR3C2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MOCOS Achchuthan Shanmugasundram Source Expert Review Green was added to MOCOS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 MAGED2 Achchuthan Shanmugasundram Source Expert Review Green was added to MAGED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LYZ Achchuthan Shanmugasundram Source Expert Review Green was added to LYZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 LCAT Achchuthan Shanmugasundram Source Expert Review Green was added to LCAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KLHL3 Achchuthan Shanmugasundram Source Expert Review Green was added to KLHL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ16 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ10 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 KCNJ1 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNJ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT27 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT27.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT172 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT172.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 IFT140 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HPRT1 Achchuthan Shanmugasundram Source Expert Review Green was added to HPRT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 HNF4A Achchuthan Shanmugasundram Source Expert Review Green was added to HNF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GSN Achchuthan Shanmugasundram Source Expert Review Green was added to GSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GON7 Achchuthan Shanmugasundram Source Expert Review Green was added to GON7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 GNA11 Achchuthan Shanmugasundram Source Expert Review Green was added to GNA11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FN1 Achchuthan Shanmugasundram Source Expert Review Green was added to FN1.
Source NHS GMS was added to FN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FLCN Achchuthan Shanmugasundram Source Expert Review Green was added to FLCN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FGA Achchuthan Shanmugasundram Source Expert Review Green was added to FGA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAM20A Achchuthan Shanmugasundram Source Expert Review Green was added to FAM20A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 FAH Achchuthan Shanmugasundram Source Expert Review Green was added to FAH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DLG5 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 DAAM2 Achchuthan Shanmugasundram Source Expert Review Green was added to DAAM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CYP24A1 Achchuthan Shanmugasundram Source Expert Review Green was added to CYP24A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CUL3 Achchuthan Shanmugasundram Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CNNM2 Achchuthan Shanmugasundram Source Expert Review Green was added to CNNM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN19 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN16 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLDN10 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CLCNKB Achchuthan Shanmugasundram Source Expert Review Green was added to CLCNKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CFHR2 Achchuthan Shanmugasundram Source Expert Review Green was added to CFHR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CD151 Achchuthan Shanmugasundram Source Expert Review Green was added to CD151.
Source NHS GMS was added to CD151.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CASR Achchuthan Shanmugasundram Source Expert Review Green was added to CASR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 CA2 Achchuthan Shanmugasundram Source Expert Review Green was added to CA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AVPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to AVPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V1B1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V1B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP6V0A4 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ATP1A1 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP1A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APRT Achchuthan Shanmugasundram Source Expert Review Green was added to APRT.
Source NHS GMS was added to APRT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOE Achchuthan Shanmugasundram Source Expert Review Green was added to APOE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOC2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA2 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 APOA1 Achchuthan Shanmugasundram Source Expert Review Green was added to APOA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 AP2S1 Achchuthan Shanmugasundram Source Expert Review Green was added to AP2S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG9 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG8 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v4.2 ALG5 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v3.3 AMBN Claire Smith edited their review of gene: AMBN: Added comment: PMID: 38058155 identifies AMBN variants that appear to cause disease in an autosomal dominant fashion.
One family has a dominant family history spanning 4 generations, and the likely causative variant in this family was also identified as monoallelic/heterozygous in 2 other apparently unrelated individuals with isolated AI.; Changed publications to: PMID: 24858907, 26502894, 38058155; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 SMG8 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SMG8.
Tag Q4_23_NHS_review was removed from gene: SMG8.
Structural eye disease v3.79 SLC25A24 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SLC25A24.
Tag Q4_23_NHS_review was removed from gene: SLC25A24.
Structural eye disease v3.79 RHOA Arina Puzriakova Tag Q4_23_promote_green was removed from gene: RHOA.
Tag Q4_23_NHS_review was removed from gene: RHOA.
Structural eye disease v3.79 OFD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: OFD1.
Tag Q3_23_NHS_review was removed from gene: OFD1.
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.11 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.79 NUP188 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NUP188.
Tag Q4_23_NHS_review was removed from gene: NUP188.
Structural eye disease v3.79 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Classified gene: CDH1 as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v2.10 CDH1 Achchuthan Shanmugasundram Gene: cdh1 has been classified as Red List (Low Evidence).
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CDH1.
Tag Q3_23_expert_review was removed from gene: CDH1.
Structural eye disease v3.79 KIF11 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIF11.
Tag Q4_23_NHS_review was removed from gene: KIF11.
Structural eye disease v3.79 KIAA0586 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KIAA0586.
Tag Q4_23_NHS_review was removed from gene: KIAA0586.
Structural eye disease v3.79 KDM6A Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KDM6A.
Tag Q4_23_NHS_review was removed from gene: KDM6A.
Structural eye disease v3.79 EPHA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: EPHA2.
Tag Q4_23_MOI was removed from gene: EPHA2.
Tag Q4_23_NHS_review was removed from gene: EPHA2.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith changed review comment from: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review; to: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review

Personal communication with Roland Friedel and Christian Junquiera-Alves regarding their findings in their Plxnb2-/- mouse model after publication of human patients with PLXNB2 variants: "We had made also initial observations in the PB2 KO mouse on cochlear defects and tooth malformations that looked interesting, but we did not follow up as I focused on cerebellar development. Now these findings look in retrospect much more exciting considering your data."
Structural eye disease v3.79 CRYBB2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CRYBB2.
Tag Q4_23_NHS_review was removed from gene: CRYBB2.
Structural eye disease v3.79 BMPR1B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BMPR1B.
Tag Q4_23_NHS_review was removed from gene: BMPR1B.
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARHGAP35.
Tag Q4_23_NHS_review was removed from gene: ARHGAP35.
Structural eye disease v3.79 ANK3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ANK3.
Tag Q4_23_NHS_review was removed from gene: ANK3.
Structural eye disease v3.79 ALX1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ALX1.
Tag Q3_23_NHS_review was removed from gene: ALX1.
Structural eye disease v3.79 SMG8 Arina Puzriakova reviewed gene: SMG8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 SLC25A24 Arina Puzriakova reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 RHOA Arina Puzriakova reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v3.79 OFD1 Arina Puzriakova reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 NUP188 Arina Puzriakova reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIF11 Arina Puzriakova reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 KIAA0586 Arina Puzriakova reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.79 KDM6A Arina Puzriakova reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Structural eye disease v3.79 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v3.79 CRYBB2 Arina Puzriakova reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 BMPR1B Arina Puzriakova reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ARHGAP35 Arina Puzriakova reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ANK3 Arina Puzriakova reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.79 ALX1 Arina Puzriakova reviewed gene: ALX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.78 SMG8 Arina Puzriakova Source NHS GMS was added to SMG8.
Source Expert Review Green was added to SMG8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 SLC25A24 Arina Puzriakova Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 RHOA Arina Puzriakova Source NHS GMS was added to RHOA.
Source Expert Review Green was added to RHOA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 OFD1 Arina Puzriakova Source Expert Review Green was added to OFD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 NUP188 Arina Puzriakova Source NHS GMS was added to NUP188.
Source Expert Review Green was added to NUP188.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIF11 Arina Puzriakova Source Expert Review Green was added to KIF11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KIAA0586 Arina Puzriakova Source NHS GMS was added to KIAA0586.
Source Expert Review Green was added to KIAA0586.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 KDM6A Arina Puzriakova Source Expert Review Green was added to KDM6A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 EPHA2 Arina Puzriakova Source Expert Review Green was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 CRYBB2 Arina Puzriakova Source Expert Review Green was added to CRYBB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 BMPR1B Arina Puzriakova Source NHS GMS was added to BMPR1B.
Source Expert Review Green was added to BMPR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ARHGAP35 Arina Puzriakova Source NHS GMS was added to ARHGAP35.
Source Expert Review Green was added to ARHGAP35.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v3.78 ALX1 Arina Puzriakova Source Expert Review Green was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATRIP.
Tag Q4_23_expert_review was removed from gene: ATRIP.
Amelogenesis imperfecta v3.3 PLXNB2 Claire Smith gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature,Expert Review
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta; sensorineural hearing loss
Penetrance for gene: PLXNB2 were set to unknown
Review for gene: PLXNB2 was set to GREEN
Added comment: PMID: 38458752 Smith et al. (in press) report 8 patients in 6 families with rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and sensorineural hearing loss as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases.
Sources: Literature, Expert Review
Breast cancer pertinent cancer susceptibility v2.9 CDH1 Arina Puzriakova edited their review of gene: CDH1: Added comment: After NHS Genomic Medicine Service consideration, this gene has not been made Green and has been rated as Red. Additional comments from reviewing GLHs: 'There is a well established association of this gene withpredisposition to lobular breast cancer, but it presents huge problems when it is identified outside the context of a relevant family history. The UK Cancer genetics community do not want to add this gene to any general breast cancer susceptibility panels hence are extremely reluctant to test this gene outside of the already existing R215 criteria'; Changed rating: RED; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v2.9 ATRIP Arina Puzriakova edited their review of gene: ATRIP: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: 'Whilst the referenced paper does support an association with breast cancer, more studies are needed before we can consider adding this gene to any panel. The referenced paper itself comments that further replication in larger datasets is necessary to provide figures on lifetime risk, to better define the association with breast cancer and the clinic-pathological characteristics of tumors in variant carriers . Without this important information, it is too early to add the gene to a breast cancer susceptibility panel'; Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.4 RPE65 Arina Puzriakova Tag Q4_23_MOI was removed from gene: RPE65.
Retinal disorders v5.4 PYGM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: PYGM.
Tag Q3_23_NHS_review was removed from gene: PYGM.
Retinal disorders v5.4 NBAS Arina Puzriakova Tag Q3_23_promote_green was removed from gene: NBAS.
Tag Q3_23_NHS_review was removed from gene: NBAS.
Retinal disorders v5.4 MVK Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MVK.
Tag Q4_23_NHS_review was removed from gene: MVK.
Retinal disorders v5.4 MPDZ Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MPDZ.
Tag Q3_23_NHS_review was removed from gene: MPDZ.
Retinal disorders v5.4 MIR204 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MIR204.
Tag Q3_23_NHS_review was removed from gene: MIR204.
Retinal disorders v5.4 MCOLN1 Arina Puzriakova Phenotypes for gene: MCOLN1 were changed from to Mucolipidosis IV, OMIM:252650
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: MCOLN1.
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DYNC2H1.
Retinal disorders v5.3 CTNND1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CTNND1.
Retinal disorders v5.3 CFAP20 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CFAP20.
Retinal disorders v5.3 RPE65 Arina Puzriakova Mode of inheritance for gene RPE65 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.3 PYGM Arina Puzriakova Source NHS GMS was added to PYGM.
Source Expert Review Green was added to PYGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 NBAS Arina Puzriakova Source Expert Review Green was added to NBAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MVK Arina Puzriakova Source Expert Review Green was added to MVK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MPDZ Arina Puzriakova Source NHS GMS was added to MPDZ.
Source Expert Review Green was added to MPDZ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MIR204 Arina Puzriakova Source Expert Review Green was added to MIR204.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 MCOLN1 Arina Puzriakova Source NHS GMS was added to MCOLN1.
Source Expert Review Green was added to MCOLN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 DYNC2H1 Arina Puzriakova Source NHS GMS was added to DYNC2H1.
Source Expert Review Green was added to DYNC2H1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CTNND1 Arina Puzriakova Source NHS GMS was added to CTNND1.
Source Expert Review Green was added to CTNND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.3 CFAP20 Arina Puzriakova Source NHS GMS was added to CFAP20.
Source Expert Review Green was added to CFAP20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v5.2 RPE65 Arina Puzriakova edited their review of gene: RPE65: Added comment: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v5.2 PYGM Arina Puzriakova reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 NBAS Arina Puzriakova reviewed gene: NBAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MVK Arina Puzriakova reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MPDZ Arina Puzriakova reviewed gene: MPDZ: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 MIR204 Arina Puzriakova reviewed gene: MIR204: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 MCOLN1 Arina Puzriakova reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 DYNC2H1 Arina Puzriakova reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v5.2 CTNND1 Arina Puzriakova reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v5.2 CFAP20 Arina Puzriakova reviewed gene: CFAP20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Achchuthan Shanmugasundram Tag for-review was removed from gene: SCN8A.
Tag to_be_confirmed_NHSE was removed from gene: SCN8A.
Early onset or syndromic epilepsy v5.6 CACNB4 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: CACNB4.
Tag Q4_23_expert_review was removed from gene: CACNB4.
Early onset or syndromic epilepsy v5.6 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Early onset or syndromic epilepsy v5.6 TRIT1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TRIT1.
Early onset or syndromic epilepsy v5.6 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Early onset or syndromic epilepsy v5.6 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Early onset or syndromic epilepsy v5.6 PLA2G6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PLA2G6.
Early onset or syndromic epilepsy v5.6 PIGM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PIGM.
Early onset or syndromic epilepsy v5.6 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Early onset or syndromic epilepsy v5.6 HECTD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HECTD4.
Early onset or syndromic epilepsy v5.6 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Early onset or syndromic epilepsy v5.6 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova Tag Q4_23_MOI was removed from gene: EPHA2.
Early onset or syndromic epilepsy v5.6 AGO1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: AGO1.
Bilateral congenital or childhood onset cataracts v4.14 LETM1 Arina Puzriakova reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.14 EPHA2 Arina Puzriakova reviewed gene: EPHA2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts v4.13 LETM1 Arina Puzriakova Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bilateral congenital or childhood onset cataracts v4.13 EPHA2 Arina Puzriakova Source NHS GMS was added to EPHA2.
Mode of inheritance for gene EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Early onset or syndromic epilepsy v5.6 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Early onset or syndromic epilepsy v5.6 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Early onset or syndromic epilepsy v5.6 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
White matter disorders and cerebral calcification - narrow panel v4.2 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v4.2 ESAM Arina Puzriakova Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.6 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Early onset or syndromic epilepsy v5.6 KDM6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KDM6B.
Early onset or syndromic epilepsy v5.6 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.9 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Early onset or syndromic epilepsy v5.6 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Early onset or syndromic epilepsy v5.6 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Early onset or syndromic epilepsy v5.6 DNAJC6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC6.
Severe microcephaly v5.7 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from MCPH; primary microcephaly; autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Intellectual disability v6.8 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Intellectual disability v6.8 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.6 DPP6 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DPP6.
Severe microcephaly v5.6 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Severe microcephaly v5.6 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Severe microcephaly v5.5 TTI1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: TTI1.
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PPFIBP1.
Early onset or syndromic epilepsy v5.6 CRELD1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CRELD1.
Severe microcephaly v5.5 NSD2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: NSD2.
Severe microcephaly v5.5 MECP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MECP2.
Severe microcephaly v5.5 KMT2B Arina Puzriakova Tag Q4_23_promote_green was removed from gene: KMT2B.
Severe microcephaly v5.5 BUB1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BUB1.
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 ARF3 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ARF3.
Early onset or syndromic epilepsy v5.6 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Early onset or syndromic epilepsy v5.6 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Severe microcephaly v5.5 TTI1 Arina Puzriakova Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 PPFIBP1 Arina Puzriakova Source Expert Review Green was added to PPFIBP1.
Source NHS GMS was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 NSD2 Arina Puzriakova Source Expert Review Green was added to NSD2.
Source NHS GMS was added to NSD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 MECP2 Arina Puzriakova Source Expert Review Green was added to MECP2.
Source NHS GMS was added to MECP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 KMT2B Arina Puzriakova Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 DPP6 Arina Puzriakova Source Expert Review Amber was added to DPP6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Severe microcephaly v5.5 BUB1 Arina Puzriakova Source Expert Review Green was added to BUB1.
Source NHS GMS was added to BUB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ATP6V0C Arina Puzriakova Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.5 ARF3 Arina Puzriakova Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v5.4 DPP6 Arina Puzriakova reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v5.4 TTI1 Arina Puzriakova reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 NSD2 Arina Puzriakova reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 MECP2 Arina Puzriakova reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Severe microcephaly v5.4 KMT2B Arina Puzriakova commented on gene: KMT2B: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Severe microcephaly v5.4 BUB1 Arina Puzriakova edited their review of gene: BUB1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v5.4 ATP6V0C Arina Puzriakova reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v5.4 ARF3 Arina Puzriakova reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 SLC5A6 Eleanor Williams reviewed gene: SLC5A6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ZBTB47 Eleanor Williams reviewed gene: ZBTB47: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 U2AF2 Eleanor Williams reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 TRIT1 Eleanor Williams edited their review of gene: TRIT1: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v5.6 TMEM63B Eleanor Williams reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 SHQ1 Eleanor Williams reviewed gene: SHQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 SCN8A Eleanor Williams reviewed gene: SCN8A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 RAB5C Eleanor Williams reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PTCD3 Eleanor Williams reviewed gene: PTCD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PPP1R3F Eleanor Williams reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v5.6 PLA2G6 Eleanor Williams reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PIP5K1C Eleanor Williams reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 PIGM Eleanor Williams reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 PABPC1 Eleanor Williams reviewed gene: PABPC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 MAST4 Eleanor Williams reviewed gene: MAST4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 LETM1 Eleanor Williams reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 KDM6B Eleanor Williams reviewed gene: KDM6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 KCNH5 Eleanor Williams reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 HECTD4 Eleanor Williams reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ESAM Eleanor Williams reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 EIF4A2 Eleanor Williams reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 DNAJC6 Eleanor Williams reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CRELD1 Eleanor Williams reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 CNOT9 Eleanor Williams reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 CACNB4 Eleanor Williams reviewed gene: CACNB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v5.6 ATP6V0C Eleanor Williams reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v5.6 ASL Eleanor Williams edited their review of gene: ASL: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.6 ARF3 Eleanor Williams reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.6 AGO1 Eleanor Williams reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v5.5 ZBTB47 Achchuthan Shanmugasundram Source NHS GMS was added to ZBTB47.
Source Expert Review Green was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 U2AF2 Achchuthan Shanmugasundram Source NHS GMS was added to U2AF2.
Source Expert Review Green was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TRIT1 Achchuthan Shanmugasundram Source NHS GMS was added to TRIT1.
Source Expert Review Green was added to TRIT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 TMEM63B Achchuthan Shanmugasundram Source NHS GMS was added to TMEM63B.
Source Expert Review Green was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SLC5A6 Achchuthan Shanmugasundram Source NHS GMS was added to SLC5A6.
Early onset or syndromic epilepsy v5.5 SHQ1 Achchuthan Shanmugasundram Source NHS GMS was added to SHQ1.
Source Expert Review Green was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 SCN8A Achchuthan Shanmugasundram Mode of inheritance for gene SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v5.5 RAB5C Achchuthan Shanmugasundram Source NHS GMS was added to RAB5C.
Source Expert Review Green was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PTCD3 Achchuthan Shanmugasundram Source NHS GMS was added to PTCD3.
Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PPP1R3F Achchuthan Shanmugasundram Source NHS GMS was added to PPP1R3F.
Source Expert Review Green was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIP5K1C Achchuthan Shanmugasundram Source NHS GMS was added to PIP5K1C.
Source Expert Review Green was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PIGM Achchuthan Shanmugasundram Source Expert Review Green was added to PIGM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 PABPC1 Achchuthan Shanmugasundram Source NHS GMS was added to PABPC1.
Source Expert Review Green was added to PABPC1.
Mode of inheritance for gene PABPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 MAST4 Achchuthan Shanmugasundram Source NHS GMS was added to MAST4.
Source Expert Review Green was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KDM6B Achchuthan Shanmugasundram Source Expert Review Green was added to KDM6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 HECTD4 Achchuthan Shanmugasundram Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ESAM Achchuthan Shanmugasundram Source NHS GMS was added to ESAM.
Source Expert Review Green was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 EIF4A2 Achchuthan Shanmugasundram Source NHS GMS was added to EIF4A2.
Source Expert Review Green was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 DNAJC6 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CRELD1 Achchuthan Shanmugasundram Source NHS GMS was added to CRELD1.
Source Expert Review Green was added to CRELD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CNOT9 Achchuthan Shanmugasundram Source NHS GMS was added to CNOT9.
Source Expert Review Green was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 CACNB4 Achchuthan Shanmugasundram Source Expert Review Red was added to CACNB4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset or syndromic epilepsy v5.5 ATP6V0C Achchuthan Shanmugasundram Source NHS GMS was added to ATP6V0C.
Source Expert Review Green was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ASL Achchuthan Shanmugasundram Source NHS GMS was added to ASL.
Source Expert Review Green was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 ARF3 Achchuthan Shanmugasundram Source NHS GMS was added to ARF3.
Source Expert Review Green was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v5.5 AGO1 Achchuthan Shanmugasundram Source NHS GMS was added to AGO1.
Source Expert Review Green was added to AGO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Distal myopathies v4.3 SMPX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMPX.
Tag Q3_23_MOI was removed from gene: SMPX.
Distal myopathies v4.3 SMPX Eleanor Williams reviewed gene: SMPX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Distal myopathies v4.2 SMPX Achchuthan Shanmugasundram Source Expert Review Green was added to SMPX.
Source NHS GMS was added to SMPX.
Mode of inheritance for gene SMPX 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)
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: UCHL1.
Tag Q3_23_MOI was removed from gene: UCHL1.
Hereditary ataxia with onset in adulthood v5.3 TDP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TDP1.
Hereditary ataxia with onset in adulthood v5.3 UCHL1 Eleanor Williams reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.3 TDP1 Eleanor Williams reviewed gene: TDP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v5.2 UCHL1 Achchuthan Shanmugasundram Source Expert Review Green was added to UCHL1.
Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v5.2 TDP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.3 ZC4H2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ZC4H2.
Clefting v5.3 TRRAP Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TRRAP.
Clefting v5.3 STAG2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: STAG2.
Clefting v5.3 SMARCA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SMARCA4.
Clefting v5.3 PGM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGM1.
Clefting v5.3 PGAP3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PGAP3.
Clefting v5.3 KAT6B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KAT6B.
Clefting v5.3 HNRNPK Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: HNRNPK.
Clefting v5.3 GLI2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GLI2.
Clefting v5.3 CNTNAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNTNAP1.
Clefting v5.3 AMOTL1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMOTL1.
Clefting v5.3 ALX1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALX1.
Clefting v5.3 ZC4H2 Sarah Leigh reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v5.3 TRRAP Sarah Leigh reviewed gene: TRRAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 STAG2 Sarah Leigh reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v5.3 SMARCA4 Sarah Leigh reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 PGM1 Sarah Leigh reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 PGAP3 Sarah Leigh reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 KAT6B Sarah Leigh reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v5.3 HNRNPK Sarah Leigh reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 GLI2 Sarah Leigh reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 CNTNAP1 Sarah Leigh reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.3 AMOTL1 Sarah Leigh reviewed gene: AMOTL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v5.3 ALX1 Sarah Leigh edited their review of gene: ALX1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v5.2 ZC4H2 Achchuthan Shanmugasundram Source Expert Review Green was added to ZC4H2.
Source NHS GMS was added to ZC4H2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 TRRAP Achchuthan Shanmugasundram Source Expert Review Green was added to TRRAP.
Source NHS GMS was added to TRRAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 STAG2 Achchuthan Shanmugasundram Source Expert Review Green was added to STAG2.
Source NHS GMS was added to STAG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 SMARCA4 Achchuthan Shanmugasundram Source Expert Review Green was added to SMARCA4.
Source NHS GMS was added to SMARCA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGM1 Achchuthan Shanmugasundram Source Expert Review Green was added to PGM1.
Source NHS GMS was added to PGM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 PGAP3 Achchuthan Shanmugasundram Source Expert Review Green was added to PGAP3.
Source NHS GMS was added to PGAP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 KAT6B Achchuthan Shanmugasundram Source Expert Review Green was added to KAT6B.
Source NHS GMS was added to KAT6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 HNRNPK Achchuthan Shanmugasundram Source Expert Review Green was added to HNRNPK.
Source NHS GMS was added to HNRNPK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 GLI2 Achchuthan Shanmugasundram Source Expert Review Green was added to GLI2.
Source NHS GMS was added to GLI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 CNTNAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to CNTNAP1.
Source NHS GMS was added to CNTNAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 AMOTL1 Achchuthan Shanmugasundram Source Expert Review Green was added to AMOTL1.
Source NHS GMS was added to AMOTL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v5.2 ALX1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALX1.
Source NHS GMS was added to ALX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Achchuthan Shanmugasundram Tag watchlist was removed from gene: THG1L.
Tag Q4_23_promote_green was removed from gene: THG1L.
Tag Q4_23_NHS_review was removed from gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DLG4.
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL.
Tag Q4_23_NHS_review was removed from gene: ASL.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC3.
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Ataxia and cerebellar anomalies - narrow panel v5.3 UCHL1 Sarah Leigh commented on gene: UCHL1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v5.3 THG1L Sarah Leigh reviewed gene: THG1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 LETM1 Sarah Leigh commented on gene: LETM1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v5.3 DNAJC3 Sarah Leigh reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 DLG4 Sarah Leigh reviewed gene: DLG4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v5.3 ASL Sarah Leigh reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.3 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 UCHL1 Achchuthan Shanmugasundram Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v5.2 THG1L Achchuthan Shanmugasundram Source Expert Review Green was added to THG1L.
Source NHS GMS was added to THG1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DNAJC3 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC3.
Source NHS GMS was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DLG4 Achchuthan Shanmugasundram Source Expert Review Green was added to DLG4.
Source NHS GMS was added to DLG4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 ASL Achchuthan Shanmugasundram Source Expert Review Green was added to ASL.
Source NHS GMS was added to ASL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v5.2 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.4 TAMM41 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: TAMM41.
Rhabdomyolysis and metabolic muscle disorders v4.4 PNPLA2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: PNPLA2.
Rhabdomyolysis and metabolic muscle disorders v4.4 ISCU Arina Puzriakova Phenotypes for gene: ISCU were changed from Myopathy with lactic acidosis, hereditary 255125 to Myopathy with lactic acidosis, hereditary, OMIM:255125
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova Tag for-review was removed from gene: ISCU.
Tag to_be_confirmed_NHSE was removed from gene: ISCU.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ABHD5.
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova edited their review of gene: ABHD5: Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova changed review comment from: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.4 ANO10 Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: ANO10.
Tag Q2_24_demote_amber tag was added to gene: ANO10.
Tag Q2_24_expert_review tag was added to gene: ANO10.
Mitochondrial disorders v6.4 BTD Achchuthan Shanmugasundram Tag Q3_23_expert_review was removed from gene: BTD.
Tag Q2_24_demote_amber tag was added to gene: BTD.
Tag Q2_24_expert_review tag was added to gene: BTD.
Rhabdomyolysis and metabolic muscle disorders v4.3 ISCU Arina Puzriakova edited their review of gene: ISCU: Added comment: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 TAMM41 Arina Puzriakova reviewed gene: TAMM41: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 PNPLA2 Arina Puzriakova reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.3 ABHD5 Arina Puzriakova reviewed gene: ABHD5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 TAMM41 Arina Puzriakova Source Expert Review Green was added to TAMM41.
Source NHS GMS was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 PNPLA2 Arina Puzriakova Source Expert Review Green was added to PNPLA2.
Source NHS GMS was added to PNPLA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v4.2 ISCU Arina Puzriakova Source NHS GMS was added to ISCU.
Mode of inheritance for gene ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v4.2 ABHD5 Arina Puzriakova Source Expert Review Green was added to ABHD5.
Source NHS GMS was added to ABHD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.4 HECTD4 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: HECTD4.
Malformations of cortical development v5.4 COL4A2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A2.
Tag Q4_23_NHS_review was removed from gene: COL4A2.
Intellectual disability v6.7 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
DDG2P v4.3 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.4 COL4A1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: COL4A1.
Tag Q4_23_NHS_review was removed from gene: COL4A1.
Malformations of cortical development v5.4 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; hereditary cerebral malformation, MONDO:0957008 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CASP2.
Malformations of cortical development v5.3 HECTD4 Arina Puzriakova Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A2 Arina Puzriakova Source NHS GMS was added to COL4A2.
Source Expert Review Green was added to COL4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 COL4A1 Arina Puzriakova Source NHS GMS was added to COL4A1.
Source Expert Review Green was added to COL4A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.3 CASP2 Arina Puzriakova Source NHS GMS was added to CASP2.
Source Expert Review Green was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v5.2 HECTD4 Arina Puzriakova commented on gene: HECTD4: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Malformations of cortical development v5.2 COL4A2 Arina Puzriakova reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 COL4A1 Arina Puzriakova reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v5.2 CASP2 Arina Puzriakova reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.4 HPDL Achchuthan Shanmugasundram Tag for-review was removed from gene: HPDL.
Tag to_be_confirmed_NHSE was removed from gene: HPDL.
Mitochondrial disorders v6.4 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Mitochondrial disorders v6.4 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Tag Q4_23_NHS_review was removed from gene: TEFM.
Mitochondrial disorders v6.4 TAMM41 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TAMM41.
Tag Q4_23_NHS_review was removed from gene: TAMM41.
Mitochondrial disorders v6.4 SLC52A3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A3.
Tag Q4_23_MOI was removed from gene: SLC52A3.
Mitochondrial disorders v6.4 SLC52A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC52A2.
Mitochondrial disorders v6.4 SLC25A36 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SLC25A36.
Tag Q4_23_NHS_review was removed from gene: SLC25A36.
Mitochondrial disorders v6.4 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Mitochondrial disorders v6.4 HADHB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HADHB.
Mitochondrial disorders v6.4 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Mitochondrial disorders v6.4 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Mitochondrial disorders v6.4 ATP5E Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP5E.
Mitochondrial disorders v6.4 SLC25A24 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A24.
Mitochondrial disorders v6.4 SLC25A20 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC25A20.
Mitochondrial disorders v6.4 SLC22A5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC22A5.
Mitochondrial disorders v6.4 QARS Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: QARS.
Mitochondrial disorders v6.4 PPOX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPOX.
Mitochondrial disorders v6.4 PLA2G6 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PLA2G6.
Mitochondrial disorders v6.4 PITRM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PITRM1.
Mitochondrial disorders v6.4 PANK2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PANK2.
Mitochondrial disorders v6.4 OXCT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: OXCT1.
Hydrocephalus v4.6 HYLS1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: HYLS1.
Hydrocephalus v4.6 MYMK Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: MYMK.
Hydrocephalus v4.6 ERF Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: ERF.
Hydrocephalus v4.6 MYMK Arina Puzriakova reviewed gene: MYMK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 HYLS1 Arina Puzriakova reviewed gene: HYLS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.6 ERF Arina Puzriakova reviewed gene: ERF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.5 MYMK Arina Puzriakova Source Expert Review Amber was added to MYMK.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Hydrocephalus v4.5 ERF Arina Puzriakova Source Expert Review Red was added to ERF.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Mitochondrial disorders v6.4 TEFM Sarah Leigh edited their review of gene: TEFM: Changed rating: GREEN
Mitochondrial disorders v6.4 TAMM41 Sarah Leigh edited their review of gene: TAMM41: Changed rating: GREEN
Mitochondrial disorders v6.4 SLC25A36 Sarah Leigh edited their review of gene: SLC25A36: Changed rating: GREEN
Mitochondrial disorders v6.4 QARS Sarah Leigh edited their review of gene: QARS: Changed rating: GREEN
Mitochondrial disorders v6.4 PPOX Sarah Leigh edited their review of gene: PPOX: Changed rating: GREEN
Mitochondrial disorders v6.4 PANK2 Sarah Leigh edited their review of gene: PANK2: Changed rating: GREEN
Mitochondrial disorders v6.4 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Changed rating: GREEN
Mitochondrial disorders v6.4 HADHB Sarah Leigh edited their review of gene: HADHB: Changed rating: GREEN
Holoprosencephaly v4.9 DISP1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: DISP1.
Holoprosencephaly v4.9 DISP1 Arina Puzriakova changed review comment from: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval.; to: The rating of this gene has been demoted to Amber following NHS Genomic Medicine Service approval.
Holoprosencephaly v4.9 DISP1 Arina Puzriakova reviewed gene: DISP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Holoprosencephaly v4.8 DISP1 Arina Puzriakova Source Expert Review Amber was added to DISP1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Mitochondrial disorders v6.3 TEFM Sarah Leigh reviewed gene: TEFM: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 TAMM41 Sarah Leigh reviewed gene: TAMM41: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC52A3 Sarah Leigh commented on gene: SLC52A3: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC52A2 Sarah Leigh edited their review of gene: SLC52A2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A36 Sarah Leigh reviewed gene: SLC25A36: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC25A24 Sarah Leigh commented on gene: SLC25A24: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 SLC25A20 Sarah Leigh edited their review of gene: SLC25A20: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 SLC22A5 Sarah Leigh commented on gene: SLC22A5: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 QARS Sarah Leigh reviewed gene: QARS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PPOX Sarah Leigh edited their review of gene: PPOX: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PLA2G6 Sarah Leigh commented on gene: PLA2G6: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v6.3 PITRM1 Sarah Leigh edited their review of gene: PITRM1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 PANK2 Sarah Leigh reviewed gene: PANK2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 OXCT1 Sarah Leigh edited their review of gene: OXCT1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HPDL Sarah Leigh edited their review of gene: HPDL: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 HADHB Sarah Leigh edited their review of gene: HADHB: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 COX11 Sarah Leigh edited their review of gene: COX11: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.3 ATP5E Sarah Leigh edited their review of gene: ATP5E: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v6.2 TEFM Achchuthan Shanmugasundram Source NHS GMS was added to TEFM.
Source Expert Review Green was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 TAMM41 Achchuthan Shanmugasundram Source NHS GMS was added to TAMM41.
Source Expert Review Green was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC52A3 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A3.
Mode of inheritance for gene SLC52A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC52A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A36 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A36.
Source Expert Review Green was added to SLC25A36.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A24 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A24.
Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC25A20 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 SLC22A5 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC22A5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 QARS Achchuthan Shanmugasundram Source NHS GMS was added to QARS.
Source Expert Review Green was added to QARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PPOX Achchuthan Shanmugasundram Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PLA2G6 Achchuthan Shanmugasundram Source NHS GMS was added to PLA2G6.
Source Expert Review Green was added to PLA2G6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PITRM1 Achchuthan Shanmugasundram Source NHS GMS was added to PITRM1.
Source Expert Review Green was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 PANK2 Achchuthan Shanmugasundram Source NHS GMS was added to PANK2.
Source Expert Review Green was added to PANK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 OXCT1 Achchuthan Shanmugasundram Source Expert Review Green was added to OXCT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HPDL Achchuthan Shanmugasundram Source NHS GMS was added to HPDL.
Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 HADHB Achchuthan Shanmugasundram Source Expert Review Green was added to HADHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX5A Achchuthan Shanmugasundram Source NHS GMS was added to COX5A.
Source Expert Review Green was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v6.2 ATP5E Achchuthan Shanmugasundram Source NHS GMS was added to ATP5E.
Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.6 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Early onset or syndromic epilepsy v5.4 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Monogenic hearing loss v4.41 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
DDG2P v4.2 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, NEUROPATHY, AND DEAFNESS, OMIM:617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy v1.478 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.8 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Hereditary neuropathy or pain disorder v4.7 SPTBN4 Arina Puzriakova Tag for-review was removed from gene: SPTBN4.
Tag to_be_confirmed_NHSE was removed from gene: SPTBN4.
Hereditary neuropathy or pain disorder v4.7 NEMF Arina Puzriakova Phenotypes for gene: NEMF were changed from Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, OMIM:619099
Hereditary neuropathy or pain disorder v4.6 NEMF Arina Puzriakova Tag watchlist was removed from gene: NEMF.
Tag for-review was removed from gene: NEMF.
Tag to_be_confirmed_NHSE was removed from gene: NEMF.
Hereditary neuropathy or pain disorder v4.6 SYT2 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SYT2.
Hereditary neuropathy or pain disorder v4.6 SPTAN1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: SPTAN1.
Hereditary neuropathy or pain disorder v4.6 SARS Arina Puzriakova Tag Q4_23_promote_green was removed from gene: SARS.
Tag Q4_23_NHS_review was removed from gene: SARS.
Hereditary neuropathy or pain disorder v4.6 PPOX Arina Puzriakova Phenotypes for gene: PPOX were changed from Porphyria variegata, 176200; Skin photosensitivity. Acute episodes similar to AIP to Porphyria variegata, OMIM:176200; Sensory neuropathy, HP:0000763
Hereditary neuropathy or pain disorder v4.5 PPOX Arina Puzriakova Tag Q3_23_MOI was removed from gene: PPOX.
Hereditary neuropathy or pain disorder v4.5 ITPR3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: ITPR3.
Hereditary neuropathy or pain disorder v4.5 DNAJC3 Arina Puzriakova Phenotypes for gene: DNAJC3 were changed from Cerebellar ataxia, neuropathy with SNCV, hearing loss, diabetes mellitus; Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Hereditary neuropathy or pain disorder v4.4 DNAJC3 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DNAJC3.
Hereditary neuropathy or pain disorder v4.4 DHX9 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHX9.
Hereditary neuropathy or pain disorder v4.4 DHTKD1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: DHTKD1.
Hereditary neuropathy or pain disorder v4.4 AGTPBP1 Arina Puzriakova Phenotypes for gene: AGTPBP1 were changed from Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 to Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Hereditary neuropathy or pain disorder v4.3 SPTBN4 Arina Puzriakova edited their review of gene: SPTBN4: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v4.3 NEMF Arina Puzriakova edited their review of gene: NEMF: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SYT2 Arina Puzriakova reviewed gene: SYT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SPTAN1 Arina Puzriakova reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 SLC12A6 Arina Puzriakova edited their review of gene: SLC12A6: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 PPOX Arina Puzriakova reviewed gene: PPOX: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 ITPR3 Arina Puzriakova reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DNAJC3 Arina Puzriakova reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.3 DHX9 Arina Puzriakova edited their review of gene: DHX9: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 DHTKD1 Arina Puzriakova reviewed gene: DHTKD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v4.3 AGTPBP1 Arina Puzriakova reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 SYT2 Arina Puzriakova Source Expert Review Green was added to SYT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTBN4 Arina Puzriakova Source NHS GMS was added to SPTBN4.
Source Expert Review Green was added to SPTBN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SPTAN1 Arina Puzriakova Source NHS GMS was added to SPTAN1.
Source Expert Review Green was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SLC12A6 Arina Puzriakova Source Expert Review Green was added to SLC12A6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 PPOX Arina Puzriakova Mode of inheritance for gene PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v4.2 NEMF Arina Puzriakova Source NHS GMS was added to NEMF.
Source Expert Review Green was added to NEMF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 ITPR3 Arina Puzriakova Source NHS GMS was added to ITPR3.
Source Expert Review Green was added to ITPR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DNAJC3 Arina Puzriakova Source Expert Review Green was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHX9 Arina Puzriakova Source NHS GMS was added to DHX9.
Source Expert Review Green was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 DHTKD1 Arina Puzriakova Source Expert Review Green was added to DHTKD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v4.2 AGTPBP1 Arina Puzriakova Source Expert Review Green was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova edited their review of Region: ISCA-37467-Gain: Added comment: The rating of this region has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova reviewed Region: ISCA-46292-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova changed review comment from: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.; to: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: two cases (PMID: 30158690; 33758131) with intragenic STAG2 deletions but listed as sufficient evidence in ClinGen. Region encompasses STAG2 and some of XIAP. Phenotype: holoprosencephaly and/or developmental delay/ID based on LOF of STAG2 gene. Affected females are reported.
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova changed review comment from: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism). Modulated phenotype in females is reported.; to: The rating of this region has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.
Intellectual disability v6.5 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Holoprosencephaly v4.7 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova Publications for Region: ISCA-46292-Loss were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Tag Q3_23_promote_green was removed from Region: ISCA-37467-Gain.
Intellectual disability v6.4 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Severe microcephaly v5.3 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Holoprosencephaly v4.7 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Early onset or syndromic epilepsy v5.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Intellectual disability v6.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Limb disorders v5.2 ISCA-37467-Gain Arina Puzriakova Haploinsufficiency Score for ISCA-37467-Gain was changed from None to .
Source Expert Review Green was added to Region: ISCA-37467-Gain.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.2 ISCA-46292-Loss Arina Puzriakova Region: ISCA-46292-Loss was added
Region: ISCA-46292-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46292-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Severe microcephaly v5.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Severe microcephaly. Sources: ClinGen,Expert Review Amber
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Holoprosencephaly v4.6 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Holoprosencephaly - NOT chromosomal. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v5.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Early onset or syndromic epilepsy. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Gain was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Gain was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rare multisystem ciliopathy Super panel v15.3 Arina Puzriakova Panel version 15.2 has been signed off on 2024-05-01
Hypotonic infant v29.2 Arina Puzriakova Panel version 29.1 has been signed off on 2024-05-01
Cystic renal disease v8.4 Eleanor Williams Panel version 8.3 has been signed off on 2024-05-01
Hereditary ataxia and cerebellar anomalies - childhood onset v15.3 Eleanor Williams Panel version 15.2 has been signed off on 2024-05-01
Sudden unexplained death or survivors of a cardiac event v19.74 Arina Puzriakova Panel version 19.73 has been signed off on 2024-05-01
Childhood onset leukodystrophy v19.3 Eleanor Williams Panel version 19.2 has been signed off on 2024-05-01
Unexplained death in infancy and sudden unexplained death in childhood v9.8 Arina Puzriakova Panel version 9.7 has been signed off on 2024-05-01
Cerebral malformation v11.3 Eleanor Williams Panel version 11.2 has been signed off on 2024-05-01
Other rare neuromuscular disorders v21.3 Eleanor Williams Panel version 21.2 has been signed off on 2024-05-01
Paediatric disorders v45.3 Arina Puzriakova Panel version 45.2 has been signed off on 2024-05-01
Short QT syndrome v3.12 Achchuthan Shanmugasundram Panel version 3.11 has been signed off on 2024-05-01
Progressive cardiac conduction disease v2.8 Achchuthan Shanmugasundram Panel version 2.7 has been signed off on 2024-05-01
Catecholaminergic polymorphic VT v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Hypertrophic cardiomyopathy v4.9 Achchuthan Shanmugasundram Panel version 4.8 has been signed off on 2024-05-01
Autoinflammatory disorders v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2024-05-01
Autoinflammatory disorders v2.0 Eleanor Williams promoted panel to version 2.0
Brugada syndrome and cardiac sodium channel disease v3.10 Achchuthan Shanmugasundram Panel version 3.9 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Differences in sex development v4.6 Achchuthan Shanmugasundram Panel version 4.5 has been signed off on 2024-05-01
Unexplained young onset end-stage renal disease v4.0 Eleanor Williams promoted panel to version 4.0
Arrhythmogenic right ventricular cardiomyopathy v3.11 Achchuthan Shanmugasundram Panel version 3.10 has been signed off on 2024-05-01
Cystic kidney disease v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Cystic kidney disease v5.0 Eleanor Williams promoted panel to version 5.0
Arthrogryposis v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Arthrogryposis v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Retinal disorders v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Retinal disorders v5.0 Eleanor Williams promoted panel to version 5.0
Distal myopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Distal myopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Severe microcephaly v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Malformations of cortical development v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Rhabdomyolysis and metabolic muscle disorders v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Severe microcephaly v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Rhabdomyolysis and metabolic muscle disorders v4.0 Arina Puzriakova promoted panel to version 4.0
Neurological ciliopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Rare syndromic craniosynostosis or isolated multisuture synostosis v5.0 Arina Puzriakova promoted panel to version 5.0
Ophthalmological ciliopathies v4.0 Eleanor Williams promoted panel to version 4.0
Skeletal ciliopathies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Neurological ciliopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Neurological segmental overgrowth v2.13 Ivone Leong Panel version 2.12 has been signed off on 2024-05-01
Congenital myaesthenic syndrome v4.6 Ivone Leong Panel version 4.5 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Ataxia and cerebellar anomalies - narrow panel v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Skeletal ciliopathies v4.0 Arina Puzriakova promoted panel to version 4.0
Limb disorders v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
White matter disorders and cerebral calcification - narrow panel v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Congenital myopathy v4.38 Ivone Leong Panel version 4.37 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.0 Eleanor Williams promoted panel to version 4.0
White matter disorders and cerebral calcification - narrow panel v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Congenital muscular dystrophy v4.24 Ivone Leong Panel version 4.23 has been signed off on 2024-05-01
DDG2P v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Hereditary neuropathy or pain disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Limb disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Hereditary neuropathy or pain disorder v4.0 Eleanor Williams promoted panel to version 4.0
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.33 Ivone Leong Panel version 4.32 has been signed off on 2024-05-01
DDG2P v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Paediatric motor neuronopathies v3.7 Ivone Leong Panel version 3.6 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Adult onset leukodystrophy v4.0 Eleanor Williams promoted panel to version 4.0
Mitochondrial disorders v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2024-05-01
Familial hypoparathyroidism v2.15 Ivone Leong Panel version 2.14 has been signed off on 2024-05-01
Paediatric disorders - additional genes v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Skeletal dysplasia v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Skeletal dysplasia v5.0 Arina Puzriakova promoted panel to version 5.0
Possible mitochondrial disorder - nuclear genes v3.106 Ivone Leong Panel version 3.105 has been signed off on 2024-05-01
Clefting v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Paediatric or syndromic cardiomyopathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2024-05-01
Childhood onset hereditary spastic paraplegia v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Mitochondrial disorder with complex IV deficiency v3.21 Ivone Leong Panel version 3.20 has been signed off on 2024-05-01
Clefting v5.0 Arina Puzriakova promoted panel to version 5.0
Childhood onset hereditary spastic paraplegia v5.0 Eleanor Williams promoted panel to version 5.0
Respiratory ciliopathies including non-CF bronchiectasis v3.11 Ivone Leong Panel version 3.10 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Adult onset hereditary spastic paraplegia v4.0 Eleanor Williams promoted panel to version 4.0
Laterality disorders and isomerism v3.10 Ivone Leong Panel version 3.9 has been signed off on 2024-05-01
Mitochondrial disorders v6.0 Arina Puzriakova promoted panel to version 6.0
Paediatric or syndromic cardiomyopathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Mitochondrial disorders v5.0 Arina Puzriakova promoted panel to version 5.0
Renal ciliopathies v3.6 Ivone Leong Panel version 3.5 has been signed off on 2024-05-01
Fetal anomalies v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2024-05-01
Early onset or syndromic epilepsy v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-05-01
Fetal anomalies v4.0 Arina Puzriakova promoted panel to version 4.0
Holoprosencephaly v4.5 Ivone Leong Panel version 4.4 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Adult onset neurodegenerative disorder v5.0 Eleanor Williams promoted panel to version 5.0
Early onset or syndromic epilepsy v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Long QT syndrome v3.8 Ivone Leong Panel version 3.7 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.1 Eleanor Williams Panel version 5.0 has been signed off on 2024-05-01
Likely inborn error of metabolism v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Primary immunodeficiency or monogenic inflammatory bowel disease v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Dilated and arrhythmogenic cardiomyopathy v2.25 Ivone Leong Panel version 2.23 has been signed off on 2024-05-01
Hereditary ataxia with onset in adulthood v5.0 Eleanor Williams promoted panel to version 5.0
Primary immunodeficiency or monogenic inflammatory bowel disease v5.0 Arina Puzriakova promoted panel to version 5.0
Intellectual disability v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Monogenic hearing loss v4.40 Ivone Leong Panel version 4.39 has been signed off on 2024-05-01
Likely inborn error of metabolism v5.0 Arina Puzriakova promoted panel to version 5.0
Confirmed Fanconi anaemia or Bloom syndrome v2.6 Ivone Leong Panel version 2.5 has been signed off on 2024-05-01
Congenital disorders of glycosylation v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-05-01
Intellectual disability v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Congenital disorders of glycosylation v5.0 Arina Puzriakova promoted panel to version 5.0
Dilated and arrhythmogenic cardiomyopathy v2.24 Ivone Leong Panel version 2.23 has been signed off on 2024-02-01
Paediatric disorders v35.1834 Achchuthan Shanmugasundram Changed child panels to: Intellectual disability; Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Clefting; Skeletal dysplasia; Monogenic hearing loss; Limb disorders; DDG2P; Skeletal ciliopathies; Neurological ciliopathies; Paediatric disorders - additional genes; Ophthalmological ciliopathies; Renal ciliopathies
Unexplained death in infancy and sudden unexplained death in childhood v6.430 Eleanor Williams Changed child panels to: Early onset or syndromic epilepsy; Likely inborn error of metabolism - targeted testing not possible; Hypertrophic cardiomyopathy; Catecholaminergic polymorphic VT; Paediatric or syndromic cardiomyopathy; Short QT syndrome; Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome and cardiac sodium channel disease; Long QT syndrome; Dilated and arrhythmogenic cardiomyopathy; Progressive cardiac conduction disease
Confirmed Fanconi anaemia or Bloom syndrome v2.5 Ivone Leong List of related panels changed from R229; R258 to R229; R258; Confirmed Fanconi anaemia or Bloom syndrome - mutation testing; Cytopenia - Fanconi breakage testing indicated
Differences in sex development v4.5 Ivone Leong Panel name changed from Disorders of sex development to Differences in sex development
List of related panels changed from R146 to R146; Disorders of sex development
Intellectual disability v5.558 Arina Puzriakova Panel name changed from Intellectual disability - microarray and sequencing to Intellectual disability
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability - microarray and sequencing; R29
Intellectual disability v5.557 DIP2B Dmitrijs Rots reviewed gene: DIP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.557 ADGRL1 Dmitrijs Rots gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to PubMed: 35907405
Phenotypes for gene: ADGRL1 were set to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders
Review for gene: ADGRL1 was set to GREEN
Added comment: More than 10 cases described in PubMed: 35907405
Sources: Literature
Hypertrophic cardiomyopathy v4.7 SVIL Dmitrijs Rots gene: SVIL was added
gene: SVIL was added to Hypertrophic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: SVIL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SVIL were set to PMID: 36778260
Phenotypes for gene: SVIL were set to HCM
Review for gene: SVIL was set to AMBER
Added comment: In the novel paper described:"the excess burden is even greater at 15.3-fold (95% CI: 5.7-41.3; P:7x10−7) when restricting the analysis to high confidence LoF variants affecting the predominant SVIL transcript in LV (ENST00000375400) (Supplementary Table 6b). In one family, the SVIL LoF variant (p.(Gln255*)) was carried by two cousins with HCM (parents deceased), providing some evidence of co-segregation. Taken together, these data support SVIL as a novel HCM disease gene."
Strong statistical evidence + one family segregating.
Sources: Literature
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots edited their review of gene: FLT4: Added comment: Statistically proven 30582441 enrichment in multiple affected cases. Enough for green rating.; Changed phenotypes to: Congenital heart defect; Set current diagnostic: yes
Familial non syndromic congenital heart disease v1.80 FLT4 Dmitrijs Rots reviewed gene: FLT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30582441; Phenotypes: Congenital; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thrombophilia with a likely monogenic cause v2.5 PLG Zornitza Stark reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 35244080, 27976734; Phenotypes: Dysplasminogenemia, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Familial breast cancer v1.20 BARD1 Dmitrijs Rots edited their review of gene: BARD1: Added comment: PMID: 37592023 metaanlysis also reports significant association with breast cancer; Changed publications to: PMID: 37592023
Familial breast cancer v1.20 BARD1 Dmitrijs Rots reviewed gene: BARD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v5.31 SLC35A3 Hannah Knight reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777481, 24031089, 28328131, 33416188; Phenotypes: Arthrogryposis, impaired intellectual development, and seizures, 615553 (3), Autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.557 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Early onset or syndromic epilepsy v4.196 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Severe microcephaly v4.88 YIF1B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: YIF1B.
Early onset or syndromic epilepsy v4.196 TRIT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TRIT1.
Ataxia and cerebellar anomalies - narrow panel v4.64 SVBP Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SVBP.
Intellectual disability v5.557 RNPC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RNPC3.
Mitochondrial disorders v4.169 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Likely inborn error of metabolism v4.137 PITRM1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PITRM1.
Intellectual disability v5.557 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Arthrogryposis v5.31 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Intellectual disability v5.557 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Early onset or syndromic epilepsy v4.196 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Hypertrophic cardiomyopathy v4.7 ALPK3 Dmitrijs Rots commented on gene: ALPK3: As described by Luis Lopes, should be BOTH monoallelic and biallelic on this panel.
Intellectual disability v5.557 CEP295 Achchuthan Shanmugasundram Phenotypes for gene: CEP295 were changed from Seckel syndrome 11, OMIM # 620767 to Seckel syndrome 11, OMIM:620767
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Classified gene: CEP295 as Amber List (moderate evidence)
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Gene: cep295 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.555 CEP295 Achchuthan Shanmugasundram reviewed gene: CEP295: Rating: AMBER; Mode of pathogenicity: None; Publications: 38154379; Phenotypes: Seckel syndrome 11, OMIM:620767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: DOCK4.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Classified gene: DOCK4 as Amber List (moderate evidence)
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:38526744 reported seven unrelated individuals with heterozygous variants and with developmental delay or intellectual disability, of which four had ID. Three of them with ID had heterozygous variants, while one had compound heterozygous variants. There is also some functional evidence available.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Gene: dock4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.553 DOCK4 Achchuthan Shanmugasundram reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38526744; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.553 GTF3C5 Achchuthan Shanmugasundram Publications for gene: GTF3C5 were set to 38520561; 35503477
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram edited their review of gene: GTF3C5: Changed publications to: 35503477, 38520561
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Classified gene: GTF3C5 as Amber List (moderate evidence)
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Gene: gtf3c5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.551 GTF3C5 Achchuthan Shanmugasundram Phenotypes for gene: GTF3C5 were changed from neurodevelopmental disorder MONDO:0700092, GTF3C5-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GTF3C5.
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram reviewed gene: GTF3C5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v3.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Childhood onset dystonia, chorea or related movement disorder v3.78 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Neurological ciliopathies v3.20 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Ophthalmological ciliopathies v3.7 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Intellectual disability v5.550 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Rare multisystem ciliopathy disorders v1.172 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
DDG2P v3.90 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome to Stromme syndrome, OMIM:243605
Fetal anomalies v3.169 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605 to Stromme syndrome, OMIM:243605
Unexplained young onset end-stage renal disease v3.42 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
CAKUT v1.177 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; bilateral renal hypoplasia; Duodenal atresia; Hydronephrosis to Stromme syndrome, OMIM:243605
Limb disorders v4.23 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Polydactyly; Stromme syndrome 243605 to Stromme syndrome, OMIM:243605
Severe microcephaly v4.88 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from MPD; microcephalic primordial dwarfism; Stromme syndrome, 243605; Microcephaly to Stromme syndrome, OMIM:243605; Microcephalic primordial dwarfism
Intellectual disability v5.549 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Clefting v4.111 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Severe microcephaly v4.87 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 6, 616835; MGORS6; primordial dwarfism to Meier-Gorlin syndrome 6, OMIM:616835; Microcephalic primordial dwarfism
Intellectual disability v5.548 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; INSULIN-LIKE GROWTH FACTOR I DEFICIENCY (IGF1 DEFICIENCY) to Insulin-like growth factor I deficiency, OMIM:608747
Monogenic hearing loss v4.39 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency,608747; GrowthretardationwithdeafnessandmentalretardationduetoIGF1deficiency,608747 to Insulin-like growth factor I deficiency, OMIM:608747
DDG2P v3.89 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Fetal anomalies v3.168 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY to Insulin-like growth factor I deficiency, OMIM:608747
IUGR and IGF abnormalities v1.69 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; Insulin-Like Growth Factor I Deficiency to Insulin-like growth factor I deficiency, OMIM:608747
Silver Russell syndrome v1.13 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency 608747 to Insulin-like growth factor I deficiency, OMIM:608747
Severe microcephaly v4.86 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; MPD; microcephalic primordial dwarfism to Insulin-like growth factor I deficiency, OMIM:608747; Microcephalic primordial dwarfism
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, OMIM:606593 to LIG4 syndrome, OMIM:606593
Haematological malignancies cancer susceptibility v4.5 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Ligase IV syndrome; Lymphoma; ALL
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, 606593{Multiple myeloma, resistance to}, 254500Severe combined immunodeficiency with sensitivity to ionizing radiation, 602450; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Fetal anomalies v3.167 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SEVERE COMBINED IMMUNODEFICIENCY AUTOSOMAL RECESSIVE T-CELL-NEGATIVE/B-CELL-NEGATIVE/NK-CELL-POSITIVE WITH SENSITIVITY TO IONIZING RADIATION; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Cytopenia - NOT Fanconi anaemia v3.34 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from 606593 LIG4 syndrome to LIG4 syndrome, OMIM:606593
IUGR and IGF abnormalities v1.68 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from microcephaly, growth retardation, immunodeficiency, developmental delay to LIG4 syndrome, OMIM:606593; microcephaly, growth retardation, immunodeficiency, developmental delay
Haematological malignancies for rare disease v1.18 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL to LIG4 syndrome, OMIM:606593; Class: miscellaneous; Ligase IV syndrome; Lymphoma; ALL
Infantile enterocolitis & monogenic inflammatory bowel disease v1.44 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from SCID; LIG4 syndrome 606593 to LIG4 syndrome, OMIM:606593
Severe microcephaly v4.85 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from MPD; microcephalic primordial dwarfism; LIG4 syndrome, 606593; microcephaly to LIG4 syndrome, OMIM:606593; Microcephalic primordial dwarfism
Intellectual disability v5.546 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1, 224690; MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Skeletal dysplasia v4.65 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 224690; Meier-Gorlin syndrome 1 224690 to Meier-Gorlin syndrome 1, OMIM:224690
Fetal anomalies v3.166 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Limb disorders v4.22 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690
Deafness and congenital structural abnormalities v1.27 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Bilateral Microtia; 224690; Meier Gorlin EPS; causes microtia and syndromic features; Meier-Gorlin syndrome 1 to Meier-Gorlin syndrome 1, OMIM:224690; Bilateral Microtia
IUGR and IGF abnormalities v1.67 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia to Meier-Gorlin syndrome 1, OMIM:224690; microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia
Severe microcephaly v4.84 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 1, 224690 to Meier-Gorlin syndrome 1, OMIM:224690; Microcephalic primordial dwarfism
Intellectual disability v5.545 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Fetal anomalies v3.165 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MEIER-GORLIN SYNDROME 2 to Meier-Gorlin syndrome 2, OMIM:613800
Skeletal dysplasia v4.64 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2 613800; Meier-Gorlin syndrome 2 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Deafness and congenital structural abnormalities v1.26 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Bilateral Microtia; 613800; Meier-Gorlin EPS; causes syndromic features to Meier-Gorlin syndrome 2, OMIM:613800; Bilateral Microtia
IUGR and IGF abnormalities v1.66 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 2, OMIM:613800; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.83 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800; Microcephalic primordial dwarfism
Breast cancer pertinent cancer susceptibility v2.8 PTEN Dmitrijs Rots reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PHTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.31 COASY Achchuthan Shanmugasundram Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.30 COASY Achchuthan Shanmugasundram Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; Pontocerebellar hypoplasia, type 12, OMIM:618266; arthrogryposis, MONDO:0008779
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: COASY.
Tag Q2_24_NHS_review tag was added to gene: COASY.
Arthrogryposis v5.29 COASY Achchuthan Shanmugasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 30089828, 35499143, 36495139; Phenotypes: Neurodegeneration with brain iron accumulation 6, OMIM:615643, Pontocerebellar hypoplasia, type 12, OMIM:618266, arthrogryposis, MONDO:0008779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.29 PIP5K1C Achchuthan Shanmugasundram Phenotypes for gene: PIP5K1C were changed from Lethal congenital contractural syndrome 3 611369 to Lethal congenital contractural syndrome 3, OMIM:611369
Arthrogryposis v5.28 PIP5K1C Achchuthan Shanmugasundram Publications for gene: PIP5K1C were set to 17701898
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are three unrelated cases with biallelic variants (two unrelated cases with the same homozygous variant and two foetuses from one family with compound heterozygous variants), this gene can be promoted to green rating in the next GMS update.
Arthrogryposis v5.27 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PIP5K1C.
Tag Q2_24_NHS_review tag was added to gene: PIP5K1C.
Arthrogryposis v5.26 PIP5K1C Achchuthan Shanmugasundram reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 17701898, 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 TRIP4 Achchuthan Shanmugasundram reviewed gene: TRIP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866, ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.26 COASY Achchuthan Shanmugasundram Publications for gene: COASY were set to 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
Ectodermal dysplasia v3.29 TWIST2 Dmitrijs Rots gene: TWIST2 was added
gene: TWIST2 was added to Ectodermal dysplasia. Sources: Expert Review
Mode of inheritance for gene: TWIST2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWIST2 were set to Focal facial dermal dysplasia 3, Setleis type
Review for gene: TWIST2 was set to GREEN
Added comment: Included as differential for ectodermal dysplasia
Sources: Expert Review
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Classified gene: SLC18A3 as Amber List (moderate evidence)
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, PMID:34943989 reports an additional patient with compound heterozygous variants in SLC18A3 gene and presenting with arthrogryposis congenital (AMC). Hence, there is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Arthrogryposis v5.25 SLC18A3 Achchuthan Shanmugasundram Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC18A3.
Tag Q2_24_NHS_review tag was added to gene: SLC18A3.
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram edited their review of gene: SLC18A3: Changed phenotypes to: Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239, arthrogryposis, MONDO:0008779
Arthrogryposis v5.24 SLC18A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC18A3 were changed from Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis to Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239; arthrogryposis, MONDO:0008779
Arthrogryposis v5.23 SLC18A3 Achchuthan Shanmugasundram Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209
Arthrogryposis v5.22 SLC18A3 Achchuthan Shanmugasundram reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.63 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3 613803; Meier-Gorlin syndrome 3 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Intellectual disability v5.544 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Fetal anomalies v3.164 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MEIER-GORLIN SYNDROME 3 to Meier-Gorlin syndrome 3, OMIM:613803
Deafness and congenital structural abnormalities v1.25 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Bilateral Microtia; 613803; Meier-Gorlin EPS; causes syndromic features; Meier-Gorlin syndrome 3 to Meier-Gorlin syndrome 3, OMIM:613803; Bilateral Microtia
IUGR and IGF abnormalities v1.65 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia to Meier-Gorlin syndrome 3, OMIM:613803; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia
Severe microcephaly v4.82 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803; Microcephalic primordial dwarfism
Insulin resistance (including lipodystrophy) v1.17 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720; Osteodysplastic Primordial Dwarfism of Majewski Tyoe 2; Severe Insulin Resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Insulin resistance, HP:0000855
IUGR and IGF abnormalities v1.64 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Limb disorders v4.21 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Skeletal dysplasia v4.62 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
DDG2P v3.88 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Fetal anomalies v3.163 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Intellectual disability v5.543 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, 210720 -3; MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Severe microcephaly v4.81 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MPD; microcephalic primordial dwarfism; Microcephalic Osteodysplastic Primordial Dwarfism; Microcephalic osteodysplastic primordial dwarfism, type II, 210720 to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Microcephalic primordial dwarfism
Retinal disorders v4.90 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651 to Lowry-Wood syndrome, OMIM:226960; Roifman syndrome, OMIM:616651
Intellectual disability v5.542 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Gene2Phenotype confirmed gene with ID HPO to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Early onset or syndromic epilepsy v4.196 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Fetal anomalies v3.162 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710
Cytopenia - NOT Fanconi anaemia v3.33 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome, 616651; Microcephalic osteodysplastic primordial dwarfism, type I, 210710 to Roifman syndrome, OMIM:616651
Bleeding and platelet disorders v3.10 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I / Roifman syndrome to Roifman syndrome, OMIM:616651
Inherited bleeding disorders v1.178 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Platelet disorder; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency to Roifman syndrome, OMIM:616651; Roifman Syndrome with thrombocytopenia and Primary immunodeficiency
Skeletal dysplasia v4.61 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Roifman syndrome 616651; Microcephalic osteodysplastic primordial dwarfism, type I 210710 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Limb disorders v4.20 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I 210710; Roifman syndrome 616651 to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Primary immunodeficiency or monogenic inflammatory bowel disease v4.202 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
COVID-19 research v1.142 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly
Severe microcephaly v4.80 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I; Microcephalic osteodysplastic primordial dwarfism, type I, 210710; MPD; microcephalic primordial dwarfism to Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Lowry-Wood syndrome, OMIM:226960; Microcephalic primordial dwarfism
Intellectual disability v5.541 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9, 616777 to Seckel syndrome 9, OMIM:616777
Cerebral vascular malformations v3.16 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 616777 to Seckel syndrome 9, OMIM:616777
Fetal anomalies v3.161 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9 to Seckel syndrome 9, OMIM:616777
Severe microcephaly v4.79 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 9, 616777; Microcephaly to Seckel syndrome 9, OMIM:616777; Microcephalic primordial dwarfism
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Mode of inheritance for gene: XRCC4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.169 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Fetal anomalies v3.160 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Skeletal dysplasia v4.60 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Intellectual disability v5.540 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
IUGR and IGF abnormalities v1.63 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism
Severe microcephaly v4.78 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from MPD; microcephalic primordial dwarfism; Short stature, microcephaly, and endocrine dysfunction, 616541 to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541; Microcephalic primordial dwarfism
Severe microcephaly v4.77 ATRIP Arina Puzriakova Publications for gene: ATRIP were set to
Severe microcephaly v4.76 ATRIP Arina Puzriakova Mode of inheritance for gene: ATRIP was changed from to BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.75 ATRIP Arina Puzriakova Phenotypes for gene: ATRIP were changed from MPD; microcephalic primordial dwarfism; severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism to Microcephalic primordial dwarfism; Severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism
Intellectual disability v5.539 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Skeletal dysplasia v4.59 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Meier-Gorlin syndrome 5 613805 to Meier-Gorlin syndrome 5, OMIM:613805
Fetal anomalies v3.159 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Deafness and congenital structural abnormalities v1.24 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from Bilateral Microtia; 613805; Meier-Gorlin syndrome 5, 613805; Neurology panel; Bilateral Microtia, 613805; Causes Meier-Gorlin EPS; syndromic features to Meier-Gorlin syndrome 5, OMIM:613805; Bilateral Microtia
IUGR and IGF abnormalities v1.62 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia to Meier-Gorlin syndrome 5, OMIM:613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia
Severe microcephaly v4.74 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MPD; microcephalic primordial dwarfism; ?Meier-Gorlin syndrome 5, 613805 to Meier-Gorlin syndrome 5, OMIM:613805; Microcephalic primordial dwarfism
Severe microcephaly v4.73 CENPE Arina Puzriakova Phenotypes for gene: CENPE were changed from ?Microcephaly 13, primary, autosomal recessive, 616051; MPD; microcephalic primordial dwarfism to ?Microcephaly 13, primary, autosomal recessive, OMIM:616051; Microcephalic primordial dwarfism
Intellectual disability v5.538 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Skeletal dysplasia v4.58 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Meier-Gorlin syndrome 4 613804 to Meier-Gorlin syndrome 4, OMIM:613804
Fetal anomalies v3.158 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Deafness and congenital structural abnormalities v1.23 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from Bilateral Microtia; 613804; Meier-Gorlin syndrome 4, 613804; Causes Meier-Gorlin EPS; syndromic features; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge to Meier-Gorlin syndrome 4, OMIM:613804; Short stature, small head size, the ears may be low-set or rotated backward (+/-microtia). Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge
IUGR and IGF abnormalities v1.61 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia to Meier-Gorlin syndrome 4, OMIM:613804; micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia
Severe microcephaly v4.72 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MPD; microcephalic primordial dwarfism; Meier-Gorlin syndrome 4, 613804 to Meier-Gorlin syndrome 4, OMIM:613804; Microcephalic primordial dwarfism
Monogenic diabetes v2.58 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Pigmentary skin disorders v3.12 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome to Bloom syndrome, OMIM:210900
Primary ovarian insufficiency v1.68 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome 210900 to Bloom syndrome, OMIM:210900
IUGR and IGF abnormalities v1.60 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900 to Bloom syndrome, OMIM:210900
Haematological malignancies for rare disease v1.17 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas to Bloom syndrome, OMIM:210900; Class: BM failure syndrome (typ AR); Bloom syndrome; leukaemia; lymphoma; skin squamous cell; other tumour types; Lymphoma; ALL; MDS; AML; Leukaemia; Carcinomas
Severe microcephaly v4.71 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, OMIM:210900 to Bloom syndrome, OMIM:210900; Microcephalic primordial dwarfism
Hereditary haemorrhagic telangiectasia v3.6 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Cutaneous telangiectasia and cancer syndrome, familial, 614564 (biallelic) to ?Cutaneous telangiectasia and cancer syndrome, familial, OMIM:614564
Intellectual disability v5.537 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Seckel syndrome 1, 210600Cutaneous telangiectasia and cancer syndrome, familial, 614564; SECKEL SYNDROME TYPE 1 (SCKL1) to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME 1; SCKL1 to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Mode of inheritance for gene: ATR was changed from to BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.70 ATR Arina Puzriakova Publications for gene: ATR were set to
Severe microcephaly v4.69 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from MPD; microcephalic primordial dwarfism; Seckel syndrome 1, 210600; MICROCEPHALIC PRIMORDIAL DWARFISM I to Seckel syndrome 1, OMIM:210600; Microcephalic primordial dwarfism
Intellectual disability v5.536 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications to: 31036916, 38465576; Changed phenotypes to: Syndromic disease MONDO:0002254, FEM1B-related
Fetal anomalies v3.157 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Intellectual disability v5.536 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Over 100 individuals reported with NND and heterozygous variants in a 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III). The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). Variants in this region likely explain 0.41% of individuals with NDD.
Sources: Literature
Intellectual disability v5.536 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Intellectual disability v5.536 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Childhood onset hereditary spastic paraplegia v4.43 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Severe microcephaly v4.68 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric disorders - additional genes v3.10 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.157 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Fetal anomalies v3.157 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Fetal anomalies v3.157 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Paediatric disorders - additional genes v3.9 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Classified gene: PLD1 as Green List (high evidence)
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.
Paediatric or syndromic cardiomyopathy v3.47 PLD1 Arina Puzriakova Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v3.156 PLD1 Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel:

Jesse Hayesmoore (Oxford Regional Genetics Laboratory)
Red List (low evidence)

"On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines."
Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m
Paediatric or syndromic cardiomyopathy v3.46 PLD1 Arina Puzriakova Tag Q2_24_demote_red tag was added to gene: PLD1.
Tag Q2_24_expert_review tag was added to gene: PLD1.
Tag Q2_24_NHS_review tag was added to gene: PLD1.
Early onset or syndromic epilepsy v4.195 GLI3 Arina Puzriakova Mode of inheritance for gene: GLI3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.194 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Skeletal ciliopathies v3.22 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Childhood onset dystonia, chorea or related movement disorder v3.76 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Neurological ciliopathies v3.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Ophthalmological ciliopathies v3.6 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Rare multisystem ciliopathy disorders v1.171 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Joubert Syndrome and Senior-Loken Syndrome 24 gene panel to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Clefting v4.109 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome, 146510 to Pallister-Hall syndrome, OMIM:146510
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.180 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; 175700 to Greig cephalopolysyndactyly syndrome, OMIM:175700
Unexplained young onset end-stage renal disease v3.41 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome; Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
CAKUT v1.176 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome to Pallister-Hall syndrome, OMIM:146510
Unexplained kidney failure in young people v1.119 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome 146510 to Pallister-Hall syndrome, OMIM:146510
Fetal anomalies v3.156 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from PALLISTER-HALL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; PREAXIAL POLYDACTYLY TYPE IV; POSTAXIAL POLYDACTYLY TYPE A to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Skeletal dysplasia v4.57 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; Pallister-Hall syndrome 146510; {Hypothalamic hamartomas, somatic} 241800 to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Limb disorders v4.19 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome 175700; Pallister-Hall syndrome 146510; Polydactyly, postaxial, types A1 and B 174200; Polydactyly, preaxial, type IV 174700; {Hypothalamic hamartomas, somatic} 241800; Polydactyly to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510; Polydactyly, postaxial, types A1 and B, OMIM:174200; Polydactyly, preaxial, type IV, OMIM:174700
Pituitary hormone deficiency v3.12 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome (175700); Pallister-Hall syndrome (146510) to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.535 GLI3 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: GLI3.
Tag Q2_24_NHS_review tag was added to gene: GLI3.
Intellectual disability v5.535 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome, 175700Pallister-Hall syndrome, 146510Polydactyly, preaxial, type IV, 174700Polydactyly, postaxial, types A1 and B, 174200{Hypothalamic hamartomas, somatic}, 241800; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.534 GLI3 Arina Puzriakova Publications for gene: GLI3 were set to
Intellectual disability v5.533 GLI3 Arina Puzriakova Classified gene: GLI3 as Green List (high evidence)
Intellectual disability v5.533 GLI3 Arina Puzriakova Added comment: Comment on list classification: Reassessed in view of the Red review by Tracy Lester on this Green gene

Rarely, individuals with Greig cephalopolysyndactyly syndrome or GLI3-Related Pallister-Hall syndrome have been found to have intellectual disability (PMID: 12414818; 14708104; 14608643; 34296525). This is usually observed in the most severely affected individuals and those with large deletions encompassing GLI3. The majority of patients have normal psychomotor development or only some mild delays. All GLI3-related disorders are more likely to be recognised in context of other features such as skeletal abnormalities.

Overall, I therefore agree that this gene could be demoted to Amber at the next GMS panel update.
Intellectual disability v5.533 GLI3 Arina Puzriakova Gene: gli3 has been classified as Green List (High Evidence).
Pigmentary skin disorders v3.11 BLM Dmitrijs Rots gene: BLM was added
gene: BLM was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLM were set to PMID: 32972601
Phenotypes for gene: BLM were set to Bloom syndrome
Penetrance for gene: BLM were set to Complete
Review for gene: BLM was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Pigmentary skin disorders v3.11 SMARCB1 Dmitrijs Rots gene: SMARCB1 was added
gene: SMARCB1 was added to Pigmentary skin disorders. Sources: Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to PMID: 32972601
Phenotypes for gene: SMARCB1 were set to Schwannomatosis-1, susceptibility to
Penetrance for gene: SMARCB1 were set to Incomplete
Review for gene: SMARCB1 was set to GREEN
Added comment: Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review
Intellectual disability v5.532 CPA6 Arina Puzriakova Tag refuted tag was added to gene: CPA6.
Intellectual disability v5.532 CPA6 Arina Puzriakova commented on gene: CPA6
Severe microcephaly v4.67 SASS6 Zornitza Stark edited their review of gene: SASS6: Added comment: Two additional families:

PMID: 38501757
1x compound het for a fs and +3 splice variant.

Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed; Changed rating: GREEN; Changed publications to: 24951542, 30639237, 38501757, 36739862
Intellectual disability v5.532 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability v5.532 GTF3C5 Zornitza Stark gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected mechanism.
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Intellectual disability v5.532 DOCK4 Zornitza Stark gene: DOCK4 was added
gene: DOCK4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK4 were set to 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Literature
Intellectual disability v5.532 PLXNB2 Zornitza Stark gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752
Phenotypes for gene: PLXNB2 were set to Syndromic disease MONDO:0002254, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KIAA1024L.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Classified gene: KIAA1024L as Amber List (moderate evidence)
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Gene: kiaa1024l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram commented on gene: KIAA1024L: The new gene name for KIAA1024L is MINAR2 and 'new-gene-name' tag has been added to flag this.
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Monogenic hearing loss. Sources: Literature
new-gene-name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Intellectual disability v5.532 CEP295 Zornitza Stark edited their review of gene: CEP295: Changed rating: GREEN
Intellectual disability v5.532 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Expert Review
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Classified gene: ATP2B3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.62 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Ataxia and cerebellar anomalies - narrow panel v4.61 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Ataxia and cerebellar anomalies - narrow panel v4.60 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ATP2B3.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.; to: There are six unrelated cases reported with five different X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.; to: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.34 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1; X-linked spinocerebellar ataxia, 302500 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.33 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Hereditary ataxia with onset in adulthood v4.32 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram commented on gene: ATP2B3: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood inn three of these cases, while detailed clinical information was not available for the other three cases.
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram edited their review of gene: ATP2B3: Changed phenotypes to: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Hereditary ataxia with onset in adulthood v4.31 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram changed review comment from: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs )were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795).; to: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs) were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795). Hence the rating should remain amber with current evidence.
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Classified gene: MAX as Amber List (moderate evidence)
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by James Poulter, there is sufficient evidence available (three unrelated cases with the same p.Arg60Gln variant and functional studies) for the promotion of this gene to green rating in the next GMS update.
Neurological segmental overgrowth v2.12 MAX Achchuthan Shanmugasundram Gene: max has been classified as Amber List (Moderate Evidence).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram changed review comment from: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.

This gene has been associated with relevant phenotypes in OMIM (MIM #620712).
Neurological segmental overgrowth v2.11 MAX Achchuthan Shanmugasundram Phenotypes for gene: MAX were changed from Macrocephaly; Polydactyly; delayed ophthalmic development; autism to Polydactyly-macrocephaly syndrome, OMIM:620712
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MAX.
Tag Q2_24_NHS_review tag was added to gene: MAX.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram changed review comment from: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.; to: PMID:38141607 reported three individuals with the same recurrent de novo germline variant in the MAX gene (p.Arg60Gln). Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.10 MAX Achchuthan Shanmugasundram Publications for gene: MAX were set to PMID:38141607
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram commented on gene: MAX: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Neurological segmental overgrowth v2.9 MAX Achchuthan Shanmugasundram reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Polydactyly-macrocephaly syndrome, OMIM:620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #301118), but not yet in Gene2Phenotype.
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Ian Berry, there are now at least nine probands with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CADM3.
Tag Q2_24_NHS_review tag was added to gene: CADM3.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Classified gene: CADM3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.93 CADM3 Achchuthan Shanmugasundram Publications for gene: CADM3 were set to 33889941
Hereditary neuropathy or pain disorder v3.92 CADM3 Achchuthan Shanmugasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.36 GRXCR2 Sadaf Naz reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33528103, PMID:24619944; Phenotypes: #615837: Deafness, autosomal recessive 101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Classified gene: CASZ1 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ludmila Volozonoka, there is sufficient evidence available (three unrelated cases and some functional studies) for the promotion of this gene to green rating in the next GMS update.
Paediatric or syndromic cardiomyopathy v3.46 CASZ1 Achchuthan Shanmugasundram Gene: casz1 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v3.45 CASZ1 Achchuthan Shanmugasundram Phenotypes for gene: CASZ1 were changed from Pediatric Dilated Cardiomyopathy; Pediatric LVNC to dilated cardiomyopathy, MONDO:0005021; left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram changed review comment from: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.; to: PMID:28099117 reported a patient with a novel heterozygous CASZ1 variant (p.K351X) and with dilated cardiomyopathy (DCM). The variant co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The functional characterisation of the variant with a luciferase reporter assay showed that the variant had no transcriptional activity.

PMID:31268246 reported the identification of a previously unreported de novo heterozygous frameshift variant (p.Val815Profs*14) in CASZ1 in an 11-month-old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC).

PMID:36293425 reported a girl with a new de novo frameshift variant (p.Trp1261GlyfsTer29) in CASZ1 gene. DCM was diagnosed for the first time at the age of three months and she died at the age of 1 year 10 months with a diagnosis of dilated cardiomyopathy and decompensation, systemic multiple organ failure, post-anoxic brain damage and gastrointestinal and vaginal bleeding.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram edited their review of gene: CASZ1: Changed phenotypes to: dilated cardiomyopathy, MONDO:0005021, left ventricular noncompaction, MONDO:0018901
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: CASZ1.
Paediatric or syndromic cardiomyopathy v3.44 CASZ1 Achchuthan Shanmugasundram reviewed gene: CASZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28099117, 31268246, 36293425; Phenotypes: dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.89 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: MT-ATP6.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SLC37A3.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Classified gene: SLC37A3 as Amber List (moderate evidence)
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Retinal disorders v4.89 SLC37A3 Achchuthan Shanmugasundram Gene: slc37a3 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.88 SLC37A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC37A3 were changed from Retinitis pigmentosa; No OMIM entry to retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.87 SLC37A3 Achchuthan Shanmugasundram Publications for gene: SLC37A3 were set to 28041643
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SLC37A3.
Retinal disorders v4.86 SLC37A3 Achchuthan Shanmugasundram reviewed gene: SLC37A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MT-ATP6.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Classified gene: MT-ATP6 as Amber List (moderate evidence)
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is ample evidence available for the association of MT-ATP6 gene with retinitis pigmentosa. Hence, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.86 MT-ATP6 Achchuthan Shanmugasundram Gene: mt-atp6 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.85 MT-ATP6 Achchuthan Shanmugasundram Phenotypes for gene: MT-ATP6 were changed from Retinitis pigmentosa to NARP syndrome, MONDO:0010794
Retinal disorders v4.84 MT-ATP6 Achchuthan Shanmugasundram Publications for gene: MT-ATP6 were set to
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: MT-ATP6.
Retinal disorders v4.83 MT-ATP6 Achchuthan Shanmugasundram reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11843698, 17568559, 19124644, 22819295, 23266623, 24118886, 27015314, 29054413, 29224958, 36809201; Phenotypes: NARP syndrome, MONDO:0010794; Mode of inheritance: MITOCHONDRIAL
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Classified gene: PTCRA as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.201 PTCRA Achchuthan Shanmugasundram Gene: ptcra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.200 PTCRA Achchuthan Shanmugasundram Phenotypes for gene: PTCRA were changed from Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PTCRA.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 PTCRA Achchuthan Shanmugasundram reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 38422122; Phenotypes: Autoimmunity, HP:0002960, lymphopenia, MONDO:0003783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.92 GAN Arina Puzriakova Publications for gene: GAN were set to 1106248
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update as the scope of this panel has now been expanded to include complex cases of neuropathy.
Biallelic variants in the GAN gene cause giant axonal neuropathy. This childhood onset polyneuropathy results in progressive neurodegeneration of both the peripheral and central nervous systems. More than 10 unrelated cases have been reported in the literature which is sufficient for making this gene Green (PMIDs: 18595793; 19231187; 20949505; 27852232; 36866531)
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.531 GAN Arina Puzriakova changed review comment from: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.531 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Intellectual disability v5.531 GAN Arina Puzriakova Publications for gene: GAN were set to
Intellectual disability v5.530 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Intellectual disability v5.530 GAN Arina Puzriakova Added comment: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.530 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.22 COASY Hannah Knight reviewed gene: COASY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35499143; Phenotypes: Pontocerebellar hypoplasia type 12; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 PIP5K1C Hannah Knight reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38491417; Phenotypes: Lethal congenital contractural syndrome 3 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Arthrogryposis v5.22 SLC18A3 Hannah Knight reviewed gene: SLC18A3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34943989; Phenotypes: Myasthenic syndrome, congenital, 21, presynaptic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 TRIP4 Hannah Knight reviewed gene: TRIP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31794073; Phenotypes: Spinal muscular atrophy with congenital bone fractures 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.529 GAN Arina Puzriakova Mode of inheritance for gene: GAN was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.528 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy v1.477 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.525 SEPHS1 Arina Puzriakova gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_24_promote_green tags were added to gene: SEPHS1.
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SEPHS1 was set to GREEN
Added comment: Mullegama et al. (2024) reported 9 individuals from 8 families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight individuals shared different missense variants at the same p.Arg371 residue in SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were confirmed as de novo (one unknown). Functional studies showed that variants at the Arg371 residue impact direct protein-protein interactions of SEPSH1 and enhance cell proliferation by modulating ROS homeostasis.
Sources: Literature
Fetal anomalies v3.155 GRM1 Arina Puzriakova Classified gene: GRM1 as Red List (low evidence)
Fetal anomalies v3.155 GRM1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Zornitza Stark. Could not find any evidence of prenatal phenotypes in patients with GRM1 variants.
Fetal anomalies v3.155 GRM1 Arina Puzriakova Gene: grm1 has been classified as Red List (Low Evidence).
Stickler syndrome v4.4 LRP2 Arina Puzriakova Classified gene: LRP2 as Red List (low evidence)
Stickler syndrome v4.4 LRP2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Only a single family reported with features overlapping those of Stickler syndrome (PMID:23992033), mainly based on their ocular phenotype, including high myopia, vitreous changes, cataract and esotropia. LRP2 variants are typically associated with Donnai-Barrow syndrome and facio-oculo-acoustico-renal syndrome which are not relevant to this panel.
Stickler syndrome v4.4 LRP2 Arina Puzriakova Gene: lrp2 has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Classified gene: FCGR3B as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.

Also note review from Helen Brittain (Genomics England Clinical Team) on 100K panel Cytopenias and congenital anaemias (159) from 9 Mar 2017:

"Relevant phenotype affects neutrophils only, on a transient basis owing to presence of antibodies in mother and antigen in fetus (as a result of different genetic factors in father and mother.). Therefore not a germline condition associated with mutations in the child."
Cytopenia - NOT Fanconi anaemia v3.32 FCGR3B Arina Puzriakova Gene: fcgr3b has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Classified gene: ADAMTS2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.19 ADAMTS2 Arina Puzriakova Gene: adamts2 has been classified as Red List (Low Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: MYZAP.
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Deleted their comment
Dilated and arrhythmogenic cardiomyopathy v2.22 MYZAP Arina Puzriakova Publications for gene: MYZAP were set to 34899865; 20093627; 35840178
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Classified gene: MYZAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.
Dilated and arrhythmogenic cardiomyopathy v2.21 MYZAP Arina Puzriakova Gene: myzap has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Classified gene: NDNF as Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Added comment: Comment on list classification: Gene was re-reviewed in light of an Amber review by Zornitza Stark (Australian Genomics) on a Green gene. At least five unrelated cases have been reported, as well as mouse and zebrafish studies showing Ndnf deficiency leads to anomalies in GnRH neuron migration. Pedigree analysis does indicate variable expressivity and incomplete penetrance, although this is relatively common in dominant forms of HH. Furthermore, inclusion of NDNF on this panel has already been reviewed and approved by the NHS specialist group and therefore the Green rating is being maintained.
Hypogonadotropic hypogonadism (GMS) v3.18 NDNF Arina Puzriakova Gene: ndnf has been classified as Green List (High Evidence).
Hypogonadotropic hypogonadism (GMS) v3.17 NDNF Arina Puzriakova Phenotypes for gene: NDNF were changed from Congenital hypogonadotropic hypogonadism (CHH); Hypogonadotropic hypogonadism 25 with anosmia, 618841 to Hypogonadotropic hypogonadism 25 with anosmia, OMIM:618841
Hypogonadotropic hypogonadism (GMS) v3.16 NDNF Arina Puzriakova Publications for gene: NDNF were set to 31883645
Hypogonadotropic hypogonadism (GMS) v3.15 NDNF Arina Puzriakova commented on gene: NDNF: PMID: 36245975 (2022) - another male patient with idiopathic hypogonadotropin hypogonadism identified harbouring a paternally inherited NDNF variant (c.1439T>A, p.Ile480Asn)
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Hereditary spastic paraplegia v1.311 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.310 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Hereditary spastic paraplegia v1.309 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to Montenegro et al. (2012)
Hereditary spastic paraplegia v1.308 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.
Childhood onset hereditary spastic paraplegia v4.42 RTN2 Achchuthan Shanmugasundram Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset hereditary spastic paraplegia v4.41 RTN2 Achchuthan Shanmugasundram Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805 to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Childhood onset hereditary spastic paraplegia v4.40 RTN2 Achchuthan Shanmugasundram Publications for gene: RTN2 were set to 22232211; 24123792; 28362824
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram Tag Q2_24_MOI tag was added to gene: RTN2.
Tag Q2_24_NHS_review tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894, Lower limb spasticity, HP:0002061; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Classified gene: COL5A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.18 COL5A2 Arina Puzriakova Gene: col5a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Classified gene: COL5A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.17 COL5A1 Arina Puzriakova Gene: col5a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Classified gene: COL4A5 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.16 COL4A5 Arina Puzriakova Gene: col4a5 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Classified gene: COL4A4 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.15 COL4A4 Arina Puzriakova Gene: col4a4 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Classified gene: COL4A3 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.14 COL4A3 Arina Puzriakova Gene: col4a3 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Classified gene: COL3A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.13 COL3A1 Arina Puzriakova Gene: col3a1 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Classified gene: COL1A2 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.12 COL1A2 Arina Puzriakova Gene: col1a2 has been classified as Red List (Low Evidence).
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Classified gene: COL1A1 as Red List (low evidence)
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Dmitrijs Rots.
Rare genetic inflammatory skin disorders v3.11 COL1A1 Arina Puzriakova Gene: col1a1 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Tag watchlist tag was added to gene: IL17RA.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Classified gene: IL17RA as Amber List (moderate evidence)
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants have been found patients with immunodeficiency, presenting as chronic mucocutaneous candidiasis (PMID: 21350122).

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine implicated in diverse autoimmune and inflammatory disorders such as psoriasis and Kawasaki disease so it is plausible that the interleukin-17A receptor (IL-17RA) could contribute to the same pathway.

Literature review did reveal multiple mouse models where IL-17RA was shown to promote the inflammatory response (PMID: 38060620; 30364284; 35844540; 38451335); however, there is no evidence of human cases where a variant in the IL17RA gene caused an autoinflammatory disorder. Therefore rating as Amber with a watchlist tag, awaiting further evidence.
Autoinflammatory disorders v1.17 IL17RA Arina Puzriakova Gene: il17ra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Candidiasis, familial, 5;Chronic mucocutaneous candidiasis (CMC);Immunodeficiency 51, 613953;Defects in Intrinsic and Innate Immunity;CMC, folliculitis;Defects in Intrinsic and Innate Immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.199 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Candidiasis, familial, 5; Chronic mucocutaneous candidiasis (CMC); Immunodeficiency 51, 613953; Defects in Intrinsic and Innate Immunity; CMC, folliculitis; Defects in Intrinsic and Innate Immunity to Immunodeficiency 51, OMIM:613953
Autoinflammatory disorders v1.16 IL17RA Arina Puzriakova Phenotypes for gene: IL17RA were changed from Immunodeficiency-51 to Immunodeficiency 51, OMIM:613953
Likely inborn error of metabolism v4.137 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism v4.137 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Likely inborn error of metabolism v4.136 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism v4.136 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted);Severe combined immunodeficiency due to ADA deficiency, 102700;T-B- SCID;T-B+ SCID;Adenosine deaminase (ADA) deficiency;Atypical Severe Combined Immunodeficiency (Atypical SCID);Omenn syndrome;Severe combined immunodeficiency (SCID);Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects;Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.198 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted); Severe combined immunodeficiency due to ADA deficiency, 102700; T-B- SCID; T-B+ SCID; Adenosine deaminase (ADA) deficiency; Atypical Severe Combined Immunodeficiency (Atypical SCID); Omenn syndrome; Severe combined immunodeficiency (SCID); Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects; Immunodeficiencies affecting cellular and humoral immunity to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.154 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Fetal anomalies v3.153 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from ADENOSINE DEAMINASE DEFICIENCY to Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Adenosine deaminase deficiency (Disorders of purine metabolism);Combined B and T cell defect;Infantile enterocolitis & monogenic inflammatory bowel disease;SCID
Undiagnosed metabolic disorders v1.617 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Adenosine deaminase deficiency (Disorders of purine metabolism); Combined B and T cell defect; Infantile enterocolitis & monogenic inflammatory bowel disease; SCID to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Intellectual disability v5.524 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, 102700; Adenosine deaminase deficiency, partial, 102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.3 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700
Severe combined immunodeficiency with adenosine deaminase deficiency v1.2 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Autoinflammatory disorders v1.15 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from T(-), B(-), NK(-) severe combin immunodeficiency to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Bleeding and platelet disorders v3.9 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from 614201 Bleeding disorder, platelet-type, 11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Inherited bleeding disorders v1.177 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Bleeding diathesis due to glycoprotein VI deficiency to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.14 GP6 Arina Puzriakova Phenotypes for gene: GP6 were changed from Platlet-type bleeding disorder-11 to Bleeding disorder, platelet-type, 11, OMIM:614201
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Classified gene: GP6 as Red List (low evidence)
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with bleeding disorder caused by defective platelet activation and aggregation in response to collagen. Could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.13 GP6 Arina Puzriakova Gene: gp6 has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Classified gene: ADA as Red List (low evidence)
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with partial ADA deficiency or severe combined immunodeficiency (SCID) due to ADA deficiency with multiple unrelated cases reported.

Despite ADA null mice displaying severe pulmonary inflammation, could not find evidence of an autoinflammatory component observed in patients and therefore rating as Red on this panel
Autoinflammatory disorders v1.12 ADA Arina Puzriakova Gene: ada has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Classified gene: RTN2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of RTN2 biallelic variants with distal hereditary motor neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Gene: rtn2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: RTN2.
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram gene: RTN2 was added
gene: RTN2 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN2 were set to 38527963
Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894
Review for gene: RTN2 was set to GREEN
Added comment: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Fetal anomalies v3.152 NRXN2 Sarah Leigh Classified gene: NRXN2 as Red List (low evidence)
Fetal anomalies v3.152 NRXN2 Sarah Leigh Added comment: Comment on list classification: There insufficient evidence between NRXN2 variants and autism for this gene to be rated amber.
Fetal anomalies v3.152 NRXN2 Sarah Leigh Gene: nrxn2 has been classified as Red List (Low Evidence).
Iron metabolism disorders - NOT common HFE mutations v2.6 CYBRD1 Sarah Leigh Publications for gene: CYBRD1 were set to 15338274; 27884173
Iron metabolism disorders - NOT common HFE mutations v2.5 CYBRD1 Sarah Leigh edited their review of gene: CYBRD1: Added comment: It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).; Changed rating: AMBER
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent heterozygous LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Tag recurrent-variant tag was added to gene: LIM2.
Tag Q2_24_MOI tag was added to gene: LIM2.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.; to: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant (PMIDs: 32202185; 33078099; 33708862; 33923544; 35736209). These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Added comment: Comment on mode of inheritance: The MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. At least 9 unrelated multigenerational families have been identified with congenital cataracts due to a recurrent LIM2 p.R130C variant. These families come from different ancestries (British, Chinese, Spanish, Japanese) and haplotype analysis in families from shared ancestries has suggested the variant likely arose due to independent founder events in each family. The evidence therefore supports this MOI being included in future analyses.
Bilateral congenital or childhood onset cataracts v4.12 LIM2 Arina Puzriakova Mode of inheritance for gene: LIM2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.87 CADM3 Ian Berry reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38074074, 33889941; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts v4.11 LIM2 Arina Puzriakova Publications for gene: LIM2 were set to Ponnam et al (2008) Mol Vis 14:1204-1208; Pras et al (2002) Am J Hum genet 70:1363-7
Bilateral congenital or childhood onset cataracts v4.10 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cortical Pulverulent Cataract; Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Structural eye disease v3.77 LIM2 Arina Puzriakova Phenotypes for gene: LIM2 were changed from Cataract 19, 615277 to Cataract 19, multiple types, OMIM:615277
Intellectual disability v5.523 FRYL Arina Puzriakova Classified gene: FRYL as Amber List (moderate evidence)
Intellectual disability v5.523 FRYL Arina Puzriakova Added comment: Comment on list classification: Rating Amber as overall the evidence is borderline. Only one recent study (PMID:38479391) has reported an disease association for FRYL, with variable phenotypes and results from functional studies, as well as variants in other genes in several cases. Additional studies are required to conclusively corroborate causality (added watchlist tag).
Intellectual disability v5.523 FRYL Arina Puzriakova Gene: fryl has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.522 FRYL Arina Puzriakova gene: FRYL was added
gene: FRYL was added to Intellectual disability - microarray and sequencing. Sources: Literature
watchlist tags were added to gene: FRYL.
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: FRYL was set to AMBER
Added comment: New association linking this gene to disease which is not yet listed in OMIM or Gene2Phenotype. There are no sequence variants in Decipher and ClinVar shows only a single pathogenic frameshift variant (c.1224del, p.Lys409fs) for FRYL-associated neurodevelopmental disorder, amongst multiple SNVs which are mostly missense VUS or B/LB.

Pan et al., 2024 (PMID: 38479391) reported 14 individuals with heterozygous variant in FRYL who presented with DD/ID, dysmorphic features, and other congenital anomalies in multiple systems. Except for DD/ID which was the only universal feature, observed phenotypes were variable and nonspecific.

Variants were confirmed de novo in all except one individual (duo testing excluded paternal inheritance although it was present at low frequency in gnomAD). Variant types include missense (5), fs/stop-gain (8) and canonical splice (1). Modelling 4/5 patient missense variants using flies showed that only one serves as a severe LoF variant, two others behave as partial LoF variants, and one variant had no functional impact (only variant not confirmed as de novo indicating this is a VUS). Four individuals also had P/LP variants in other genes (SF3B4, DHCR7, SLC6A19, SDHA) which could at least partially explain their phenotypes, and a further four harboured additional VUSs.
Sources: Literature
RASopathies v1.81 RRAS Sarah Leigh Classified gene: RRAS as Green List (high evidence)
RASopathies v1.81 RRAS Sarah Leigh Gene: rras has been classified as Green List (High Evidence).
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green was removed from gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Fetal anomalies v3.151 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Tag Q2_24_promote_green tag was added to gene: RRAS.
RASopathies v1.80 RRAS Sarah Leigh Publications for gene: RRAS were set to 24705357
RASopathies v1.79 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Fetal anomalies v3.151 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735
Cytopenia - NOT Fanconi anaemia v3.31 RRAS Sarah Leigh Publications for gene: RRAS were set to 34935735
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh commented on gene: RRAS: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.
RASopathies v1.79 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
RASopathies v1.79 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Noonan syndrome to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.151 RRAS Sarah Leigh Added comment: Comment on phenotypes: Phenotype from Gen2Phen
Fetal anomalies v3.151 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from ATYPICAL NOONAN SYNDROME to RRAS-related atypical Noonan syndrome
Fetal anomalies v3.150 RRAS Sarah Leigh Publications for gene: RRAS were set to
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh edited their review of gene: RRAS: Added comment: RRAS variants have not associated with a phenotype in OMIM or MONDO, but Gen2Phen lists a strong association between RRAS variants and RRAS-related atypical Noonan syndrome. Three germline RRAS variants have been reported (PMID: 24705357; 32815881; 34935735), associated with a RASopathy, which includes myelodysplastic syndrome and contributes to leukaemogenesis.; Changed rating: GREEN; Changed publications to: 24705357, 32815881, 34935735; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Added comment: Comment on phenotypes: RRAS-related atypical Noonan syndrome phenotype from Gen2Phen
Cytopenia - NOT Fanconi anaemia v3.30 RRAS Sarah Leigh Phenotypes for gene: RRAS were changed from Pediatric Myelodysplastic Syndrome to RRAS-related atypical Noonan syndrome
Cytopenia - NOT Fanconi anaemia v3.29 RRAS Sarah Leigh Publications for gene: RRAS were set to PMID: 34935735
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Classified gene: RRAS as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.28 RRAS Sarah Leigh Gene: rras has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh commented on gene: NAA60: NAA60 should be green on the Hereditary ataxia with onset in adulthood as four of the families described in table 1 (PMID: 38480682), also displayed either cerebellar syndrome (which often includes ataxia) or cerebellar ataxia (personal communication from Helen Brittain (Genomics England Clinical Fellow).
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC); signs of Parkinsonian presentation was evident in three families reported. Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Tag Q2_24_MOI tag was added to gene: NAA60.
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Hereditary ataxia with onset in adulthood v4.31 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Hereditary ataxia with onset in adulthood. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh Entity copied from White matter disorders and cerebral calcification - narrow panel v3.35
Adult onset neurodegenerative disorder v4.47 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to Adult onset neurodegenerative disorder. Sources: Literature,Expert Review Amber
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Mode of inheritance for gene: NAA60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.30 BTD Achchuthan Shanmugasundram Phenotypes for gene: BTD were changed from Biotinidase deficiency, OMIM:253260 to Biotinidase deficiency, OMIM:253260; optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram edited their review of gene: BTD: Changed phenotypes to: Biotinidase deficiency, OMIM:253260, optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Classified gene: BTD as Amber List (moderate evidence)
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Gene: btd has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: BTD.
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram gene: BTD was added
gene: BTD was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 26203071; 29025919; 32235217; 33364171
Phenotypes for gene: BTD were set to Biotinidase deficiency, OMIM:253260
Review for gene: BTD was set to GREEN
Added comment: PMID:26203071 - A 22-year-old man presented with a disabling extensive myelopathy and bilateral optic neuropathy which mimicked the findings of a (seronegative) neuromyelitis optica. A novel homozygous BTD variant (p.Ala439Asp) and a known variant (c.1413T>C/ p.Cys471Cys) were identified in this patient.

PMID:29025919 - Two unrelated individuals with adult-onset biotinidase deficiency had severe, but reversible optic neuropathy. They were identified with compound heterozygous variants (patient 1: p.Phe232Cys/ p.Leu440Pro; patient 2: p.Gln456His/ p.Arg538Cys).

PMID:32235217 - A 49-year-old man was reported with progressive optic atrophy, peripheral neuropathy, and systemic weakness and fatigue due to biotinidase deficiency. This patient was reported with compound heterozygous variants (p.Ala171Thr/ p.Asp444His)

PMID:33364171 - Two adult brothers were reported with biallelic BTD variants. Both of them presented with lower limb neuropathy and one had progressive optic neuropathy.
Sources: Literature
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Classified gene: SLIRP as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with compound heterozygous SLIRP variants and the gene should be rated red.
Possible mitochondrial disorder - nuclear genes v3.105 SLIRP Achchuthan Shanmugasundram Gene: slirp has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.104 SLIRP Achchuthan Shanmugasundram reviewed gene: SLIRP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: COL5A1.
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Classified gene: COL5A1 as Amber List (moderate evidence)
Cerebral vascular malformations v3.15 COL5A1 Achchuthan Shanmugasundram Gene: col5a1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.14 COL5A1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of heterozygous COL5A1 variants with this panel. However, there are only two cases reported with compound heterozygous variants. Hence the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Cerebral vascular malformations v3.14 COL5A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL5A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.13 COL5A1 Achchuthan Shanmugasundram Phenotypes for gene: COL5A1 were changed from Fibromuscular dysplasia, multifocal to Ehlers-Danlos syndrome, classic type, 1, OMIM:130000; Fibromuscular dysplasia, multifocal, OMIM:619329
Cerebral vascular malformations v3.12 COL5A1 Achchuthan Shanmugasundram Publications for gene: COL5A1 were set to PMID: 32938213
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram edited their review of gene: COL5A1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram edited their review of gene: COL5A1: Changed phenotypes to: Ehlers-Danlos syndrome, classic type, 1, OMIM:130000, Fibromuscular dysplasia, multifocal, OMIM:619329
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram changed review comment from: PMID:17053184 - Of 15 patients from seven families with spontaneous cervical artery dissections (CAD) recruited in this study, two patients from a family carried a rare variant in COL5A1 (p.Asp192Asn). One of them also carried a rare variant in COL5A2.

PMID:31903434 - Among 43 patients with cervical artery dissection (CeAD) analysed in this study, one patient had classic Ehlers Danlos syndrome due to two different missense variants in COL5A1 (p.Arg65Trp and p.Val172Phe), while another patient had missense variants in COL5A2 (p.Pro1103Leu) and COL5A1 (p.Thr1757Met).

PMID:32938213 - Four unrelated individuals were reported with the same heterozygous variant in COL5A1 (p.Gly514Ser) and they presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. The existence of a common haplotype among all four probands suggest founder effect.

PMID:33189937 - A 22-year-old patient with intracranial aneurysm and mild connective tissue manifestations reminiscent of EDS was identified with two COL5A1 missense variants in trans configuration (p.Gly530Ser and p.Pro1379Ser).

PMID:35911880; to: PMID:17053184 - Of 15 patients from seven families with spontaneous cervical artery dissections (CAD) recruited in this study, two patients from a family carried a rare variant in COL5A1 (p.Asp192Asn). One of them also carried a rare variant in COL5A2.

PMID:31903434 - Among 43 patients with cervical artery dissection (CeAD) analysed in this study, one patient had classic Ehlers Danlos syndrome due to two different missense variants in COL5A1 (p.Arg65Trp and p.Val172Phe), while another patient had missense variants in COL5A2 (p.Pro1103Leu) and COL5A1 (p.Thr1757Met).

PMID:32938213 - Four unrelated individuals were reported with the same heterozygous variant in COL5A1 (p.Gly514Ser) and they presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. The existence of a common haplotype among all four probands suggest founder effect.

PMID:33189937 - A 22-year-old patient with intracranial aneurysm and mild connective tissue manifestations reminiscent of EDS was identified with two COL5A1 missense variants in trans configuration (p.Gly530Ser and p.Pro1379Ser).

PMID:35911880 - A female was reported with postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction. She was identified with a heterozygous COL5A1 gene variant (p.Asp1648Gly).

This gene has been associated with relevant phenotypes in OMIM and Gene2Phenotype.
Cerebral vascular malformations v3.11 COL5A1 Achchuthan Shanmugasundram reviewed gene: COL5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 17053184, 31903434, 32938213, 33189937, 35911880; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram commented on gene: GRAP: As reviewed by Barbara Vona, two unrelated families were reported with the same homozygous missense variant. There is some functional data available as well.

This gene has been associated with relevant phenotype in OMIM (MIM #618456).
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Classified gene: GRAP as Red List (low evidence)
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Gene: grap has been classified as Red List (Low Evidence).
Monogenic hearing loss v4.35 GRAP Achchuthan Shanmugasundram Phenotypes for gene: GRAP were changed from Non-syndromic hearing loss to Deafness, autosomal recessive 114, OMIM:618456
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram reviewed gene: GRAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 114, OMIM:618456; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram Publications for gene: GRAP were set to PMID: 30610177
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram commented on gene: RCAN1: As reviewed by Zornitza Stark, whole-genome sequencing performed on 320 individuals from 201 families with familial and sporadic nephrotic syndrome (NS)/ focal segmental glomerulosclerosis (FSGS) identified two variants in RCAN1 gene in two families with autosomal dominant FSGS/ steroid-resistant nephrotic syndrome (SRNS). In addition, there is some functional data available.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.

This gene can be rated amber with current evidence.
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Classified gene: RCAN1 as Amber List (moderate evidence)
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.11 RCAN1 Achchuthan Shanmugasundram Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to focal segmental glomerulosclerosis, MONDO:0100313; nephrotic syndrome, MONDO:0005377
Proteinuric renal disease v4.10 RCAN1 Achchuthan Shanmugasundram reviewed gene: RCAN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: focal segmental glomerulosclerosis, MONDO:0100313, nephrotic syndrome, MONDO:0005377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Classified gene: PRDM15 as Amber List (moderate evidence)
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated individuals with three different biallelic variants, mouse and Xenopus models and functional data) for the promotion of this gene to green rating in the next GMS update.
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.9 PRDM15 Achchuthan Shanmugasundram Phenotypes for gene: PRDM15 were changed from Steroid resistant nephrotic syndrome; Holoprosencephaly to steroid-resistant nephrotic syndrome, MONDO:0044765
Proteinuric renal disease v4.8 PRDM15 Achchuthan Shanmugasundram Publications for gene: PRDM15 were set to 31950080
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PRDM15.
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33593823; Phenotypes: steroid-resistant nephrotic syndrome, MONDO:0044765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Classified gene: PDXK as Amber List (moderate evidence)
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PDXK.
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Classified gene: PDXK as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Gene: pdxk has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.86 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PDXK.
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v3.86 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Fetal anomalies v3.149 NRXN2 Sarah Leigh Publications for gene: NRXN2 were set to
Fetal hydrops v1.64 FZD6 Irina Adamena gene: FZD6 was added
gene: FZD6 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: FZD6 was set to Unknown
Publications for gene: FZD6 were set to PMID: 33082562
Phenotypes for gene: FZD6 were set to Nonimmune hydrops fetalis
Review for gene: FZD6 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 GLMN Irina Adamena gene: GLMN was added
gene: GLMN was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: GLMN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLMN were set to PMID: 33082562
Phenotypes for gene: GLMN were set to Nonimmune hydrops fetalis
Review for gene: GLMN was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 ITGA9 Irina Adamena gene: ITGA9 was added
gene: ITGA9 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: ITGA9 was set to Unknown
Publications for gene: ITGA9 were set to PMID: 33082562
Phenotypes for gene: ITGA9 were set to Nonimmune hydrops fetalis
Review for gene: ITGA9 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Hereditary neuropathy or pain disorder v3.84 SPG7 Sarah Leigh changed review comment from: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; to: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Kirsty Williams), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).
Fetal hydrops v1.64 CANT1 Irina Adamena gene: CANT1 was added
gene: CANT1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: CANT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CANT1 were set to PMID: 33082562
Phenotypes for gene: CANT1 were set to Nonimmune hydrops fetalis
Review for gene: CANT1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 PTH1R Irina Adamena reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GPI Irina Adamena gene: GPI was added
gene: GPI was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: GPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPI were set to PMID: 33082562
Phenotypes for gene: GPI were set to Nonimmune hydrops fetalis
Review for gene: GPI was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 G6PD Irina Adamena gene: G6PD was added
gene: G6PD was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: G6PD 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: G6PD were set to PMID: 33082562
Phenotypes for gene: G6PD were set to Nonimmune hydrops fetalis
Review for gene: G6PD was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 RPL15 Irina Adamena gene: RPL15 was added
gene: RPL15 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: RPL15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL15 were set to PMID: 33082562
Phenotypes for gene: RPL15 were set to Nonimmune hydrops fetalis
Review for gene: RPL15 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 PRF1 Irina Adamena gene: PRF1 was added
gene: PRF1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRF1 were set to PMID: 33082562
Phenotypes for gene: PRF1 were set to Nonimmune hydrops fetalis
Review for gene: PRF1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 GATA1 Irina Adamena reviewed gene: GATA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal hydrops v1.64 SEC23B Irina Adamena gene: SEC23B was added
gene: SEC23B was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SEC23B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC23B were set to PMID: 33082562
Phenotypes for gene: SEC23B were set to Nonimmune hydrops fetalis
Review for gene: SEC23B was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 CDAN1 Irina Adamena reviewed gene: CDAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SPTB Irina Adamena gene: SPTB was added
gene: SPTB was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SPTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTB were set to PMID: 33082562
Phenotypes for gene: SPTB were set to Nonimmune hydrops fetalis
Review for gene: SPTB was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC4A1 Irina Adamena gene: SLC4A1 was added
gene: SLC4A1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SLC4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC4A1 were set to PMID: 33082562
Phenotypes for gene: SLC4A1 were set to Nonimmune hydrops fetalis
Review for gene: SLC4A1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Congenital muscular dystrophy v4.23 FHL1 Sarah Leigh changed review comment from: In response to Zornitza Starks' review, are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?; to: In response to Zornitza Starks' review, Helen Brittain (Genomics England Clinical Fellow) was asked the following question: are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)?
Helen Brittain replied that in PMID: 19181672, the patients present with weakness and a raised CK - this would make clinicians think of a muscular dystrophy primarily. Although technically it may be a myopathy, I think it is enough of a mimic to be included on both the dystrophy and myopathy panels. Therefore this gene should remain green on Congenital muscular dystrophy
Fetal hydrops v1.64 SGPL1 Irina Adamena reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GBE1 Irina Adamena reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 MT-TL1 Irina Adamena gene: MT-TL1 was added
gene: MT-TL1 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to PMID: 33082562
Phenotypes for gene: MT-TL1 were set to Nonimmune hydrops fetalis
Review for gene: MT-TL1 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MT-TE Irina Adamena gene: MT-TE was added
gene: MT-TE was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL
Publications for gene: MT-TE were set to PMID: 33082562
Phenotypes for gene: MT-TE were set to Nonimmune hydrops fetalis
Review for gene: MT-TE was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MVK Irina Adamena reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 MGAT2 Irina Adamena gene: MGAT2 was added
gene: MGAT2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: MGAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MGAT2 were set to PMID: 33082562
Phenotypes for gene: MGAT2 were set to Nonimmune hydrops fetalis
Review for gene: MGAT2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC17A5 Irina Adamena reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GLB1 Irina Adamena reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GUSB Irina Adamena reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 GALNS Irina Adamena reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33082562; Phenotypes: Nonimmune hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SCN5A Irina Adamena gene: SCN5A was added
gene: SCN5A was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: SCN5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN5A were set to PMID: 33082562
Phenotypes for gene: SCN5A were set to Nonimmune hydrops fetalis
Review for gene: SCN5A was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 KCNH2 Irina Adamena gene: KCNH2 was added
gene: KCNH2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: KCNH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH2 were set to PMID: 33082562
Phenotypes for gene: KCNH2 were set to Nonimmune hydrops fetalis
Review for gene: KCNH2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 ALPK3 Irina Adamena gene: ALPK3 was added
gene: ALPK3 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: ALPK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALPK3 were set to PMID: 33082562
Phenotypes for gene: ALPK3 were set to Nonimmune hydrops fetalis
Review for gene: ALPK3 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 MYH7 Irina Adamena gene: MYH7 was added
gene: MYH7 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7 were set to PMID: 33082562
Phenotypes for gene: MYH7 were set to Nonimmune hydrops fetalis
Review for gene: MYH7 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 LAMB2 Irina Adamena gene: LAMB2 was added
gene: LAMB2 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB2 were set to PMID: 33082562
Phenotypes for gene: LAMB2 were set to Nonimmune hydrops fetalis
Review for gene: LAMB2 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Classified gene: NAA60 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
White matter disorders and cerebral calcification - narrow panel v3.34 NAA60 Sarah Leigh Gene: naa60 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v3.33 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Review for gene: NAA60 was set to GREEN
Added comment: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
Fetal hydrops v1.64 CDC42 Irina Adamena gene: CDC42 was added
gene: CDC42 was added to Fetal hydrops. Sources: Literature
Mode of inheritance for gene: CDC42 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42 were set to PMID: 33082562
Phenotypes for gene: CDC42 were set to Nonimmune hydrops fetalis
Review for gene: CDC42 was set to GREEN
Added comment: Gene with strong evidence for fetal hydrops (PMID: 33082562)
Sources: Literature
Fetal hydrops v1.64 SLC30A5 Irina Adamena changed review comment from: Four affected children with homozygous loss of function variants in SLC30A5 gene with cardiomyopathy, hydrops fetalis, or cystic hygroma.; to: Four affected children with homozygous loss of function variants in SLC30A5 gene with cardiomyopathy, hydrops fetalis, or cystic hygroma (PMID: 33547425).
Fetal hydrops v1.64 ANGPT2 Irina Adamena reviewed gene: ANGPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34876502; Phenotypes: Hydrops fetalis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops v1.64 SLC30A5 Irina Adamena reviewed gene: SLC30A5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33547425; Phenotypes: hydrops fetalis, cardiomyopathy, cystic hygroma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Classified gene: NLRP12 as Amber List (moderate evidence)
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of NLRP12 with sensorineural hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Gene: nlrp12 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: NLRP12.
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram changed review comment from: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature; to: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.

NLRP12 has been associated with Familial cold autoinflammatory syndrome 2 (MIM #611762) in OMIM and sensorineural deafness has been listed as one of the clinical presentations of this phenotype.

Sources: Literature
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram gene: NLRP12 was added
gene: NLRP12 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP12 were set to 18230725; 24064030; 31820221
Phenotypes for gene: NLRP12 were set to Familial cold autoinflammatory syndrome 2, OMIM:611762; sensorineural hearing loss disorder, MONDO:0020678
Review for gene: NLRP12 was set to GREEN
Added comment: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Classified gene: KDM3B as Amber List (moderate evidence)
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are four cases reported with KDM3B variants and with cancer, of which three cases are childhood solid tumours (two cases with Wilms tumour and one case with Hodgkin lymphoma), while the fourth case had acute myeloid leukaemia in childhood.

Hence, this gene can be promoted to green rating in the next GMS review.
Childhood solid tumours v4.18 KDM3B Achchuthan Shanmugasundram Gene: kdm3b has been classified as Amber List (Moderate Evidence).
Childhood solid tumours v4.17 KDM3B Achchuthan Shanmugasundram Phenotypes for gene: KDM3B were changed from Diets-Jongmans syndrome to Diets-Jongmans syndrome, OMIM:618846
Childhood solid tumours v4.16 KDM3B Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KDM3B.
Childhood solid tumours v4.16 KDM3B Achchuthan Shanmugasundram reviewed gene: KDM3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 30929739; Phenotypes: Diets-Jongmans syndrome, OMIM:618846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.521 DENND5B Sarah Leigh Classified gene: DENND5B as Amber List (moderate evidence)
Intellectual disability v5.521 DENND5B Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.521 DENND5B Sarah Leigh Gene: dennd5b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.520 DENND5B Sarah Leigh Tag Q2_24_promote_green tag was added to gene: DENND5B.
Tag Q2_24_NHS_review tag was added to gene: DENND5B.
Early onset or syndromic epilepsy v4.193 DENND5B Sarah Leigh Classified gene: DENND5B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.193 DENND5B Sarah Leigh Gene: dennd5b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.192 DENND5B Sarah Leigh edited their review of gene: DENND5B: Changed rating: AMBER
Early onset or syndromic epilepsy v4.192 DENND5B Sarah Leigh gene: DENND5B was added
gene: DENND5B was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DENND5B were set to 38387458
Phenotypes for gene: DENND5B were set to DENND5B associated neurodevelopmental disorder
Review for gene: DENND5B was set to GREEN
Added comment: DENND5B variants have not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38387458 reports five de novo missense variants in five unrelated cases. The carriers of these DENND5B variants have a neurodevelopmental disorder, which is characterized by psychomotor delay (5/5 cases), intellectual disability, ranging from severe to mild (3/5 cases, although one of the negative cases was a 2 year old child, who was considered to be too young to make the assessment, although the DD/intellectual disability phenotype was considered to be moderate in this case), epilepsy (2/5 cases) and hypotonia (4/5 cases). The authors of PMID: 38387458 also report the functional effects of the DENND5B variants, which revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. They conclude that this effect is likely to be caused by the predicted disruption of protein folding in the variant DENND5B peptide.
Sources: Literature
Intellectual disability v5.520 DENND5B Sarah Leigh gene: DENND5B was added
gene: DENND5B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DENND5B were set to 38387458
Phenotypes for gene: DENND5B were set to DENND5B associated neurodevelopmental disorder
Review for gene: DENND5B was set to GREEN
Added comment: DENND5B variants have not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38387458 reports five de novo missense variants in five unrelated cases. The carriers of these DENND5B variants have a neurodevelopmental disorder, which is characterized by psychomotor delay (5/5 cases), intellectual disability, ranging from severe to mild (3/5 cases, although one of the negative cases was a 2 year old child, who was considered to be too young to make the assessment, although the DD/intellectual disability phenotype was considered to be moderate in this case), epilepsy (2/5 cases) and hypotonia (4/5 cases). The authors of PMID: 38387458 also report the functional effects of the DENND5B variants, which revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. They conclude that this effect is likely to be caused by the predicted disruption of protein folding in the variant DENND5B peptide.
Sources: Literature
Intellectual disability v5.519 TBC1D2B Sarah Leigh Tag watchlist was removed from gene: TBC1D2B.
Tag Q2_24_promote_green tag was added to gene: TBC1D2B.
Tag Q2_24_NHS_review tag was added to gene: TBC1D2B.
Intellectual disability v5.519 TBC1D2B Sarah Leigh Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability v5.519 TBC1D2B Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.519 TBC1D2B Sarah Leigh Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.518 TBC1D2B Sarah Leigh reviewed gene: TBC1D2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v4.191 TBC1D2B Sarah Leigh edited their review of gene: TBC1D2B: Added comment: TBC1D2B variants have been associated with Neurodevelopmental disorder with seizures and gingival overgrowth (OMIM:619323) and as definitive Gen2Phen gene for TBC1D2B-related neurodevelopmental disorder. So far, 11 TBC1D2B variants have been reported in 8 unrelated families. Global developmental delay (HP:0001263) was reported in 5/8 families, mental deterioration (HP:0001268) was seen in 5/8 families and seizures (HP:0001250) were reported in 8/8 families (four of these were controlled with medication)(PMID: 38374468).; Changed rating: GREEN
Intellectual disability v5.518 TBC1D2B Sarah Leigh Publications for gene: TBC1D2B were set to 32623794
Early onset or syndromic epilepsy v4.191 TBC1D2B Sarah Leigh Publications for gene: TBC1D2B were set to 32623794
Intellectual disability v5.517 TBC1D2B Sarah Leigh Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323; neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148
Early onset or syndromic epilepsy v4.190 TBC1D2B Sarah Leigh Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323; neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148
Ichthyosis and erythrokeratoderma v3.28 DBR1 Achchuthan Shanmugasundram Classified gene: DBR1 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.28 DBR1 Achchuthan Shanmugasundram Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: DBR1.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant.; to: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant. There is functional data available. This gene can only be rated amber with the current evidence.

The 'founder-effect' tag is added to this gene.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Classified gene: DBR1 as No list
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant.
Ichthyosis and erythrokeratoderma v3.27 DBR1 Achchuthan Shanmugasundram Gene: dbr1 has been removed from the panel.
Ichthyosis and erythrokeratoderma v3.26 DBR1 Achchuthan Shanmugasundram edited their review of gene: DBR1: Changed phenotypes to: ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v3.26 DBR1 Achchuthan Shanmugasundram Phenotypes for gene: DBR1 were changed from Ichthyosis (MONDO#0019269), DBR1-related to ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v3.25 DBR1 Achchuthan Shanmugasundram reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inherited ichthyosis, MONDO:0015947; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Classified gene: ADAMTSL2 as Amber List (moderate evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, six families were reported with the same monoallelic variant and with Ehlers-Danlos syndrome. However, there is no functional data and it is not clear whether it is a founder variant. Hence, this gene can only be rated amber with the current evidence in this panel.
Ehlers Danlos syndrome with a likely monogenic cause v3.12 ADAMTSL2 Achchuthan Shanmugasundram Gene: adamtsl2 has been classified as Amber List (Moderate Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v3.11 ADAMTSL2 Achchuthan Shanmugasundram reviewed gene: ADAMTSL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, MONDO:0020066; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital adrenal hypoplasia v3.11 KDM1A Achchuthan Shanmugasundram Phenotypes for gene: KDM1A were changed from Food-dependent Cushing syndrome (FDCS) to Cleft palate, psychomotor retardation, and distinctive facial features, OMIM:616728; congenital adrenal hyperplasia, MONDO:0018479
Congenital adrenal hypoplasia v3.10 KDM1A Achchuthan Shanmugasundram Classified gene: KDM1A as Red List (low evidence)
Congenital adrenal hypoplasia v3.10 KDM1A Achchuthan Shanmugasundram Gene: kdm1a has been classified as Red List (Low Evidence).
Congenital adrenal hypoplasia v3.9 KDM1A Achchuthan Shanmugasundram reviewed gene: KDM1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features, OMIM:616728, congenital adrenal hyperplasia, MONDO:0018479; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Classified gene: GNB1 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are five cases reported with cutaneous mastocytosis.

Cutaneous mastocytosis has also been reported as one of the clinical presentations of the OMIM phenotype Intellectual developmental disorder, autosomal dominant 42 (MIM #616973).

Hence, this gene can be promoted to green rating in the next GMS review.
Rare genetic inflammatory skin disorders v3.10 GNB1 Achchuthan Shanmugasundram Gene: gnb1 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v3.9 GNB1 Achchuthan Shanmugasundram Phenotypes for gene: GNB1 were changed from Cutaneous mastocytosis; Intellectual developmental disorder, autosomal dominant 42 to Intellectual developmental disorder, autosomal dominant 42, OMIM:616973; cutaneous mastocytosis, MONDO:0019023
Rare genetic inflammatory skin disorders v3.8 GNB1 Achchuthan Shanmugasundram Publications for gene: GNB1 were set to 35119134
Rare genetic inflammatory skin disorders v3.7 GNB1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GNB1.
Rare genetic inflammatory skin disorders v3.7 GNB1 Achchuthan Shanmugasundram reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29174093, 30194818, 35119134; Phenotypes: Intellectual developmental disorder, autosomal dominant 42, OMIM:616973, cutaneous mastocytosis, MONDO:0019023; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Tag Q2_24_NHS_review tag was added to gene: SECISBP2.
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Classified gene: SECISBP2 as Amber List (moderate evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases and animal models) for the promotion of this gene to green rating in the next GMS review.
Thoracic aortic aneurysm or dissection (GMS) v3.11 SECISBP2 Achchuthan Shanmugasundram Gene: secisbp2 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.10 SECISBP2 Achchuthan Shanmugasundram Phenotypes for gene: SECISBP2 were changed from Growth retardation; sensorineural hearing loss; muscular dystrophy; thoracic aortic aneurysm; raised circulating thyroxine and low plasma selenium to Thyroid hormone metabolism, abnormal, 1, OMIM:609698; thoracic aortic aneurysm
Thoracic aortic aneurysm or dissection (GMS) v3.9 SECISBP2 Achchuthan Shanmugasundram Publications for gene: SECISBP2 were set to PMID 38042913; PMID 21084748
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: SECISBP2.
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 Achchuthan Shanmugasundram reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38042913; Phenotypes: Thyroid hormone metabolism, abnormal, 1, OMIM:609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.83 RP1L1 Arina Puzriakova Added comment: Comment on mode of inheritance: This gene is associated with occult macular dystrophy (monoallelic variants) and retinitis pigmentosa (biallelic variants) (https://omim.org/entry/608581) with sufficient cases reported for each phenotype. Currently the monoallelic phenotype is not represented on any GMS panels.

Following curation and consultation with the Genomics England clinical team, there was agreement that macular dystrophy is part of the phenotypic target for this panel. Based on previous reviews, it is not clear why the monoallelic MOI was overwritten and therefore this gene will be flagged for specialist review to determine whether the MOI should stay as 'biallelic' or be updated to 'both mono- and biallelic'.
Retinal disorders v4.83 RP1L1 Arina Puzriakova Mode of inheritance for gene: RP1L1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.82 RP1L1 Arina Puzriakova Tag Q2_24_MOI tag was added to gene: RP1L1.
Tag Q2_24_expert_review tag was added to gene: RP1L1.
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from ?Deafness, autosomal recessive 104 , OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Classified gene: RIPOR2 as Amber List (moderate evidence)
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Only one variant was reported with both monoallelic and biallelic inheritance. There is some functional data for both modes of inheritance. Although there are 12 unrelated cases reported with the same monoallelic variant, this variant was suggested to be founder variant. Hence, this gene can only be rated amber with the current evidence for both modes of inheritance.
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram changed review comment from: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.; to: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect. Hence, the 'founder-effect' tag was added.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram edited their review of gene: RIPOR2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24958875, 32631815; Phenotypes: Deafness, autosomal dominant 21, OMIM:607017, ?Deafness, autosomal recessive 104, OMIM:616515; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.515 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Intellectual disability v5.515 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
DDG2P v3.86 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
DDG2P v3.86 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Congenital myopathy v4.37 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Congenital myopathy v4.37 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from congenital myopathy, MONDO:0019952 to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Intellectual disability v5.514 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
DDG2P v3.85 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
Congenital myopathy v4.36 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
Renal ciliopathies v3.5 DLG5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Yuksel-Vogel-Bauser syndrome, OMIM:620703)
Renal ciliopathies v3.5 DLG5 Arina Puzriakova Phenotypes for gene: DLG5 were changed from DLG5-associated developmental disorder (monoallelic); DLG5-associated developmental disorder (biallelic) to Yuksel-Vogel-Bauser syndrome, OMIM:620703
Unexplained young onset end-stage renal disease v3.40 DLG5 Arina Puzriakova Phenotypes for gene: DLG5 were changed from DLG5-associated developmental disorder (monoallelic); DLG5-associated developmental disorder (biallelic) to Yuksel-Vogel-Bauser syndrome, OMIM:620703
Renal ciliopathies v3.4 DLG5 Arina Puzriakova Tag gene-checked was removed from gene: DLG5.
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747)
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747
Parkinson Disease and Complex Parkinsonism v1.121 PTRHD1 Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747
Intellectual disability v5.513 PTRHD1 Arina Puzriakova Tag gene-checked was removed from gene: PTRHD1.
DDG2P v3.85 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
DDG2P v3.85 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Structural eye disease v3.76 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Structural eye disease v3.76 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Coloboma, None to Microphthalmia/coloboma 11, OMIM:620731
Fetal anomalies v3.147 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Fetal anomalies v3.147 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Ocular coloboma v1.47 FZD5 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Microphthalmia/coloboma 11, OMIM:620731)
Ocular coloboma v1.47 FZD5 Arina Puzriakova Phenotypes for gene: FZD5 were changed from Coloboma to Microphthalmia/coloboma 11, OMIM:620731
Structural eye disease v3.75 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
DDG2P v3.84 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
Ocular coloboma v1.46 FZD5 Arina Puzriakova Tag gene-checked was removed from gene: FZD5.
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774)
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062 to Developmental and epileptic encephalopathy 114, OMIM:620774
Early onset or syndromic epilepsy v4.188 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has relevant phenotypes listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774 and Generalized epilepsy with febrile seizures plus, type 12, OMIM:620755)
Early onset or syndromic epilepsy v4.188 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062; generalized epilepsy with febrile seizures plus, MONDO:0018214 to Developmental and epileptic encephalopathy 114, OMIM:620774; Generalized epilepsy with febrile seizures plus, type 12, OMIM:620755
DDG2P v3.84 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774)
DDG2P v3.84 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from SLC32A1-associated developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 114, OMIM:620774
Intellectual disability v5.512 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
Early onset or syndromic epilepsy v4.187 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
DDG2P v3.83 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
DDG2P v3.83 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
DDG2P v3.83 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from CORNELIA DE LANGE-LIKE SYNDROME to Cornelia de Lange syndrome 6, OMIM:620568
Severe microcephaly v4.67 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, OMIM:620568
Intellectual disability v5.512 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
Intellectual disability v5.512 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face to Cornelia de Lange syndrome 6, OMIM:620568
DDG2P v3.82 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v5.511 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v5.511 CAPRIN1 Arina Puzriakova Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Early onset or syndromic epilepsy v4.187 CAPRIN1 Arina Puzriakova Publications for gene: CAPRIN1 were set to 35979925
DDG2P v3.82 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
DDG2P v3.82 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Early onset or syndromic epilepsy v4.186 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
Early onset or syndromic epilepsy v4.186 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behavior; Seizures to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Intellectual disability v5.509 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
Early onset or syndromic epilepsy v4.185 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
DDG2P v3.81 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from AUTISM OR INTELLECTUAL DISABILITY to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
DDG2P v3.80 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
Ataxia and cerebellar anomalies - narrow panel v4.59 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Cerebellar ataxia, MONDO:0000437; Early-onset ataxia to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
DDG2P v3.80 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
DDG2P v3.80 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from WNK3-related neurodevelopmental disorder to WNK3-related neurodevelopmental disorder; Prieto syndrome, OMIM:309610
Early onset or syndromic epilepsy v4.185 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Intellectual disability v5.509 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Early onset or syndromic epilepsy v4.185 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Intellectual disability v5.508 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Malformations of cortical development v4.26 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from Intellectual disability, MONDO:0001071 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Malformations of cortical development v4.25 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Intellectual disability v5.508 C12orf4 Arina Puzriakova Phenotypes for gene: C12orf4 were changed from Autosomal recessive intellectual disability to Intellectual developmental disorder, autosomal recessive 66, OMIM:618221
Intellectual disability v5.507 C12orf4 Arina Puzriakova commented on gene: C12orf4
Intellectual disability v5.507 C12orf4 Arina Puzriakova Tag new-gene-name tag was added to gene: C12orf4.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: MVD.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Classified gene: MVD as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Added comment: Comment on list classification: At least 5 individuals reported (PMID: 30942823; 33491095) which meets the criteria for classifying this gene-disease association as Green at the next GMS panel update.
Mosaic skin disorders - deep sequencing v2.47 MVD Arina Puzriakova Gene: mvd has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v2.46 MVD Arina Puzriakova commented on gene: MVD
Mosaic skin disorders - deep sequencing v2.46 MVD Arina Puzriakova Publications for gene: MVD were set to 30942823
Mosaic skin disorders - deep sequencing v2.45 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from Linear porokeratosis to Porokeratosis 7, multiple types, OMIM:614714
Rare genetic inflammatory skin disorders v3.7 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from POROKERATOSIS 7, MULTIPLE TYPES, OMIM:614714 to Porokeratosis 7, multiple types, OMIM:614714
Familial disseminated superficial actinic porokeratosis v1.3 MVD Arina Puzriakova Phenotypes for gene: MVD were changed from Porokeratosis 7, multiple types, 614714; actinic/non-actinic disseminated superficial porokeratosis; POROK7; DSAP/DSP to Porokeratosis 7, multiple types, OMIM:614714
Skeletal dysplasia v4.55 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti 308300; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Primary lymphoedema v3.11 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency 300301 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Intellectual disability v5.507 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, type II, 308300Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301Immunodeficiency, isolated, 300584{Atypical mycobacteriosis, familial}, 300636Invasive pneumococcal disease, recurrent isolated, 2, 300640; INCONTINENTIA PIGMENTI (IP) to Incontinentia pigmenti, OMIM:308300
Incontinentia pigmenti v1.2 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, OMIM:308300
Structural eye disease v3.75 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, IP, 308300 to Incontinentia pigmenti, OMIM:308300
Retinal disorders v4.82 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Early onset or syndromic epilepsy v4.184 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova changed review comment from: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents the most likely diagnostic route for these cases and therefore a Green rating on this panel would be appropriate.; to: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents a plausible route for referral and diagnosis for these cases and therefore a Green rating on this panel would be appropriate.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.197 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Immunodeficiency 33, 300636; Ectodermal dysplasia, hypohidrotic, with immune deficiency 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Immunodeficiency, isolated, 300584; Invasive pneumococcal disease, recurrent isolated, 2,300640; Defects of TLR/NFkappa-B signalling; Anhidrotic ectodermal dysplasia (in some), various infections (bacteria, mycobacteria, viruses and fungi), colitis, conical teeth, variable defects of skin, hair and teeth, monocyte dysfunction; Combined immunodeficiencies with associated or syndromic features to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291; Immunodeficiency 33, OMIM:300636
Rare genetic inflammatory skin disorders v3.6 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti; Incontinentia pigmenti, Ectodermal dysplasia to Incontinentia pigmenti, OMIM:308300
Ectodermal dysplasia without a known gene mutation v1.28 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, type II, 308300; Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Immunodeficiency, isolated, 300584; {Atypical mycobacteriosis, familial}, 300636:Invasive pneumococcal disease, recurrent isolated, 2, 300640; Ectodermal Dysplasia, Hypohidrotic, With Immune Deficiency to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Ectodermal dysplasia v3.29 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal Dysplasia, Hypohidrotic, With Immune Deficiency; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; {Atypical mycobacteriosis, familial}, 300636:Invasive pneumococcal disease, recurrent isolated, 2, 300640; Immunodeficiency, isolated, 300584; Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291; Incontinentia pigmenti, type II, 308300 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Gastrointestinal epithelial barrier disorders v1.75 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Immunodeficiency 33, 300636; Immunodeficiency, isolated, 300584 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Infantile enterocolitis & monogenic inflammatory bowel disease v1.43 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal X-linked dysplasia, hypohidrotic, with immune deficiency 300291 to Ectodermal dysplasia and immunodeficiency 1, OMIM:300291
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Classified gene: IKBKG as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Added comment: Comment on list classification: Incontinentia pigmenti (IP) is a X-linked dominant disorder associated with variants in the IKBKG gene. IP is mostly lethal in males in utero, and only very rare surviving male cases have somatic mosaicism. Phenotypically, cutaneous lesions manifest in Blaschkoid distribution.

Overall 'R327 Mosaic skin disorders - deep sequencing' represents the most likely diagnostic route for these cases and therefore a Green rating on this panel would be appropriate.
Mosaic skin disorders - deep sequencing v2.44 IKBKG Arina Puzriakova Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v2.43 IKBKG Arina Puzriakova Tag somatic tag was added to gene: IKBKG.
Tag Q2_24_promote_green tag was added to gene: IKBKG.
Mosaic skin disorders - deep sequencing v2.43 IKBKG Arina Puzriakova Publications for gene: IKBKG were set to
Mosaic skin disorders - deep sequencing v2.42 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Ectodermal dysplasia and immunodeficiency 1, 300291; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301; Incontinentia pigmenti, 308300 to Incontinentia pigmenti, OMIM:308300
Retinal disorders v4.81 SAMD7 Arina Puzriakova commented on gene: SAMD7
Rare genetic inflammatory skin disorders v3.5 ADAMTS2 Dmitrijs Rots reviewed gene: ADAMTS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Thoracic aortic aneurysm or dissection (GMS) v3.8 SECISBP2 krishna chatterjee gene: SECISBP2 was added
gene: SECISBP2 was added to Thoracic aortic aneurysm or dissection (GMS). Sources: Literature
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to PMID 38042913; PMID 21084748
Phenotypes for gene: SECISBP2 were set to Growth retardation; sensorineural hearing loss; muscular dystrophy; thoracic aortic aneurysm; raised circulating thyroxine and low plasma selenium
Penetrance for gene: SECISBP2 were set to Complete
Review for gene: SECISBP2 was set to GREEN
Added comment: Biallelic defects in this gene cause a multi system disorder with deficiency of most human selenoproteins. Phenotypes listed here are associated with a biochemical signature of elevated circulating T4 (thyroxine) and low plasma selenium.

Since some pathogenic variants can be in non-coding regions and cryptic, we suggest a high index of suspicion even in cases of aortic aneurysm with an apparently monoallelic SECISBP2 defect. In such cases, we advocate measuring circulating T4 and selenium; if these biomarker levels are abnormal a cryptic mutation on the other allele should be sought.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.39 RTN2 Nour Elkhateeb reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38527963; Phenotypes: Weakness in the distal upper and lower limbs, Lower limb spasticity, Hyperreflexia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb changed review comment from: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.; to: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb changed review comment from: A recent publication has described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.; to: A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.
Hereditary spastic paraplegia v1.308 RTN2 Nour Elkhateeb reviewed gene: RTN2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38527963; Phenotypes: Weakness in the distal upper and lower limbs, Lower limb spasticity, Hyperreflexia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia v1.332 FGF14 Evan Reid reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMC10844931; Phenotypes: Adult onset cerebellar ataxia, adult onsent episodic ataxia, cerebellar oculomotor disturbances, vestibulopathy, peripheral neuropathy, dysautonomia, spasticity, parkinsonism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hydrocephalus v4.4 HYLS1 Arina Puzriakova Tag founder-effect tag was added to gene: HYLS1.
Intellectual disability v5.506 ZFX Tracy Lester reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: Intellectual disability, developmental delay, behavioural abnormalities, hypotonia, dysmorphic facies; 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 v5.506 CLEC16A Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CLEC16A.
Intellectual disability v5.506 GLI3 Tracy Lester reviewed gene: GLI3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v4.24 CLCN5 John Sayer gene: CLCN5 was added
gene: CLCN5 was added to Cystic kidney disease. Sources: Literature
Mode of inheritance for gene: CLCN5 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: CLCN5 were set to 7922301; 37641036
Phenotypes for gene: CLCN5 were set to cystic kdiney disease; cortical cysts; medullary cysts; nephrocalcinosis; low molecular weight proteinuria; hypercalciuria
Penetrance for gene: CLCN5 were set to Complete
Review for gene: CLCN5 was set to GREEN
Added comment: Oliver Wrong noted kidney cysts in 33% of his cohort and I think Dent disease is such a difficult diagnosis to make, adding it to the cystic panel will identify new cases presenting with mild cystic kidney disease
Sources: Literature
Monogenic short stature v0.168 ISCA-37429-Loss Arina Puzriakova Entity copied from Growth failure in early childhood v3.87
Monogenic short stature v0.168 ISCA-37429-Loss Arina Puzriakova Region: ISCA-37429-Loss was added
Region: ISCA-37429-Loss was added to Monogenic short stature. Sources: Expert Review Red,ClinGen
Mode of inheritance for Region: ISCA-37429-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37429-Loss were set to 20026556; 14630905
Phenotypes for Region: ISCA-37429-Loss were set to Wolf-Hirschhorn syndrome, OMIM:194190
Monogenic short stature v0.167 ISCA-37420-Loss Arina Puzriakova Entity copied from Growth failure in early childhood v3.87
Monogenic short stature v0.167 ISCA-37420-Loss Arina Puzriakova Region: ISCA-37420-Loss was added
Region: ISCA-37420-Loss was added to Monogenic short stature. Sources: Expert Review Red,ClinGen
Mode of inheritance for Region: ISCA-37420-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37420-Loss were set to 25217958; 18628315
Phenotypes for Region: ISCA-37420-Loss were set to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Monogenic short stature v0.166 ISCA-37406-Loss Arina Puzriakova Entity copied from Growth failure in early childhood v3.87
Monogenic short stature v0.166 ISCA-37406-Loss Arina Puzriakova Region: ISCA-37406-Loss was added
Region: ISCA-37406-Loss was added to Monogenic short stature. Sources: Expert Review Red,ClinGen
Mode of inheritance for Region: ISCA-37406-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37406-Loss were set to 16783566; 10573006
Phenotypes for Region: ISCA-37406-Loss were set to Chromosome 16p13.3 deletion syndrome, OMIM:610543
Monogenic short stature v0.165 ISCA-37397-Loss Arina Puzriakova Entity copied from Growth failure in early childhood v3.86
Monogenic short stature v0.165 ISCA-37397-Loss Arina Puzriakova Region: ISCA-37397-Loss was added
Region: ISCA-37397-Loss was added to Monogenic short stature. Sources: Expert Review Red,ClinGen
Mode of inheritance for Region: ISCA-37397-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37397-Loss were set to 18179902; 23765049; 21671380
Phenotypes for Region: ISCA-37397-Loss were set to Chromosome 22q11.2 deletion syndrome, distal, OMIM:611867
Monogenic short stature v0.164 ISCA-37392-Loss Arina Puzriakova Entity copied from Growth failure in early childhood v3.85
Monogenic short stature v0.164 ISCA-37392-Loss Arina Puzriakova Region: ISCA-37392-Loss was added
Region: ISCA-37392-Loss was added to Monogenic short stature. Sources: Expert Review Red,ClinGen
Mode of inheritance for Region: ISCA-37392-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37392-Loss were set to 20301427
Phenotypes for Region: ISCA-37392-Loss were set to Williams-Beuren syndrome, OMIM:194050
Monogenic short stature v0.163 ZPR1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.163 ZPR1 Arina Puzriakova gene: ZPR1 was added
gene: ZPR1 was added to Monogenic short stature. Sources: Literature,Expert Review Red
founder-effect tags were added to gene: ZPR1.
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to ?Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321
Monogenic short stature v0.162 XRCC4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.162 XRCC4 Arina Puzriakova gene: XRCC4 was added
gene: XRCC4 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: XRCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC4 were set to 25728776
Phenotypes for gene: XRCC4 were set to short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism
Monogenic short stature v0.161 WRN Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.161 WRN Arina Puzriakova gene: WRN was added
gene: WRN was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Werner syndrome
Monogenic short stature v0.160 THRB Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.160 THRB Arina Puzriakova gene: THRB was added
gene: THRB was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: THRB was set to Unknown
Monogenic short stature v0.159 TBCE Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.159 TBCE Arina Puzriakova gene: TBCE was added
gene: TBCE was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Monogenic short stature v0.158 SPRED1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.158 SPRED1 Arina Puzriakova gene: SPRED1 was added
gene: SPRED1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPRED1 were set to 19443465; 21548021; 21649642; 19366998; 17704776
Phenotypes for gene: SPRED1 were set to Legius Syndrome; Neurofibromatosis-like syndrome
Monogenic short stature v0.157 SOX3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.84
Monogenic short stature v0.157 SOX3 Arina Puzriakova gene: SOX3 was added
gene: SOX3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SOX3 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: SOX3 were set to 15800844
Phenotypes for gene: SOX3 were set to Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123; Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252; Panhypopituitarism, X-linked, OMIM:312000; Panhypopituitarism, X-linked, MONDO:0010712
Monogenic short stature v0.156 SOX2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.156 SOX2 Arina Puzriakova gene: SOX2 was added
gene: SOX2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic short stature v0.155 SMC3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.155 SMC3 Arina Puzriakova gene: SMC3 was added
gene: SMC3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMC3 were set to Cornelia De Lange
Monogenic short stature v0.154 SMC1A Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.154 SMC1A Arina Puzriakova gene: SMC1A was added
gene: SMC1A was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SMC1A were set to Cornelia de Lange syndrome 2, OMIM:300590; Cornelia de Lange syndrome 2, MONDO:0010370; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771
Monogenic short stature v0.153 SMARCAL1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.153 SMARCAL1 Arina Puzriakova gene: SMARCAL1 was added
gene: SMARCAL1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SMARCAL1 was set to Unknown
Monogenic short stature v0.152 SHOX2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.152 SHOX2 Arina Puzriakova gene: SHOX2 was added
gene: SHOX2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: SHOX2 was set to Unknown
Monogenic short stature v0.151 SAMD9 Arina Puzriakova Entity copied from Growth failure in early childhood v3.83
Monogenic short stature v0.151 SAMD9 Arina Puzriakova gene: SAMD9 was added
gene: SAMD9 was added to Monogenic short stature. Sources: Expert Review Red
missense tags were added to gene: SAMD9.
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, 617053
Monogenic short stature v0.150 RPS6KA3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.82
Monogenic short stature v0.150 RPS6KA3 Arina Puzriakova gene: RPS6KA3 was added
gene: RPS6KA3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: RPS6KA3 were set to Coffin Lowry
Monogenic short stature v0.149 RPL10 Arina Puzriakova Entity copied from Growth failure in early childhood v3.82
Monogenic short stature v0.149 RPL10 Arina Puzriakova gene: RPL10 was added
gene: RPL10 was added to Monogenic short stature. Sources: Expert Review Red
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
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35
Monogenic short stature v0.148 ROR2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.82
Monogenic short stature v0.148 ROR2 Arina Puzriakova gene: ROR2 was added
gene: ROR2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: ROR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ROR2 were set to Robinow syndrome, autosomal recessive, OMIM:268310
Monogenic short stature v0.147 RNU4ATAC Arina Puzriakova Entity copied from Growth failure in early childhood v3.82
Monogenic short stature v0.147 RNU4ATAC Arina Puzriakova gene: RNU4ATAC was added
gene: RNU4ATAC was added to Monogenic short stature. Sources: Expert Review Red
locus-type-rna-small-nuclear tags were added to gene: RNU4ATAC.
Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU4ATAC were set to 21474760
Phenotypes for gene: RNU4ATAC were set to MOPD I
Monogenic short stature v0.146 RBBP8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.82
Monogenic short stature v0.146 RBBP8 Arina Puzriakova gene: RBBP8 was added
gene: RBBP8 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBBP8 were set to 24389050; 21998596
Phenotypes for gene: RBBP8 were set to seckel syndrome but with proportionate head/height impairment, cafe au lair macules
Monogenic short stature v0.145 RAPSN Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.145 RAPSN Arina Puzriakova gene: RAPSN was added
gene: RAPSN was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: RAPSN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAPSN were set to Fetal akinesia deformation sequence 2, OMIM:618388; Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, OMIM:616326
Monogenic short stature v0.144 RAD21 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.144 RAD21 Arina Puzriakova gene: RAD21 was added
gene: RAD21 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD21 were set to Cornelia de Lange syndrome 4, OMIM:614701
Monogenic short stature v0.143 PROP1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.143 PROP1 Arina Puzriakova gene: PROP1 was added
gene: PROP1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined
Monogenic short stature v0.142 PROKR2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.142 PROKR2 Arina Puzriakova gene: PROKR2 was added
gene: PROKR2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: PROKR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROKR2 were set to 22319038
Phenotypes for gene: PROKR2 were set to hypopituitarism, Hypoplastic corpus callosum, normal or small anterior pituitary, Club foot, syrinx spinal cord, microcephaly, epilepsy
Monogenic short stature v0.141 POU1F1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.141 POU1F1 Arina Puzriakova gene: POU1F1 was added
gene: POU1F1 was added to Monogenic short stature. Sources: Expert Review Red
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 or isolated, 1, OMIM:613038; Variable degree of TSH deficiency
Monogenic short stature v0.140 PNPLA6 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.140 PNPLA6 Arina Puzriakova gene: PNPLA6 was added
gene: PNPLA6 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 25480986
Phenotypes for gene: PNPLA6 were set to Oliver-Mcfarlane syndrome, Trichomegaly, GH deficiency, retinal dystrophy, hypogonadotrophic hypogonadism
Monogenic short stature v0.139 PITX2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.139 PITX2 Arina Puzriakova gene: PITX2 was added
gene: PITX2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: PITX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PITX2 were set to AXENFELD-RIEGER SYNDROME
Monogenic short stature v0.138 PCNT Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.138 PCNT Arina Puzriakova gene: PCNT was added
gene: PCNT was added to Monogenic short stature. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCNT were set to 18157127; 18174396
Phenotypes for gene: PCNT were set to MOPDII; Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance, 210720
Monogenic short stature v0.137 PAPPA2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.137 PAPPA2 Arina Puzriakova gene: PAPPA2 was added
gene: PAPPA2 was added to Monogenic short stature. Sources: Expert Review Red,NHS GMS
gene-checked tags were added to gene: PAPPA2.
Mode of inheritance for gene: PAPPA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAPPA2 were set to 26902202; 33875846
Phenotypes for gene: PAPPA2 were set to Short stature, Dauber-Argente type, OMIM:619489
Monogenic short stature v0.136 OTX2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.136 OTX2 Arina Puzriakova gene: OTX2 was added
gene: OTX2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTX2 were set to 18728160
Phenotypes for gene: OTX2 were set to Microcephaly, bilateral anopthalmia, developmental delay, cleft palate
Monogenic short stature v0.135 ORC6 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.135 ORC6 Arina Puzriakova gene: ORC6 was added
gene: ORC6 was added to Monogenic short stature. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: ORC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC6 were set to 21358632
Phenotypes for gene: ORC6 were set to Meier-Gorlin syndrome 3, OMIM:613803
Monogenic short stature v0.134 ORC4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.134 ORC4 Arina Puzriakova gene: ORC4 was added
gene: ORC4 was added to Monogenic short stature. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: ORC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC4 were set to 21358632
Phenotypes for gene: ORC4 were set to Meier-Gorlin syndrome 2, OMIM:613800
Monogenic short stature v0.133 ORC1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.133 ORC1 Arina Puzriakova gene: ORC1 was added
gene: ORC1 was added to Monogenic short stature. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: ORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC1 were set to 21358632
Phenotypes for gene: ORC1 were set to Meier-Gorlin syndrome 1, OMIM:224690
Monogenic short stature v0.132 NIPBL Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.132 NIPBL Arina Puzriakova gene: NIPBL was added
gene: NIPBL was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: NIPBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NIPBL were set to Cornelia De Lange
Monogenic short stature v0.131 MCM5 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.131 MCM5 Arina Puzriakova gene: MCM5 was added
gene: MCM5 was added to Monogenic short stature. Sources: Expert Review Red
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
Monogenic short stature v0.130 LIG4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.81
Monogenic short stature v0.130 LIG4 Arina Puzriakova gene: LIG4 was added
gene: LIG4 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: LIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG4 were set to 11779494; 16088910
Phenotypes for gene: LIG4 were set to microcephaly, growth retardation, immunodeficiency, developmental delay
Monogenic short stature v0.129 LIG1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.80
Monogenic short stature v0.129 LIG1 Arina Puzriakova gene: LIG1 was added
gene: LIG1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 1581963; 1351188
Phenotypes for gene: LIG1 were set to immunodeficiency, sun sensitivity, growth reatrdation
Monogenic short stature v0.128 LHX4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.128 LHX4 Arina Puzriakova gene: LHX4 was added
gene: LHX4 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: LHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX4 were set to 11567216, 18073311
Phenotypes for gene: LHX4 were set to hypopituitarism
Monogenic short stature v0.127 LHX3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.127 LHX3 Arina Puzriakova gene: LHX3 was added
gene: LHX3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: LHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LHX3 were set to GH, TSH, LH, FSH, PRL deficiencies
Monogenic short stature v0.126 KMT2D Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.126 KMT2D Arina Puzriakova gene: KMT2D was added
gene: KMT2D was added to Monogenic short stature. Sources: Expert Review Red,NHS GMS
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to 31949313; 32083401; 21882399
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, OMIM:147920
Monogenic short stature v0.125 KHDC3L Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.125 KHDC3L Arina Puzriakova gene: KHDC3L was added
gene: KHDC3L was added to Monogenic short stature. Sources: Expert list,Expert Review Red
watchlist tags were added to gene: KHDC3L.
Mode of inheritance for gene: KHDC3L was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: KHDC3L were set to 29574422
Phenotypes for gene: KHDC3L were set to IUGR; Failure to thrive; Hydatidiform mole, recurrent, 2 OMIM:614293; hydatidiform mole, recurrent, 2 MONDO:0013671; pregnancy loss
Penetrance for gene: KHDC3L were set to unknown
Monogenic short stature v0.124 KDM6A Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.124 KDM6A Arina Puzriakova gene: KDM6A was added
gene: KDM6A was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: KDM6A 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: KDM6A were set to 23913813; 29914387; 31654559; 33674768
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2, OMIM:300867
Monogenic short stature v0.123 INTS8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.123 INTS8 Arina Puzriakova gene: INTS8 was added
gene: INTS8 was added to Monogenic short stature. Sources: Literature
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS8 were set to 28542170
Phenotypes for gene: INTS8 were set to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Monogenic short stature v0.122 INSR Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.122 INSR Arina Puzriakova gene: INSR was added
gene: INSR was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: INSR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INSR were set to Leprechaunism
Monogenic short stature v0.121 IGFBP3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.121 IGFBP3 Arina Puzriakova gene: IGFBP3 was added
gene: IGFBP3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: IGFBP3 was set to Unknown
Publications for gene: IGFBP3 were set to 10364674
Phenotypes for gene: IGFBP3 were set to Silver Russell Syndrome
Monogenic short stature v0.120 IGFBP1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.120 IGFBP1 Arina Puzriakova gene: IGFBP1 was added
gene: IGFBP1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: IGFBP1 was set to Unknown
Publications for gene: IGFBP1 were set to 10364674
Phenotypes for gene: IGFBP1 were set to Silver-Russell Syndrome
Monogenic short stature v0.119 IFT172 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.119 IFT172 Arina Puzriakova gene: IFT172 was added
gene: IFT172 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: IFT172 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT172 were set to 25664603
Phenotypes for gene: IFT172 were set to GH deficiency, retinopathy, metaphyseal dysplasia
Monogenic short stature v0.118 HESX1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.118 HESX1 Arina Puzriakova gene: HESX1 was added
gene: HESX1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: HESX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HESX1 were set to Growth hormone deficiency with pituitary anomalies, OMIM:182230; Pituitary hormone deficiency, combined, 5, OMIM:182230; Septooptic dysplasia, OMIM:182230
Monogenic short stature v0.117 HDAC8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.117 HDAC8 Arina Puzriakova gene: HDAC8 was added
gene: HDAC8 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: HDAC8 were set to Cornelia De Lange
Monogenic short stature v0.116 H19 Arina Puzriakova Entity copied from Growth failure in early childhood v3.79
Monogenic short stature v0.116 H19 Arina Puzriakova gene: H19 was added
gene: H19 was added to Monogenic short stature. Sources: Expert Review Red
locus-type-rna-long-non-coding tags were added to gene: H19.
Mode of inheritance for gene: H19 was set to Other
Phenotypes for gene: H19 were set to Russell-Silver syndrome
Monogenic short stature v0.115 GPR161 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.115 GPR161 Arina Puzriakova gene: GPR161 was added
gene: GPR161 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: GPR161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR161 were set to 25322266
Phenotypes for gene: GPR161 were set to Short stature with hypopituitarism, intellectual disability, sparse or absent hair in the frontal area, hypotelorism, broad nasal root, thick alae nasi, nail hypoplasia, short fifth finger, 2-3 toe syndactyl. MRI showed hypoplastic pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pituitary stalk
Monogenic short stature v0.114 GLI3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.114 GLI3 Arina Puzriakova gene: GLI3 was added
gene: GLI3 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 9054938
Phenotypes for gene: GLI3 were set to Pallister-Hall syndrome
Monogenic short stature v0.113 GLI2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.113 GLI2 Arina Puzriakova gene: GLI2 was added
gene: GLI2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GLI2 were set to Holoprosencephaly, hypopituitarism
Monogenic short stature v0.112 GINS3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.112 GINS3 Arina Puzriakova gene: GINS3 was added
gene: GINS3 was added to Monogenic short stature. Sources: Expert Review Red,Literature
gene-checked tags were added to gene: GINS3.
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome like; Meier-Gorlin syndrome, MONDO:0016817
Penetrance for gene: GINS3 were set to unknown
Mode of pathogenicity for gene: GINS3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.111 GINS2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.111 GINS2 Arina Puzriakova gene: GINS2 was added
gene: GINS2 was added to Monogenic short stature. Sources: Literature,Expert Review Red
Mode of inheritance for gene: GINS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS2 were set to 34353863
Phenotypes for gene: GINS2 were set to Meier-Gorlin syndrome like; Meier-Gorlin syndrome, MONDO:0016817
Penetrance for gene: GINS2 were set to unknown
Mode of pathogenicity for gene: GINS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.110 GHSR Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.110 GHSR Arina Puzriakova gene: GHSR was added
gene: GHSR was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: GHSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GHSR were set to 16511605
Phenotypes for gene: GHSR were set to Idiopathic short stature, GH deficiency
Monogenic short stature v0.109 GHRHR Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.109 GHRHR Arina Puzriakova gene: GHRHR was added
gene: GHRHR was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHRHR were set to Growth hormone deficiency
Monogenic short stature v0.108 GH1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.108 GH1 Arina Puzriakova gene: GH1 was added
gene: GH1 was added to Monogenic short stature. Sources: Expert Review Red
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
Monogenic short stature v0.107 FGFR1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.107 FGFR1 Arina Puzriakova gene: FGFR1 was added
gene: FGFR1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to 22319038
Monogenic short stature v0.106 FGF8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.106 FGF8 Arina Puzriakova gene: FGF8 was added
gene: FGF8 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF8 were set to 22319038
Phenotypes for gene: FGF8 were set to hypopituitarism, absent corpus callosum, Holoprosencephaly, Moebius syndrome, craniofacial defects, high arched palate, maxillary hypoplasia, microcepahly, spastic diplegia
Monogenic short stature v0.105 FGD1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.105 FGD1 Arina Puzriakova gene: FGD1 was added
gene: FGD1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FGD1 were set to Aarskog
Monogenic short stature v0.104 FANCM Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.104 FANCM Arina Puzriakova gene: FANCM was added
gene: FANCM was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: FANCM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCM were set to 16116422; 19423727; 25078778
Phenotypes for gene: FANCM were set to Fanconi anemia, complementation group M, 614087
Monogenic short stature v0.103 ERCC8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.103 ERCC8 Arina Puzriakova gene: ERCC8 was added
gene: ERCC8 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC8 were set to cockayne
Monogenic short stature v0.102 ERCC6 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.102 ERCC6 Arina Puzriakova gene: ERCC6 was added
gene: ERCC6 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC6 were set to Cockayne syndrome, type B, 133540
Monogenic short stature v0.101 EPHX1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.101 EPHX1 Arina Puzriakova gene: EPHX1 was added
gene: EPHX1 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: EPHX1 was set to Unknown
Phenotypes for gene: EPHX1 were set to ?Fetal hydantoin syndromeDiphenylhydantoin toxicityHypercholanemia, familial, 607748{Preeclampsia, susceptibility to}, 189800
Monogenic short stature v0.100 EP300 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.100 EP300 Arina Puzriakova gene: EP300 was added
gene: EP300 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EP300 were set to Rubenstein Taybi
Monogenic short stature v0.99 DOK7 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.99 DOK7 Arina Puzriakova gene: DOK7 was added
gene: DOK7 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: DOK7 was set to Unknown
Phenotypes for gene: DOK7 were set to Myasthenia, limb-girdle, familial, 254300Fetal akinesia deformation sequence, 208150
Monogenic short stature v0.98 DNA2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.98 DNA2 Arina Puzriakova gene: DNA2 was added
gene: DNA2 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 24389050; 31045292
Phenotypes for gene: DNA2 were set to Seckel syndrome 8, OMIM:615807
Monogenic short stature v0.97 DHCR7 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.97 DHCR7 Arina Puzriakova gene: DHCR7 was added
gene: DHCR7 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHCR7 were set to Smith Lemli Opitz
Monogenic short stature v0.96 CRIPT Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.96 CRIPT Arina Puzriakova gene: CRIPT was added
gene: CRIPT was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRIPT were set to PMC3912419
Phenotypes for gene: CRIPT were set to frontal bossing, high forehead, sparse hair and eyebrows, telecanthus, mild proptosis (staring look), upturned nostrils, and hypoplastic terminal phalanges with brachydactyly
Monogenic short stature v0.95 CREBBP Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.95 CREBBP Arina Puzriakova gene: CREBBP was added
gene: CREBBP was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CREBBP were set to Rubenstein Taybi
Monogenic short stature v0.94 COL1A1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.94 COL1A1 Arina Puzriakova gene: COL1A1 was added
gene: COL1A1 was added to Monogenic short stature. Sources: Expert list
Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COL1A1 were set to OI; Osteogenesis imperfecta, type II, 166210; Osteogenesis imperfecta, type III, 259420; Osteogenesis imperfecta, type I, 166200; Osteogenesis imperfecta, type IV, 166220
Monogenic short stature v0.93 CHD7 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.93 CHD7 Arina Puzriakova gene: CHD7 was added
gene: CHD7 was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD7 were set to 16400610
Phenotypes for gene: CHD7 were set to CHARGE syndrome - ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation; CHARGE syndrome, 214800
Monogenic short stature v0.92 CENPJ Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.92 CENPJ Arina Puzriakova gene: CENPJ was added
gene: CENPJ was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPJ were set to 20522431
Phenotypes for gene: CENPJ were set to seckel syndrome
Monogenic short stature v0.91 CDT1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.91 CDT1 Arina Puzriakova gene: CDT1 was added
gene: CDT1 was added to Monogenic short stature. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: CDT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDT1 were set to 21358632
Phenotypes for gene: CDT1 were set to Meier-Gorlin syndrome 4, OMIM:613804
Monogenic short stature v0.90 CDC6 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.90 CDC6 Arina Puzriakova gene: CDC6 was added
gene: CDC6 was added to Monogenic short stature. Sources: Expert Review Red,Expert list
Mode of inheritance for gene: CDC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC6 were set to 21358632
Phenotypes for gene: CDC6 were set to ?Meier-Gorlin syndrome 5, 613805; patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia
Monogenic short stature v0.89 ATRX Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.89 ATRX Arina Puzriakova gene: ATRX was added
gene: ATRX was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: ATRX was set to Unknown
Phenotypes for gene: ATRX were set to SGA, which is sometimes called intrauterine growth restriction (IUGR),
Monogenic short stature v0.88 ATRIP Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.88 ATRIP Arina Puzriakova gene: ATRIP was added
gene: ATRIP was added to Monogenic short stature. Sources: Expert Review Red
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 23144622
Phenotypes for gene: ATRIP were set to microcephaly, micrognathia, small ear lobes, dental crowding
Monogenic short stature v0.87 A2ML1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.87 A2ML1 Arina Puzriakova gene: A2ML1 was added
gene: A2ML1 was added to Monogenic short stature. Sources: Expert list,Expert Review Red,NHS GMS
Mode of inheritance for gene: A2ML1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: A2ML1 were set to 24939586; 25862627
Phenotypes for gene: A2ML1 were set to Noonan syndrome
Monogenic short stature v0.86 ZNF668 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.86 ZNF668 Arina Puzriakova gene: ZNF668 was added
gene: ZNF668 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: ZNF668.
Mode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF668 were set to 34313816; 26633546
Phenotypes for gene: ZNF668 were set to Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, OMIM:620194
Monogenic short stature v0.85 VPS50 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.85 VPS50 Arina Puzriakova gene: VPS50 was added
gene: VPS50 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: VPS50.
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to 34037727
Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis, OMIM:619685
Penetrance for gene: VPS50 were set to Complete
Monogenic short stature v0.84 SETD5 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.84 SETD5 Arina Puzriakova gene: SETD5 was added
gene: SETD5 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 28881385
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, autosomal dominant 23, OMIM:615761
Penetrance for gene: SETD5 were set to Incomplete
Monogenic short stature v0.83 RECQL4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.83 RECQL4 Arina Puzriakova gene: RECQL4 was added
gene: RECQL4 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
Q1_24_promote_green, Q1_24_NHS_review tags were added to gene: RECQL4.
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to 25966250; 29462647; 31406625; 34155702; 35086131; 35781852; 37228773; 38021400
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome, type 2, OMIM:268400
Penetrance for gene: RECQL4 were set to Complete
Monogenic short stature v0.82 RASA2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.82 RASA2 Arina Puzriakova gene: RASA2 was added
gene: RASA2 was added to Monogenic short stature. Sources: NHS GMS,Expert list,Expert Review Amber
Mode of inheritance for gene: RASA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RASA2 were set to 25049390
Phenotypes for gene: RASA2 were set to Noonan syndrome
Monogenic short stature v0.81 RAP1B Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.81 RAP1B Arina Puzriakova gene: RAP1B was added
gene: RAP1B was added to Monogenic short stature. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: RAP1B.
Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAP1B were set to 32627184; 26280580
Phenotypes for gene: RAP1B were set to Syndromic intellectual disability; short stature
Monogenic short stature v0.80 RAD51 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.80 RAD51 Arina Puzriakova gene: RAD51 was added
gene: RAD51 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RAD51 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD51 were set to 26681308; 26253028; 30907510
Phenotypes for gene: RAD51 were set to Fanconi anemia, complementation group R, OMIM:617244
Monogenic short stature v0.79 PADI6 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.79 PADI6 Arina Puzriakova gene: PADI6 was added
gene: PADI6 was added to Monogenic short stature. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: PADI6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PADI6 were set to 32928291; 29574422; 33221824
Phenotypes for gene: PADI6 were set to Short stature; IUGR; miscarriages in the family; Preimplantation embryonic lethality 2 OMIM:617234; preimplantation embryonic lethality 2 MONDO:0014978; Beckwith-Wiedemann syndrome; Multi Locus Imprinting Disturbance
Penetrance for gene: PADI6 were set to unknown
Monogenic short stature v0.78 NLRP7 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.78 NLRP7 Arina Puzriakova gene: NLRP7 was added
gene: NLRP7 was added to Monogenic short stature. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP7 were set to 28561018
Phenotypes for gene: NLRP7 were set to IUGR; Short stature; fetal wastage; Multi Locus Imprinting Disturbance; Hydatidiform mole, recurrent, 1 OMIM:231090; hydatidiform mole, recurrent, 1 MONDO:0009273
Penetrance for gene: NLRP7 were set to unknown
Monogenic short stature v0.77 NLRP5 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.77 NLRP5 Arina Puzriakova gene: NLRP5 was added
gene: NLRP5 was added to Monogenic short stature. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: NLRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 26323243; 29574422
Phenotypes for gene: NLRP5 were set to IUGR; Short stature; Failure to thrive; body asymmetry; multilocus imprinting disturbances
Penetrance for gene: NLRP5 were set to unknown
Monogenic short stature v0.76 NLRP2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.76 NLRP2 Arina Puzriakova gene: NLRP2 was added
gene: NLRP2 was added to Monogenic short stature. Sources: Expert list,Expert Review Amber
watchlist tags were added to gene: NLRP2.
Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 26323243; 29574422; 19300480; 30877238; 33090377
Phenotypes for gene: NLRP2 were set to Maternal effect gene- causing phenotypes that include IUGR
Penetrance for gene: NLRP2 were set to unknown
Monogenic short stature v0.75 NF1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.75 NF1 Arina Puzriakova gene: NF1 was added
gene: NF1 was added to Monogenic short stature. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NF1 were set to 26178382; 27247625; 30602027; 35633639; 36373817
Phenotypes for gene: NF1 were set to Neurofibromatosis-Noonan syndrome, OMIM:601321
Monogenic short stature v0.74 MRAS Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.74 MRAS Arina Puzriakova gene: MRAS was added
gene: MRAS was added to Monogenic short stature. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718; 31173466; 31108500; 34080768
Phenotypes for gene: MRAS were set to Noonan syndrome 11, OMIM:618499
Monogenic short stature v0.73 MAPK1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.73 MAPK1 Arina Puzriakova gene: MAPK1 was added
gene: MAPK1 was added to Monogenic short stature. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Noonan syndrome 13, OMIM:619087
Mode of pathogenicity for gene: MAPK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.72 KDM3B Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.72 KDM3B Arina Puzriakova gene: KDM3B was added
gene: KDM3B was added to Monogenic short stature. Sources: Victorian Clinical Genetics Services,Expert Review Amber
watchlist tags were added to gene: KDM3B.
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KDM3B were set to 30929739
Phenotypes for gene: KDM3B were set to Diets-Jongmans syndrome, OMIM:618846; Diets-Jongmans syndrome, MONDO:0030012
Monogenic short stature v0.71 GGPS1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.71 GGPS1 Arina Puzriakova gene: GGPS1 was added
gene: GGPS1 was added to Monogenic short stature. Sources: Expert Review Amber,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, congenital hearing loss, and ovarian insufficiency syndrome, OMIM:619518
Monogenic short stature v0.70 FOXP4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.70 FOXP4 Arina Puzriakova gene: FOXP4 was added
gene: FOXP4 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
gene-checked tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Monogenic short stature v0.69 CCDC186 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.69 CCDC186 Arina Puzriakova gene: CCDC186 was added
gene: CCDC186 was added to Monogenic short stature. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: CCDC186.
Mode of inheritance for gene: CCDC186 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC186 were set to 33259146; 28600779
Phenotypes for gene: CCDC186 were set to failure to thrive and developmental delay
Monogenic short stature v0.68 BTK Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.68 BTK Arina Puzriakova gene: BTK was added
gene: BTK was added to Monogenic short stature. Sources: Expert Review Amber
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 8013627; 7849697; 9554752
Phenotypes for gene: BTK were set to Isolated growth hormone deficiency, type III, with agammaglobulinaemia, OMIM:307200
Monogenic short stature v0.67 ZFP57 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.67 ZFP57 Arina Puzriakova gene: ZFP57 was added
gene: ZFP57 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: ZFP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFP57 were set to 18622393
Phenotypes for gene: ZFP57 were set to Diabetes mellitus, transient neonatal 1, OMIM:601410
Monogenic short stature v0.66 UBE2T Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.66 UBE2T Arina Puzriakova gene: UBE2T was added
gene: UBE2T was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE2T were set to 26046368
Phenotypes for gene: UBE2T were set to Fanconi anemia, complementation group T, OMIM:616435
Monogenic short stature v0.65 TRIM37 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.65 TRIM37 Arina Puzriakova gene: TRIM37 was added
gene: TRIM37 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, OMIM:253250
Monogenic short stature v0.64 TOP3A Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.64 TOP3A Arina Puzriakova gene: TOP3A was added
gene: TOP3A was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: TOP3A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOP3A were set to Microcephaly, growth restriction, and increased sister chromatid exchange 2, OMIM:618097
Monogenic short stature v0.63 STAT5B Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.63 STAT5B Arina Puzriakova gene: STAT5B was added
gene: STAT5B was added to Monogenic short stature. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: STAT5B was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: STAT5B were set to 16787985; 15827093; 17030597; 26703237; 29844444
Phenotypes for gene: STAT5B were set to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985
Monogenic short stature v0.62 SRCAP Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.62 SRCAP Arina Puzriakova gene: SRCAP was added
gene: SRCAP was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SRCAP were set to Floating-Harbor syndrome, OMIM:136140
Monogenic short stature v0.61 SPRED2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.61 SPRED2 Arina Puzriakova gene: SPRED2 was added
gene: SPRED2 was added to Monogenic short stature. Sources: Expert Review Green,Literature,NHS GMS
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to 34626534
Phenotypes for gene: SPRED2 were set to Noonan syndrome 14, OMIM:619745
Monogenic short stature v0.60 SOS2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.78
Monogenic short stature v0.60 SOS2 Arina Puzriakova gene: SOS2 was added
gene: SOS2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOS2 were set to 26173643; 25795793
Phenotypes for gene: SOS2 were set to Noonan syndrome 9, OMIM:616559
Monogenic short stature v0.59 SOS1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.59 SOS1 Arina Puzriakova gene: SOS1 was added
gene: SOS1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOS1 were set to 17143285; 17143282; 17586837; 19438935
Phenotypes for gene: SOS1 were set to Noonan syndrome 4, OMIM:610733
Mode of pathogenicity for gene: SOS1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.58 SLX4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.58 SLX4 Arina Puzriakova gene: SLX4 was added
gene: SLX4 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLX4 were set to 21240277; 21240275
Phenotypes for gene: SLX4 were set to Fanconi anemia, complementation group P, OMIM:613951
Monogenic short stature v0.57 SHOX Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.57 SHOX Arina Puzriakova gene: SHOX was added
gene: SHOX was added to Monogenic short stature. Sources: Expert Review Green,NHS GMS
Pseudoautosomal region 1 tags were added to gene: SHOX.
Mode of inheritance for gene: SHOX was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: SHOX were set to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
Monogenic short stature v0.56 SHOC2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.56 SHOC2 Arina Puzriakova gene: SHOC2 was added
gene: SHOC2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHOC2 were set to 19684605; 22528146; 23918763
Phenotypes for gene: SHOC2 were set to Noonan syndrome-like with loose anagen hair 1, OMIM:607721
Mode of pathogenicity for gene: SHOC2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.55 RRAS2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.55 RRAS2 Arina Puzriakova gene: RRAS2 was added
gene: RRAS2 was added to Monogenic short stature. Sources: Expert Review Green,Expert Review,NHS GMS
Mode of inheritance for gene: RRAS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAS2 were set to 31130282
Phenotypes for gene: RRAS2 were set to Noonan syndrome 12, OMIM:618624
Mode of pathogenicity for gene: RRAS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.54 RNPC3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.54 RNPC3 Arina Puzriakova gene: RNPC3 was added
gene: RNPC3 was added to Monogenic short stature. Sources: Expert Review Green,NHS GMS
gene-checked tags were added to gene: RNPC3.
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 24480542; 29866761; 32462814; 33650182
Phenotypes for gene: RNPC3 were set to Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160
Monogenic short stature v0.53 RIT1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.53 RIT1 Arina Puzriakova gene: RIT1 was added
gene: RIT1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIT1 were set to 23791108; 25124994; 24939608
Phenotypes for gene: RIT1 were set to Noonan syndrome 8, OMIM:615355
Mode of pathogenicity for gene: RIT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.52 RAF1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.52 RAF1 Arina Puzriakova gene: RAF1 was added
gene: RAF1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAF1 were set to 17603483; 17603482
Phenotypes for gene: RAF1 were set to LEOPARD syndrome 2, OMIM:611554; Noonan syndrome 5, OMIM:611553
Mode of pathogenicity for gene: RAF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.51 PTPN11 Arina Puzriakova Entity copied from Growth failure in early childhood v3.77
Monogenic short stature v0.51 PTPN11 Arina Puzriakova gene: PTPN11 was added
gene: PTPN11 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 17603483; 11704759; 12529711; 12634870; 15384080; 15240615; 16263833; 17497712; 18678287
Phenotypes for gene: PTPN11 were set to LEOPARD syndrome 1, OMIM:151100; Noonan syndrome 1, OMIM:163950
Monogenic short stature v0.50 PPP1CB Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.50 PPP1CB Arina Puzriakova gene: PPP1CB was added
gene: PPP1CB was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP1CB were set to 27264673; 27681385; 28211982
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2, OMIM:617506
Monogenic short stature v0.49 PLK4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.49 PLK4 Arina Puzriakova gene: PLK4 was added
gene: PLK4 was added to Monogenic short stature. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PLK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK4 were set to 25344692; 25320347; 27650967
Phenotypes for gene: PLK4 were set to Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM:616171
Monogenic short stature v0.48 PLAG1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.48 PLAG1 Arina Puzriakova gene: PLAG1 was added
gene: PLAG1 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: PLAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLAG1 were set to 28796236
Phenotypes for gene: PLAG1 were set to Silver-Russell syndrome 4, OMIM:618907
Monogenic short stature v0.47 PIK3R1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.47 PIK3R1 Arina Puzriakova gene: PIK3R1 was added
gene: PIK3R1 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3R1 were set to SHORT syndrome, OMIM:269880
Monogenic short stature v0.46 PALB2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.46 PALB2 Arina Puzriakova gene: PALB2 was added
gene: PALB2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALB2 were set to 17200672; 17200671
Phenotypes for gene: PALB2 were set to Fanconi anemia, complementation group N, OMIM:610832
Monogenic short stature v0.45 OBSL1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.45 OBSL1 Arina Puzriakova gene: OBSL1 was added
gene: OBSL1 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: OBSL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OBSL1 were set to 21737058
Phenotypes for gene: OBSL1 were set to 3-M syndrome 2, OMIM:612921
Monogenic short stature v0.44 NRAS Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.44 NRAS Arina Puzriakova gene: NRAS was added
gene: NRAS was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRAS were set to 19966803; 19775298
Phenotypes for gene: NRAS were set to Noonan syndrome 6, OMIM:613224
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
Monogenic short stature v0.43 NPR2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.43 NPR2 Arina Puzriakova gene: NPR2 was added
gene: NPR2 was added to Monogenic short stature. Sources: NHS GMS,Expert list,Expert Review Green
Mode of inheritance for gene: NPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPR2 were set to Acromesomelic dysplasia 1, Maroteaux type, OMIM:602875
Monogenic short stature v0.42 NHLRC2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.42 NHLRC2 Arina Puzriakova gene: NHLRC2 was added
gene: NHLRC2 was added to Monogenic short stature. Sources: Expert Review Green,Literature
gene-checked tags were added to gene: NHLRC2.
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to FINCA syndrome, OMIM:618278
Monogenic short stature v0.41 NBN Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.41 NBN Arina Puzriakova gene: NBN was added
gene: NBN was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NBN were set to Nijmegen breakage syndrome, OMIM:251260
Monogenic short stature v0.40 NBAS Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.40 NBAS Arina Puzriakova gene: NBAS was added
gene: NBAS was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 31761904
Phenotypes for gene: NBAS were set to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, OMIM:614800
Monogenic short stature v0.39 MTX2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.39 MTX2 Arina Puzriakova gene: MTX2 was added
gene: MTX2 was added to Monogenic short stature. Sources: Expert Review Green,Expert Review,Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia progeroid syndrome, OMIM:619127
Monogenic short stature v0.38 MSTO1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.38 MSTO1 Arina Puzriakova gene: MSTO1 was added
gene: MSTO1 was added to Monogenic short stature. Sources: Expert Review Green,Literature,NHS GMS
Q1_24_MOI, Q1_24_NHS_review tags were added to gene: MSTO1.
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 29339779; 28544275; 31604776; 31130378; 28554942; 37431817
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, OMIM:617675
Monogenic short stature v0.37 MAP2K2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.37 MAP2K2 Arina Puzriakova gene: MAP2K2 was added
gene: MAP2K2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: MAP2K2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K2 were set to 16439621; 21396583; 23379592
Phenotypes for gene: MAP2K2 were set to Cardiofaciocutaneous syndrome 4, OMIM:615280
Mode of pathogenicity for gene: MAP2K2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.36 MAP2K1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.36 MAP2K1 Arina Puzriakova gene: MAP2K1 was added
gene: MAP2K1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to 16825433; 16439621; 21396583; 23321623
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome 3, OMIM:615279
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
Monogenic short stature v0.35 LZTR1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.35 LZTR1 Arina Puzriakova gene: LZTR1 was added
gene: LZTR1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to 29469822; 25795793
Phenotypes for gene: LZTR1 were set to Noonan syndrome 10, OMIM:616564 (AD); Noonan syndrome 2, OMIM:605275 (AR)
Monogenic short stature v0.34 KRAS Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.34 KRAS Arina Puzriakova gene: KRAS was added
gene: KRAS was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 21396583
Phenotypes for gene: KRAS were set to Cardiofaciocutaneous syndrome 2, OMIM:615278; Noonan syndrome 3, OMIM:609942
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.33 INTS1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.33 INTS1 Arina Puzriakova gene: INTS1 was added
gene: INTS1 was added to Monogenic short stature. Sources: Expert Review Green,Literature
Mode of inheritance for gene: INTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS1 were set to 28542170; 30622326; 31428919
Phenotypes for gene: INTS1 were set to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571
Monogenic short stature v0.32 IGFALS Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.32 IGFALS Arina Puzriakova gene: IGFALS was added
gene: IGFALS was added to Monogenic short stature. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: IGFALS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGFALS were set to 14762184; 16507628; 17726072; 18303074; 20591980; 21396577; 23488611; 24819402; 24423360; 27018247; 30717585; 36348166
Phenotypes for gene: IGFALS were set to Acid-labile subunit, deficiency of, OMIM:615961
Monogenic short stature v0.31 IGF2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.31 IGF2 Arina Puzriakova gene: IGF2 was added
gene: IGF2 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: IGF2 were set to 26154720
Phenotypes for gene: IGF2 were set to Silver-Russell syndrome 3, OMIM:616489
Monogenic short stature v0.30 IGF1R Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.30 IGF1R Arina Puzriakova gene: IGF1R was added
gene: IGF1R was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: IGF1R was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IGF1R were set to Insulin-like growth factor I, resistance to, OMIM:270450
Monogenic short stature v0.29 IGF1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.29 IGF1 Arina Puzriakova gene: IGF1 was added
gene: IGF1 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: IGF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IGF1 were set to Insulin-like growth factor I deficiency, OMIM:608747
Monogenic short stature v0.28 HRAS Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.28 HRAS Arina Puzriakova gene: HRAS was added
gene: HRAS was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HRAS were set to 16170316; 16969868; 16443854; 21396583
Phenotypes for gene: HRAS were set to Costello syndrome, OMIM:218040
Mode of pathogenicity for gene: HRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.27 HMGA2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.27 HMGA2 Arina Puzriakova gene: HMGA2 was added
gene: HMGA2 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: HMGA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGA2 were set to 29655892
Phenotypes for gene: HMGA2 were set to Silver-Russell syndrome 5, OMIM:618908
Monogenic short stature v0.26 GHR Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.26 GHR Arina Puzriakova gene: GHR was added
gene: GHR was added to Monogenic short stature. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Laron dwarfism, OMIM:262500
Monogenic short stature v0.25 FGFR3 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.25 FGFR3 Arina Puzriakova gene: FGFR3 was added
gene: FGFR3 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FGFR3 were set to Hypochondroplasia, OMIM:146000; Crouzon syndrome with acanthosis nigricans, OMIM:612247; Thanatophoric dysplasia, type I, OMIM:187600; Thanatophoric dysplasia, type II, OMIM:187601
Monogenic short stature v0.24 FANCL Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.24 FANCL Arina Puzriakova gene: FANCL was added
gene: FANCL was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCL were set to 16474160; 12724401; 25754594; 12973351; 19405097
Phenotypes for gene: FANCL were set to Fanconi anemia, complementation group L, OMIM:614083
Monogenic short stature v0.23 FANCI Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.23 FANCI Arina Puzriakova gene: FANCI was added
gene: FANCI was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 17452773; 11239453
Phenotypes for gene: FANCI were set to Fanconi anemia, complementation group I, OMIM:609053
Monogenic short stature v0.22 FANCG Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.22 FANCG Arina Puzriakova gene: FANCG was added
gene: FANCG was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCG were set to 16493006; 9806548
Phenotypes for gene: FANCG were set to Fanconi anemia, complementation group G, OMIM:614082
Monogenic short stature v0.21 FANCF Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.21 FANCF Arina Puzriakova gene: FANCF was added
gene: FANCF was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCF were set to 10615118
Phenotypes for gene: FANCF were set to Fanconi anemia, complementation group F, OMIM:603467
Monogenic short stature v0.20 FANCE Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.20 FANCE Arina Puzriakova gene: FANCE was added
gene: FANCE was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCE were set to 9147877; 9382107; 10205272; 7662964
Phenotypes for gene: FANCE were set to Fanconi anemia, complementation group E, OMIM:600901
Monogenic short stature v0.19 FANCD2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.19 FANCD2 Arina Puzriakova gene: FANCD2 was added
gene: FANCD2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCD2 were set to 11239454
Phenotypes for gene: FANCD2 were set to Fanconi anemia, complementation group D2, OMIM:227646
Monogenic short stature v0.18 FANCC Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.18 FANCC Arina Puzriakova gene: FANCC was added
gene: FANCC was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCC were set to 16493006; 1574115
Phenotypes for gene: FANCC were set to Fanconi anemia, complementation group C, OMIM:227645
Monogenic short stature v0.17 FANCB Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.17 FANCB Arina Puzriakova gene: FANCB was added
gene: FANCB was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FANCB were set to Fanconi anemia, complementation group B, OMIM:300514
Monogenic short stature v0.16 FANCA Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.16 FANCA Arina Puzriakova gene: FANCA was added
gene: FANCA was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCA were set to 16493006; 8896563
Phenotypes for gene: FANCA were set to Fanconi anemia, complementation group A, OMIM:227650
Monogenic short stature v0.15 ERCC4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.15 ERCC4 Arina Puzriakova gene: ERCC4 was added
gene: ERCC4 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC4 were set to 24027083; 23623386; 23623389
Phenotypes for gene: ERCC4 were set to Fanconi anemia, complementation group Q, OMIM:615272
Monogenic short stature v0.14 CUL7 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.14 CUL7 Arina Puzriakova gene: CUL7 was added
gene: CUL7 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: CUL7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CUL7 were set to 3-M syndrome 1, OMIM:273750
Monogenic short stature v0.13 COG4 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.13 COG4 Arina Puzriakova gene: COG4 was added
gene: COG4 was added to Monogenic short stature. Sources: Expert Review Green,Literature
Mode of inheritance for gene: COG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COG4 were set to 31949312; 30290151
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM:618150
Mode of pathogenicity for gene: COG4 was set to Other
Monogenic short stature v0.12 CEP57 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.12 CEP57 Arina Puzriakova gene: CEP57 was added
gene: CEP57 was added to Monogenic short stature. Sources: Expert Review Green,Other
Mode of inheritance for gene: CEP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP57 were set to 24259107; 21552266
Phenotypes for gene: CEP57 were set to Mosaic variegated aneuploidy syndrome 2, OMIM:614114
Monogenic short stature v0.11 CDKN1C Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.11 CDKN1C Arina Puzriakova gene: CDKN1C was added
gene: CDKN1C was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for gene: CDKN1C were set to IMAGE syndrome, OMIM:614732
Monogenic short stature v0.10 CCDC8 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.10 CCDC8 Arina Puzriakova gene: CCDC8 was added
gene: CCDC8 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: CCDC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC8 were set to 21737058
Phenotypes for gene: CCDC8 were set to 3-M syndrome 3, OMIM:614205
Monogenic short stature v0.9 CBL Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.9 CBL Arina Puzriakova gene: CBL was added
gene: CBL was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBL were set to 20619386; 20543203; 19571318
Phenotypes for gene: CBL were set to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic short stature v0.8 BRIP1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.8 BRIP1 Arina Puzriakova gene: BRIP1 was added
gene: BRIP1 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRIP1 were set to 16116423; 16116424; 16153896; 14630800
Phenotypes for gene: BRIP1 were set to Fanconi anemia, complementation group J, OMIM:609054
Monogenic short stature v0.7 BRCA2 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.7 BRCA2 Arina Puzriakova gene: BRCA2 was added
gene: BRCA2 was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRCA2 were set to 14670928; 28185119; 11239453; 12065746; 24395671
Phenotypes for gene: BRCA2 were set to Fanconi anemia, complementation group D1, OMIM:605724
Monogenic short stature v0.6 BRAF Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.6 BRAF Arina Puzriakova gene: BRAF was added
gene: BRAF was added to Monogenic short stature. Sources: Expert Review Green
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 16825433; 16474404; 19206169; 21396583
Phenotypes for gene: BRAF were set to Cardiofaciocutaneous syndrome, OMIM:115150; LEOPARD syndrome 3, OMIM:613707; Noonan syndrome 7, OMIM:613706
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
Monogenic short stature v0.5 BLM Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.5 BLM Arina Puzriakova gene: BLM was added
gene: BLM was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLM were set to Bloom syndrome, OMIM:210900
Monogenic short stature v0.4 ANKRD11 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.4 ANKRD11 Arina Puzriakova gene: ANKRD11 was added
gene: ANKRD11 was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: ANKRD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD11 were set to 21782149
Phenotypes for gene: ANKRD11 were set to KBG syndrome, OMIM:148050
Monogenic short stature v0.3 ANAPC1 Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.3 ANAPC1 Arina Puzriakova gene: ANAPC1 was added
gene: ANAPC1 was added to Monogenic short stature. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ANAPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC1 were set to 31303264
Phenotypes for gene: ANAPC1 were set to Rothmund Thomson syndrome type 1, OMIM:618625
Monogenic short stature v0.2 ACAN Arina Puzriakova Entity copied from Growth failure in early childhood v3.76
Monogenic short stature v0.2 ACAN Arina Puzriakova gene: ACAN was added
gene: ACAN was added to Monogenic short stature. Sources: Expert list,Expert Review Green
Mode of inheritance for gene: ACAN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ACAN were set to 24762113; 27870580
Phenotypes for gene: ACAN were set to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM:165800 (AD); ?Spondyloepiphyseal dysplasia, Kimberley type, OMIM:608361 (AD); Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM:612813 (AR)
Intellectual disability v5.506 SRCAP Arina Puzriakova Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome, 136140; FLOATING-HARBOR SYNDROME to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, OMIM:619595; Floating-Harbor syndrome, OMIM:136140
Monogenic short stature v0.1 Arina Puzriakova List of related panels changed from to R453
Monogenic short stature v0.0 Arina Puzriakova Added Panel Monogenic short stature
Set panel types to: GMS Rare Disease Virtual; GMS Rare Disease
Fetal anomalies v3.146 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from RAPADILINO SYNDROME; ROTHMUND-THOMSON SYNDROME; BALLER-GEROLD SYNDROME to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Non-syndromic familial congenital anorectal malformations v1.9 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome 218600; Rothmund-Thomson syndrome 268400 to Baller-Gerold syndrome, OMIM:218600; Rothmund-Thomson syndrome, type 2, OMIM:268400
Cutaneous photosensitivity with a likely genetic cause v3.5 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson syndrome, 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400
Primary immunodeficiency or monogenic inflammatory bowel disease v4.196 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Combined immunodeficiency; Rothmund-Thomson syndrome, 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400; Combined immunodeficiency
Bilateral congenital or childhood onset cataracts v4.9 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson syndrome, 268400; RAPADILINO syndrome, 266280; Baller-Gerold syndrome, 218600; Rothmund-Thomson syndrome to Rothmund-Thomson syndrome, type 2, OMIM:268400
Pigmentary skin disorders v3.11 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thompson syndrome; RTS2; RAPADILINO SYNDROME, ROTHMUND-THOMSON SYNDROME, TYPE 2 to Baller-Gerold syndrome, OMIM:218600; Rothmund-Thomson syndrome, type 2, OMIM:268400
Childhood solid tumours cancer susceptibility v1.27 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund Thomson Syndrome to Rothmund-Thomson syndrome, type 2, OMIM:268400
Sarcoma cancer susceptibility v1.25 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson, Beller-Gerold and RAPADALINO syndromes; Osteosarcoma to Rothmund-Thomson syndrome, type 2, OMIM:268400; Osteosarcoma
Childhood solid tumours v4.16 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Rothmund Thomson Syndrome; 268400 to Rothmund-Thomson syndrome, type 2, OMIM:268400
Skeletal dysplasia v4.54 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from RAPILINO syndrome 266280; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome 218600 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Limb disorders v4.18 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome 218600; RAPILINO syndrome 266280; RAPILINO syndrome, 266280; Rothmund-Thomson syndrome, 268400; Rothmund-Thomson syndrome 268400; Baller-Gerold syndrome, 218600 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Radial dysplasia v1.24 RECQL4 Arina Puzriakova Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome, 218600; RAPILINO syndrome, 266280; Rothmund-Thomson syndrome, 268400 to Baller-Gerold syndrome, OMIM:218600; RAPADILINO syndrome, OMIM:266280; Rothmund-Thomson syndrome, type 2, OMIM:268400
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova changed review comment from: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, one of the most the most prominent of features is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.; to: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, the most prominent feature is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Classified gene: ABHD5 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Chanarin-Dorfman, caused by biallelic variants in the ABHD5 gene, is a neutral lipid storage disorder. The phenotype is variable with multiple organ involvement; however, one of the most the most prominent of features is non-bullous congenital ichthyosiform erythroderma. As ichthyosis is a cardinal feature of this condition, a Green rating on this panel is warranted.
Ichthyosis and erythrokeratoderma v3.25 ABHD5 Arina Puzriakova Gene: abhd5 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.24 ABHD5 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: ABHD5.
Tag Q1_24_NHS_review tag was added to gene: ABHD5.
Ichthyosis and erythrokeratoderma v3.24 ABHD5 Arina Puzriakova Publications for gene: ABHD5 were set to PubMed: 11590543
Intellectual disability v5.505 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome, 275630; CHANARIN-DORFMAN SYNDROME (CDS) to Chanarin-Dorfman syndrome, OMIM:275630
Palmoplantar keratodermas v3.25 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Neutral lipid storage disease to Chanarin-Dorfman syndrome, OMIM:275630
Ichthyosis and erythrokeratoderma v3.23 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome to Chanarin-Dorfman syndrome, OMIM:275630
Pulmonary fibrosis familial v1.7 ZCCHC8 Arina Puzriakova Publications for gene: ZCCHC8 were set to 31488579
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Vascular skin disorders v1.63 STAMBP Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: STAMBP.
Vascular skin disorders v1.63 STAMBP Arina Puzriakova Publications for gene: STAMBP were set to 23542699
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Classified gene: STAMBP as Amber List (moderate evidence)
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Multiple unrelated cases reported in the literature of biallelic variants in the STAMBP gene as the cause of microcephaly-capillary malformation syndrome (PMID: 21271646; 21548128; 21815250; 23542699; 25692795; 27531570; 29907875). Generalised capillary malformations on the skin are a cardinal feature of this condition and therefore inclusion of STAMBP on the panel is warranted.
Vascular skin disorders v1.62 STAMBP Arina Puzriakova Gene: stambp has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.504 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY CAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, OMIM:614261
Early onset or syndromic epilepsy v4.183 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Clefting v4.108 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY-CAPILLARY MALFORMATION SYNDROME; MICCAP to Microcephaly-capillary malformation syndrome, OMIM:614261
Fetal anomalies v3.145 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALYÐCAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, OMIM:614261
Severe microcephaly v4.66 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Vascular skin disorders v1.61 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from Microcephaly-capillary malformation syndrome, MIM# 614261 to Microcephaly-capillary malformation syndrome, OMIM:614261
Vascular skin disorders v1.60 PIK3R2 Arina Puzriakova Publications for gene: PIK3R2 were set to 22729224; 23745720; 28502725
Vascular skin disorders v1.59 PIK3R2 Arina Puzriakova commented on gene: PIK3R2
Vascular skin disorders v1.59 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1, OMIM:603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Intellectual disability v5.503 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Early onset or syndromic epilepsy v4.182 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Clefting v4.107 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Fetal anomalies v3.144 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Limb disorders v4.17 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387; Polydactyly to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Malformations of cortical development v4.24 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Segmental overgrowth disorders - Deep sequencing v3.17 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, 603387; MPPH1; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; Macrocephaly and Overgrowth Syndromes; Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Classified gene: FOXC2 as Green List (high evidence)
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Added comment: Comment on list classification: Inclusion of FOXC2 should be reviewed by the GMS specialist team due to conflicting reviews.

Lymphedema-distichiasis syndrome caused by heterozygous variants in this gene does not seem to fit the panel scope and is more appropriate for R136 Primary lymphoedema.
Vascular skin disorders v1.58 FOXC2 Arina Puzriakova Gene: foxc2 has been classified as Green List (High Evidence).
Vascular skin disorders v1.57 FOXC2 Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: FOXC2.
Tag Q1_24_expert_review tag was added to gene: FOXC2.
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Classified gene: FLT4 as Green List (high evidence)
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Added comment: Comment on list classification: Inclusion of FLT4 should be reviewed by the GMS specialist team due to conflicting reviews.

Primary lymphoedema caused by heterozygous variants in this gene does not fit the panel scope and is more appropriate for R136 Primary lymphoedema. Since 2002, there has only been one report of a somatic variant causing skin capillary haemangiomas (PMID:11807987). There has been no evidence of germline variants causing a similar phenotype.
Vascular skin disorders v1.57 FLT4 Arina Puzriakova Gene: flt4 has been classified as Green List (High Evidence).
Vascular skin disorders v1.56 FLT4 Arina Puzriakova Tag somatic tag was added to gene: FLT4.
Tag Q1_24_demote_red tag was added to gene: FLT4.
Tag Q1_24_expert_review tag was added to gene: FLT4.
Pulmonary fibrosis familial v1.6 ZCCHC8 Matthew Edwards reviewed gene: ZCCHC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 31488579, 38375433; Phenotypes: Pulmonary fibrosis (PF), telomere related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
CAKUT v1.175 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from unilateral kidney agenesis; bilateral kidney agenesis; vesicoureteral junction obstruction; vesicoureteral reflux; posterior urethral valve; genital malformation; increased kidney echogenicity to Neurooculorenal syndrome, OMIM:620305
CAKUT v1.174 ROBO1 Arina Puzriakova Classified gene: ROBO1 as Green List (high evidence)
CAKUT v1.174 ROBO1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Laura Claus (UMC). Rating Green as there is enough evidence to support the gene-disease association. Included on the R27 Paediatric disorders GMS panel via inclusion on the R29 Intellectual disability panel.

Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems which may be include a syndromic form of congenital anomalies of the kidney and urinary tract (CAKUT) (PMID: 35227688)
CAKUT v1.174 ROBO1 Arina Puzriakova Gene: robo1 has been classified as Green List (High Evidence).
Fetal anomalies v3.143 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28592524; 28485101; 30712880; 29194579; 35227688
Fetal anomalies v3.143 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28592524; 28485101; 30712880
Fetal anomalies v3.142 ROBO1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'monoallelic' to 'both mono- and biallelic' at the next GMS panel update.

Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems. However, some cases do present in utero with renal agenesis and structural brain abnormalities (PMID: 29194579; 35227688) indicating that the phenotype is relevant to this panel.
Fetal anomalies v3.142 ROBO1 Arina Puzriakova Mode of inheritance for gene: ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.141 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects; Neurooculorenal syndrome, OMIM:620305
Fetal anomalies v3.140 ROBO1 Arina Puzriakova Tag Q1_24_MOI tag was added to gene: ROBO1.
Intellectual disability v5.502 ROBO1 Arina Puzriakova Tag watchlist_moi tag was added to gene: ROBO1.
Albinism or congenital nystagmus v3.5 ROBO1 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (?Nystagmus 8, congenital, autosomal recessive, OMIM:257400). OMIM have only listed the publications already considered (PMID: 35348658) and therefore there is no new evidence to warrant further review.
Albinism or congenital nystagmus v3.5 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from nystagmus, congenital, autosomal recessive, MONDO:0009762 to ?Nystagmus 8, congenital, autosomal recessive, OMIM:257400
Pituitary hormone deficiency v3.11 ROBO1 Arina Puzriakova Tag watchlist tag was added to gene: ROBO1.
Pituitary hormone deficiency v3.11 ROBO1 Arina Puzriakova Publications for gene: ROBO1 were set to 28402530
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova changed review comment from: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore no new evidence to support promotion from amber to green.; to: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore there is no new evidence to support promotion from amber to green.
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova changed review comment from: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303); to: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303). OMIM have listed the all of the publications (PMID: 28402530; 31448886; 33270637) already previously considered by the GMS expert group and therefore no new evidence to support promotion from amber to green.
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with relevant phenotype in OMIM (Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303)
Pituitary hormone deficiency v3.10 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from pituitary stalk interruption syndrome, MONDO:0019828 to Pituitary hormone deficiency, combined or isolated, 8, OMIM:620303
Intellectual disability v5.502 CLEC16A Sarah Leigh edited their review of gene: CLEC16A: Added comment: Heterozygous CLEC16A variants have been identified as a genetic risk factor for several autoimmune disorders and for Parkinson disease (PMID: 37175930). PMID: 36538041 reports the neurological effect of homozygous terminating CLEC16A variants in two families. In family 1, the first child died at 5 months, he had progressive microcephaly, failure to thrive and cranial CT showed brain atrophy, dilatation of both central and peripheral liquor spaces, hypoplasia of the corpus callosum (no genetic testing was done), the third pregnancy was terminated (17 weeks of gestation) after prenatal ultrasound showed ventriculomegaly, agenesis of corpus callosum (no genetic testing was done), the fourth pregnancy was also terminated (22 weeks of gestation) as the prenatal ultrasound showed agenesis of corpus callosum. This fetus was homozygous for NM_001243403.1(CLEC16A):c.2062 + 5G > A, RT-PRC showed that this variant resulted in the deletion of exon 19 and a frame shift. Both parents and an unaffected sibling were heterozygous for this variant. In family 2, a single affected child was homozygous for NM_001243403.1(CLEC16A):c.-4_12del, p.Met1fs*. This child had progressive microcephaly, failure to thrive, severe global developmental delay, global brain atrophy and died at 6 years. There is no genetic data from the parents or unaffected siblings in Family 2. PMID: 37175930, also presents zebrafish experiments, where mutagenesis of
clec16a by CRISPR–Cas9 resulted in accumulated acidic/phagolysosome compartments, in neurons
and microglia, and dysregulated mitophagy. This was rescued by wild type CLEC16A, but not by the C-terminal truncated variant. The authors conclude that dysregulation of CLEC16A-mediated endosomal sorting is associated with neurodegeneration.; Changed rating: GREEN; Changed publications to: 36538041; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.502 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.502 CLEC16A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.502 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.501 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to PMID: 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.500 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.23 FHL1 Sarah Leigh reviewed gene: FHL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.499 ZFHX3 Sarah Leigh edited their review of gene: ZFHX3: Added comment: Personal communication from Nour Elkhateeb (Clinical Fellow in Genomics, Genomics England): we have data about 12 individuals with nonsense/frameshift/exon deletions in ZFHX3. Five of the variants are located in exon 9/10 or exon 9, which has been shown to harbour the highest density of pathogenic variants (PMID: 38412861). Eleven of these cases presented with developmental delay / intellectual disability and a range of other features, including dysmorphology, seizures and failure to thrive.; Changed publications to: 38412861
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.32 SMCHD1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: SMCHD1.
Tag Q1_24_MOI tag was added to gene: SMCHD1.
Tag Q1_24_NHS_review tag was added to gene: SMCHD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.32 SMCHD1 Sarah Leigh Phenotypes for gene: SMCHD1 were changed from Fascioscapulohumeral muscular dystrophy 2, digenic 158901; fascioscapulohumeral muscular dystrophy to Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM:158901; facioscapulohumeral muscular dystrophy 2, MONDO:0008031
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.31 SMCHD1 Sarah Leigh Publications for gene: SMCHD1 were set to
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh Deleted their comment
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh changed review comment from: In line with Ian Berry's (Leeds Genetics Laboratory) review, the mode of inheritance for SMCHD1 should be updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).; to: In line with the recommendations from Ian Berry (Leeds Genetics Laboratory), it is recommended that the mode of inheritance for this gene should be changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh edited their review of gene: SMCHD1: Added comment: In line with Ian Berry's (Leeds Genetics Laboratory) review, the mode of inheritance for SMCHD1 should be updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least 10 SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic (OMIM:158901)(PMID: 23143600; 24075187;31600781).; Changed publications to: 23143600, 24075187, 31600781
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Sarah Leigh edited their review of gene: SMCHD1: Added comment: In line with the recommendations from Ian Berry (Leeds Genetics Laboratory), it is recommended that the mode of inheritance for this gene should be changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. At least five SMCHD1 variants in unrelated cases have been associated with Fascioscapulohumeral muscular dystrophy 2, digenic, (OMIM:158901)(PMID: ).; Changed rating: GREEN; Changed publications to: 23143600; Changed phenotypes to: Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM:158901, facioscapulohumeral muscular dystrophy 2, MONDO:0008031; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v3.83 SPG7 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: SPG7.
Tag Q1_24_NHS_review tag was added to gene: SPG7.
Hereditary neuropathy or pain disorder v3.83 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; Changed rating: GREEN; Changed publications to: 30098094, 35637455, 35096021, 35243150, 22964162
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Dmitrijs Rots reviewed gene: ZFHX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.499 ZFHX3 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFHX3.
Tag Q1_24_NHS_review tag was added to gene: ZFHX3.
Intellectual disability v5.499 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Tag STR tag was added to gene: ZFHX3.
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Phenotypes for gene: ZFHX3 were changed from syndromic intellectual disability to Spinocerebellar ataxia 4, OMIM:600223; spinocerebellar ataxia type 4, MONDO:0010847
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.499
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Intellectual disability v5.499 ZFHX3 Sarah Leigh Classified gene: ZFHX3 as Amber List (moderate evidence)
Intellectual disability v5.499 ZFHX3 Sarah Leigh Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.103 ATP5E Sarah Leigh Tag new-gene-name was removed from gene: ATP5E.
Tag Q4_23_promote_green was removed from gene: ATP5E.
Tag Q4_23_NHS_review was removed from gene: ATP5E.
Tag watchlist tag was added to gene: ATP5E.
Tag Q1_24_promote_green tag was added to gene: ATP5E.
Tag Q1_24_NHS_review tag was added to gene: ATP5E.
Possible mitochondrial disorder - nuclear genes v3.103 ATP5E Sarah Leigh changed review comment from: PMID: 34954817 reports two further cases of OMIM: 614053 who are both homozygous for ATP5E (new gene name: ATP5F1E) variant c.35A>G, p.Tyr12Cys (rs387906929), previously reported in PubMed: 20566710. Personal communication with the lead author of PMID: 34954817, confirmed that none of these cases were related to one another and so represent independent occurrences of this variant.; to: PMID: 34954817 reports two further cases of OMIM: 614053 who are both homozygous for ATP5E (new gene name: ATP5F1E) variant c.35A>G, p.Tyr12Cys (rs387906929), previously reported in PubMed: 20566710. Personal communication with the lead author of PMID: 34954817, confirmed that none of these cases were related to one another and so represent independent occurrences of this variant. In addition, PMID: 34954817 reports significantly reduced ATPase amounts associated with the ATP5F1E variants.
Intellectual disability v5.498 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Hereditary neuropathy or pain disorder v3.83 XK Alexander Rossor commented on gene: XK: Should be included in R78 as now inlcudes many other complex phenotype genes that can present with neuropathy
Hereditary neuropathy or pain disorder v3.83 TYMP Alexander Rossor edited their review of gene: TYMP: Added comment: Can present with neuropathy and should be included in R78 panel; Changed publications to: 21933806
Hereditary neuropathy or pain disorder v3.83 SURF1 Alexander Rossor edited their review of gene: SURF1: Added comment: Should be included as R78 now includes complex phenotype genes; Changed publications to: 27475922, 12026244, 24027061
Hereditary neuropathy or pain disorder v3.83 SPTBN4 Alexander Rossor commented on gene: SPTBN4
Hereditary neuropathy or pain disorder v3.83 SLC25A19 Alexander Rossor edited their review of gene: SLC25A19: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 SCARB2 Alexander Rossor edited their review of gene: SCARB2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 21670406, 19597094
Hereditary neuropathy or pain disorder v3.83 SACS Alexander Rossor edited their review of gene: SACS: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 30460542
Hereditary neuropathy or pain disorder v3.83 POLR3A Alexander Rossor commented on gene: POLR3A: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PNPLA6 Alexander Rossor commented on gene: PNPLA6: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PMM2 Alexander Rossor edited their review of gene: PMM2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Neonatal onset, leukodystrophy, abnormal serum glycoproteins, mental retardation, hypotonia, ataxia, retinitis pigmentosa, seizures, slowly progressive neuropathy with SNCV, severe infections, hepatic insufficiency and cardiomyopathy.
Hereditary neuropathy or pain disorder v3.83 PLP1 Alexander Rossor edited their review of gene: PLP1: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 12601703
Hereditary neuropathy or pain disorder v3.83 PEX7 Alexander Rossor edited their review of gene: PEX7: Added comment: Should be included in R78 as can present with neuropathy and other complex disease are now include in R78; Changed publications to: 11493716
Hereditary neuropathy or pain disorder v3.83 PEX10 Alexander Rossor edited their review of gene: PEX10: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 27230853, 20695019
Hereditary neuropathy or pain disorder v3.83 PDYN Alexander Rossor commented on gene: PDYN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 NAGA Alexander Rossor commented on gene: NAGA: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MTTP Alexander Rossor commented on gene: MTTP: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MMACHC Alexander Rossor edited their review of gene: MMACHC: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Onset infancy to adulthood, thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high dose vitamin B12.
Hereditary neuropathy or pain disorder v3.83 LYST Alexander Rossor commented on gene: LYST: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 IARS2 Alexander Rossor edited their review of gene: IARS2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 25130867, 28328135, 30041933, 30419932
Hereditary neuropathy or pain disorder v3.83 GBA2 Alexander Rossor commented on gene: GBA2: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 BCKDHB Alexander Rossor edited their review of gene: BCKDHB: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 18855118, 11180212; Changed phenotypes to: Maple Syrup Urine Disease, Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 B4GALNT1 Alexander Rossor commented on gene: B4GALNT1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 APOA1 Alexander Rossor commented on gene: APOA1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor Deleted their comment
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor commented on gene: AP1S1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AGXT Alexander Rossor edited their review of gene: AGXT: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 4701948, 25363903
Hereditary neuropathy or pain disorder v3.83 AGTPBP1 Alexander Rossor commented on gene: AGTPBP1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 ABHD12 Alexander Rossor edited their review of gene: ABHD12: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 29571850, 20797687
Hereditary neuropathy or pain disorder v3.83 GAN Alexander Rossor commented on gene: GAN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 FXN Alexander Rossor edited their review of gene: FXN: Added comment: FA can present with a sensory neuropathy and should be included in the R78 panel. A missense may prompt testing for an expansion in the other allele.; Changed publications to: 20339857
Hereditary neuropathy or pain disorder v3.83 GALC Alexander Rossor edited their review of gene: GALC: Added comment: Can present with peripheral neuropathy and should be included in R78 panel; Changed publications to: 26840509; Changed phenotypes to: Krabbe. Spastic paraplegia, developmental delay, optic atrophy, adult onset has spastic paraplegia and sensory-motor axonal neuropathy with slow or normal conduction velocities, MRI shows leukodystrophy
Intellectual disability v5.497 SOX9 Tracy Lester reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.; to: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.23 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; optic atrophy, MONDO:0003608
Review for gene: SNF8 was set to AMBER
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Three of the patients (from two families) with the milder phenotype also have optic atrophy.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are only two unrelated patients reported with seizures and hence this gene should be rated amber with current evidence.
Early onset or syndromic epilepsy v4.181 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.180 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: SNF8 was set to AMBER
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Likely inborn error of metabolism v4.134 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia; Glycogen storage disease Ia, 232200; Glycogen storage disease type 1a, von Gierke (Glycogen storage disorders); Glycogen storage disease Ia; fasting intolerance with enlarged liver, renal tubular disease to Glycogen storage disease Ia, OMIM:232200
Mitochondrial disorders v4.167 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia to Glycogen storage disease Ia, OMIM:232200
Possible mitochondrial disorder - nuclear genes v3.103 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia, 232200 to Glycogen storage disease Ia, OMIM:232200
Undiagnosed metabolic disorders v1.615 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease type 1a, von Gierke (Glycogen storage disorders); fasting intolerance with enlarged liver, renal tubular disease; Glycogen storage disease Ia, 232200; Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia to Glycogen storage disease Ia, OMIM:232200
Glycogen storage disease v2.4 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from Glycogen storage disease Ia 232200 to Glycogen storage disease Ia, OMIM:232200
Ketotic hypoglycaemia v1.9 G6PC Arina Puzriakova Phenotypes for gene: G6PC were changed from fasting intolerance with enlarged liver, renal tubular disease; Glycogen storage disease Ia, 232200; Glycogen Storage Disease Type I; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen Storage Disease Ia to Glycogen storage disease Ia, OMIM:232200
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Classified gene: ATPAF1 as Red List (low evidence)
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex V deficiency v2.16 ATPAF1 Arina Puzriakova Gene: atpaf1 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Classified gene: ATPAF1 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.102 ATPAF1 Arina Puzriakova Gene: atpaf1 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Classified gene: COA4 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.19 COA4 Arina Puzriakova Gene: coa4 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Classified gene: COA4 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.101 COA4 Arina Puzriakova Gene: coa4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Classified gene: COX17 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.18 COX17 Arina Puzriakova Gene: cox17 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Classified gene: COX17 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.100 COX17 Arina Puzriakova Gene: cox17 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Classified gene: COX18 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.17 COX18 Arina Puzriakova Gene: cox18 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Classified gene: COX18 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.99 COX18 Arina Puzriakova Gene: cox18 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Classified gene: COX19 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.16 COX19 Arina Puzriakova Gene: cox19 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Classified gene: COX19 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.98 COX19 Arina Puzriakova Gene: cox19 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Classified gene: COX6B2 as Red List (low evidence)
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex IV deficiency v3.15 COX6B2 Arina Puzriakova Gene: cox6b2 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Classified gene: COX6B2 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.97 COX6B2 Arina Puzriakova Gene: cox6b2 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Classified gene: NDUFAF7 as Red List (low evidence)
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex I deficiency v3.8 NDUFAF7 Arina Puzriakova Gene: ndufaf7 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Classified gene: NDUFAF7 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.96 NDUFAF7 Arina Puzriakova Gene: ndufaf7 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Classified gene: SDHAF3 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.95 SDHAF3 Arina Puzriakova Gene: sdhaf3 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Classified gene: SDHAF3 as Red List (low evidence)
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex II deficiency v2.10 SDHAF3 Arina Puzriakova Gene: sdhaf3 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Classified gene: SDHAF4 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Possible mitochondrial disorder - nuclear genes v3.94 SDHAF4 Arina Puzriakova Gene: sdhaf4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Classified gene: SDHAF4 as Red List (low evidence)
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with human disease.
Mitochondrial disorder with complex II deficiency v2.9 SDHAF4 Arina Puzriakova Gene: sdhaf4 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Mitochondrial disorder with complex V deficiency v2.15 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Possible mitochondrial disorder - nuclear genes v3.93 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Classified gene: ATP5J2 as Red List (low evidence)
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Added comment: Comment on list classification: Demoting from Amber to Red as this gene has not been associated with a human disease.
Mitochondrial disorders v4.166 ATP5J2 Arina Puzriakova Gene: atp5j2 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism v4.133 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.92 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.91 CYCS Arina Puzriakova Publications for gene: CYCS were set to
Cytopenia - NOT Fanconi anaemia v3.27 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004; Thrombocytopenia to Thrombocytopenia 4, OMIM:612004
Bleeding and platelet disorders v3.8 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from 612004 Thrombocytopenia 4 to Thrombocytopenia 4, OMIM:612004
Cytopenias and congenital anaemias v1.118 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Inherited bleeding disorders v1.176 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4 to Thrombocytopenia 4, OMIM:612004
Mitochondrial disorders v4.165 CYCS Arina Puzriakova Phenotypes for gene: CYCS were changed from Thrombocytopenia 4, 612004 to Thrombocytopenia 4, OMIM:612004
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Classified gene: CYCS as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases to support a gene-disease association and given that in vitro studies of patient variants have shown functional defects in the mitochondrial respiratory chain, this gene can be promoted to Green status at the next GMS panel update.
Possible mitochondrial disorder - nuclear genes v3.90 CYCS Arina Puzriakova Gene: cycs has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.89 CYCS Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CYCS.
Possible mitochondrial disorder - nuclear genes v3.89 CYCS Arina Puzriakova commented on gene: CYCS
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CYCS.
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Classified gene: CYCS as Amber List (moderate evidence)
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases to support a gene-disease association and given that in vitro studies of patient variants have shown functional defects in the mitochondrial respiratory chain, this gene can be promoted to Green status at the next GMS panel update.
Mitochondrial disorders v4.164 CYCS Arina Puzriakova Gene: cycs has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.163 SPATA5 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: SPATA5.
Mitochondrial disorders v4.163 SPATA5 Arina Puzriakova Publications for gene: SPATA5 were set to 27246907; 29343804; 26299366; 28293831
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Classified gene: SPATA5 as Amber List (moderate evidence)
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases to promote this gene to Green at the next GMS panel update. Patients display a phenotype that resembles a mitochondrial disorder and functional studies on patient-derived cells have demonstrated an impact on mitochondrial function, further supporting inclusion of SPATA5 on this panel.
Mitochondrial disorders v4.162 SPATA5 Arina Puzriakova Gene: spata5 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.161 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Intellectual disability v5.497 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome, 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Early onset or syndromic epilepsy v4.179 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Monogenic hearing loss v4.26 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Fetal anomalies v3.140 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova changed review comment from: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.; to: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene is almost always in adulthood and poses risk of incidental findings, inclusion of PRNP on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Classified gene: PRNP as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Added comment: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Gene: prnp has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.73 PRNP Arina Puzriakova Phenotypes for gene: PRNP were changed from Creutzfeldt-Jakob disease 123400; Huntington disease-like 1 603218; Cerebral amyloid angiopathy, PRNP-related 137440; Gerstmann-Straussler disease 137440 to Cerebral amyloid angiopathy, PRNP-related, OMIM:137440; Huntington disease-like 1, OMIM:603218; Gerstmann-Straussler disease, OMIM:137440; Creutzfeldt-Jakob disease, OMIM:123400
Childhood onset dystonia, chorea or related movement disorder v3.72 PRNP Arina Puzriakova Publications for gene: PRNP were set to
Childhood onset dystonia, chorea or related movement disorder v3.71 PRNP Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: PRNP.
Tag Q1_24_expert_review tag was added to gene: PRNP.
Childhood onset dystonia, chorea or related movement disorder v3.71 PRNP Arina Puzriakova reviewed gene: PRNP: Rating: ; Mode of pathogenicity: None; Publications: 16831973; Phenotypes: ; Mode of inheritance: None
Sarcoma susceptibility v1.81 TP53 Arina Puzriakova Phenotypes for gene: TP53 were changed from Li-Fraumeni syndrome, OMIM:151623; Sarcoma, MONDO:0005089 to Li-Fraumeni syndrome, OMIM:151623; Solitary Fibrous Tumour; Sarcoma, MONDO:0005089
Sarcoma susceptibility v1.80 TP53 Arina Puzriakova Publications for gene: TP53 were set to 27050224; 28338660
Sarcoma susceptibility v1.79 TERT Arina Puzriakova Publications for gene: TERT were set to PMID: 31529158
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Classified gene: TERT as Red List (low evidence)
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Added comment: Comment on list classification: Although there is evidence to support that TERT promoter variants affect prognosis, they are not the driving alteration in SFT. Furthermore, this cancer panel is intended for germline susceptibility findings rather than somatic variants as described in the case of TERT.

Therefore, assigning a Red rating to the TERT gene on this panel.
Sarcoma susceptibility v1.78 TERT Arina Puzriakova Gene: tert has been classified as Red List (Low Evidence).
Sarcoma susceptibility v1.77 TERT Arina Puzriakova Tag promoter tag was added to gene: TERT.
Tag somatic tag was added to gene: TERT.
Sarcoma susceptibility v1.77 TERT Arina Puzriakova reviewed gene: TERT: Rating: ; Mode of pathogenicity: None; Publications: 24726063, 27562490, 29985536, 31529158, 31321477, 38392213, 38357190; Phenotypes: Solitary Fibrous Tumours; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases with intellectual disability and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SNF8.
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram changed review comment from: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature; to: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: SNF8 was set to GREEN
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Classified gene: EZR as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Not yet associated with any phenotype in OMIM or G2P. Rating Red as only a single case has been reported to date (PMID: 37301410). Patient had B-cell deficiency with progressive hypogammaglobulinemia. Additional cases required prior to promoting this gene.

A homozygous variant in EZR was also found in two siblings with a profound intellectual disability (PMID: 25504542) but no immunological manifestations were reported.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.195 EZR Arina Puzriakova Gene: ezr has been classified as Red List (Low Evidence).
Vascular skin disorders v1.56 CCBE1 Arina Puzriakova commented on gene: CCBE1
Vascular skin disorders v1.56 CCBE1 Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: CCBE1.
Tag Q1_24_expert_review tag was added to gene: CCBE1.
Intellectual disability v5.494 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME (HLLS) to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Primary lymphoedema v3.10 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; Hennekam Lymphangiectasia-Lymphedema Syndrome to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.179 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam-lymphangiectasia-lymphedema syndrome 1 235510 to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Fetal anomalies v3.139 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Primary immunodeficiency or monogenic inflammatory bowel disease v4.194 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome 1, 235510; Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features; Combined immunodeficiencies with associated or syndromic features to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510; Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features; Combined immunodeficiencies with associated or syndromic features
Fetal hydrops v1.64 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome 1, 235510; generalised lymphatic dysplasia; fetal hydrops to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510; generalised lymphatic dysplasia; fetal hydrops
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Classified gene: ALAS2 as Green List (high evidence)
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Added comment: Comment on list classification: Inclusion of ALAS2 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

Gain-of-function variants in the ALAS2 gene cause erythropoietic protoporphyria which is associated with acute phototoxic skin reactions following sunlight exposure. Although the origin of cutaneous manifestations is not directly vascular, this panel may provide a differential diagnosis. The FECH gene which also causes erythropoietic protoporphyria is also included on the panel.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.56 ALAS2 Arina Puzriakova Gene: alas2 has been classified as Green List (High Evidence).
Mitochondrial disorders v4.160 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1 300751; Protoporphyria, erythropoietic, X-linked 300752 to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Likely inborn error of metabolism v4.132 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity) to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Undiagnosed metabolic disorders v1.614 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity); X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); Erythropoietic protoporphyria, mild variant to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Iron metabolism disorders - NOT common HFE mutations v2.5 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked OMIM:300752; Anemia, sideroblastic, 1 OMIM:300751; X-linked erythropoietic protoporphyria MONDO:0010420; X-linked sideroblastic anemia 1 MONDO:0020721 to Anemia, sideroblastic, 1, OMIM:300751
Rare anaemia v3.8 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1, 300751; Anemia, sideroblastic, 1 300751; 300751 Sideroblastic anaemia 1; 300751 Anemia, sideroblastic, 1 to Anemia, sideroblastic, 1, OMIM:300751
Cytopenias and congenital anaemias v1.117 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, 1 300751 to Anemia, sideroblastic, 1, OMIM:300751
Cutaneous photosensitivity with a likely genetic cause v3.4 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked, 300752; Anemia, sideroblastic, X-linked, 300751 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Non-acute porphyrias v1.24 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Protoporphyria, erythropoietic, X-linked OMIM:300752; X-linked erythropoietic protoporphyria MONDO:0010420; Anemia, sideroblastic, X-linked OMIM:300751; X-linked sideroblastic anemia 1 MONDO:0020721 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Erythropoietic protoporphyria, mild variant v1.3 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Anemia, sideroblastic, X-linked, 300751; Protoporphyria, erythropoietic, X-linked, 300752 to Protoporphyria, erythropoietic, X-linked, OMIM:300752
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura and petechiae, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Additionally, previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicates that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.; to: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicating that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Classified gene: ADAMTS13 as Green List (high evidence)
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Added comment: Comment on list classification: Inclusion of ADAMTS13 was reassessed in light of the Red review by Zornitza Stark (Australian Genomics).

ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura which is predominantly characterised by haematological abnormalities. These defects can results in secondary dermatological features such as purpura, petechiae and vasculitis, indicates that this panel may be applicable in some cases and represents a differential diagnosis.

Previous discussions with the clinical specialist team indicated that this gene should be on the panel and therefore maintaining the current Green rating.
Vascular skin disorders v1.55 ADAMTS13 Arina Puzriakova Gene: adamts13 has been classified as Green List (High Evidence).
Cytopenia - NOT Fanconi anaemia v3.26 TUBA4A Achchuthan Shanmugasundram Phenotypes for gene: TUBA4A were changed from Thrombocytopenia to autosomal dominant macrothrombocytopenia, MONDO:0015372
Cytopenia - NOT Fanconi anaemia v3.25 TUBA4A Achchuthan Shanmugasundram Classified gene: TUBA4A as Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.25 TUBA4A Achchuthan Shanmugasundram Gene: tuba4a has been classified as Red List (Low Evidence).
Cytopenia - NOT Fanconi anaemia v3.24 TUBA4A Achchuthan Shanmugasundram reviewed gene: TUBA4A: Rating: RED; Mode of pathogenicity: None; Publications: 30760556; Phenotypes: autosomal dominant macrothrombocytopenia, MONDO:0015372; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 PTCRA Boaz Palterer gene: PTCRA was added
gene: PTCRA was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoimmunity; elevated TCRgamma/delta T cells; lymphopenia; low TREC
Penetrance for gene: PTCRA were set to Incomplete
Review for gene: PTCRA was set to GREEN
Added comment: Materna et al. identified 10 subjects from 7 kindreds with biallelic LOF PTCRA variants, moreover, the authors identified common hypomorphic alleles significantly associated with autoimmunity. Extensive in vivo, in vitro, and mouse functional validation and epidemiologic data.
Sources: Literature
Retinal disorders v4.81 SLC37A3 Siying Lin reviewed gene: SLC37A3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35486108; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.25 RIPOR2 Dmitrijs Rots reviewed gene: RIPOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32631815; Phenotypes: Adult-onset hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological segmental overgrowth v2.9 MAX James Poulter gene: MAX was added
gene: MAX was added to Neurological segmental overgrowth. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to PMID:38141607
Phenotypes for gene: MAX were set to Macrocephaly; Polydactyly; delayed ophthalmic development; autism
Penetrance for gene: MAX were set to Complete
Review for gene: MAX was set to GREEN
Added comment: Recurrent de novo variant (p.Arg60Gln) identified in 3 unrelated individuals. Pathogenicity supported by functional analysis.
Sources: Literature
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova commented on gene: DYNC2H1: - PMID: 22589734 (2012) - A 29 Mb deletion encompassing DYNC2H1 was found in one patient with syndromic hirschsprung disease which included moderate mental retardation, mild hydrocephalus, microcephaly, cardiomyopathy and congenital hypotonia. Other candidate genes in this region include CNTN5 and CARD17. Skeletal findings that are typical for DYNC2H1 are not reported.

Comment on publications: PMID: 22589734 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova Publications for gene: DYNC2H1 were set to
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: EXOC3L2.
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Classified gene: EXOC3L2 as Amber List (moderate evidence)
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Added comment: Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Neurological ciliopathies v3.18 EXOC3L2 Sarah Leigh Gene: exoc3l2 has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v3.17 EXOC3L2 Sarah Leigh Publications for gene: EXOC3L2 were set to 28749478; 27894351; 30327448
Neurological ciliopathies v3.16 EXOC3L2 Sarah Leigh reviewed gene: EXOC3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Neurological ciliopathies v3.16 EXOC3L2 Sarah Leigh Publications for gene: EXOC3L2 were set to 28749478; 27894351
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Classified gene: PCLO as Red List (low evidence)
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Added comment: Comment on list classification: There is not enough evidence for this gene to be Amber on this panel.
Early onset or syndromic epilepsy v4.178 PCLO Sarah Leigh Gene: pclo has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.177 ZNFX1 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.492
Early onset or syndromic epilepsy v4.177 ZNFX1 Sarah Leigh gene: ZNFX1 was added
gene: ZNFX1 was added to Early onset or syndromic epilepsy. Sources: Literature,Expert Review Amber
Q1_24_promote_green, Q1_24_NHS_review tags were added to gene: ZNFX1.
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33876776; 33872655
Phenotypes for gene: ZNFX1 were set to Immunodeficiency 91 and hyperinflammation, OMIM:619644; immunodeficiency 91 and hyperinflammation, MONDO:0030491
Intellectual disability v5.492 ZNFX1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZNFX1.
Tag Q1_24_NHS_review tag was added to gene: ZNFX1.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Classified gene: ZNFX1 as Amber List (moderate evidence)
Intellectual disability v5.492 ZNFX1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Gene: znfx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.491 ZNFX1 Sarah Leigh edited their review of gene: ZNFX1: Added comment: ZNFX1 variants are associated with Immunodeficiency 91 and hyperinflammation (OMIM:619644). Neurological involvement has been observed in at least 11 patients with OMIM:619644 (PMID:33876776;33872655). Of these, four had seizures, three had developmental regression, and one had developmental delay. The incidence of neurological involvement could be higher, but the mortality of affected children is high; in PMID:33872655 11/15 cases were deceased, with seven of these not surviving to 3 months of age.; Changed rating: GREEN
Intellectual disability v5.491 ZNFX1 Sarah Leigh gene: ZNFX1 was added
gene: ZNFX1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33876776; 33872655
Phenotypes for gene: ZNFX1 were set to Immunodeficiency 91 and hyperinflammation, OMIM:619644; immunodeficiency 91 and hyperinflammation, MONDO:0030491
Review for gene: ZNFX1 was set to AMBER
Added comment: Sources: Literature
Intellectual disability v5.490 SRPX2 Arina Puzriakova Phenotypes for gene: SRPX2 were changed from Rolandic epilepsy, mental retardation, and speech dyspraxia, 300643 -3; ROLANDIC EPILEPSY WITH SPEECH DYSPRAXIA AND MENTAL RETARDATION X-LINKED (RESDX) to ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, OMIM:300643
Early onset or syndromic epilepsy v4.176 SRPX2 Arina Puzriakova Phenotypes for gene: SRPX2 were changed from ?Rolandic epilepsy, mental retardation, and speech dyspraxia 300643 to ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, OMIM:300643
Intellectual disability v5.489 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Gene2Phenotype confirmed gene with ID HPO to Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.488 SMARCAL1 Arina Puzriakova Publications for gene: SMARCAL1 were set to
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova edited their review of gene: SMARCAL1: Changed phenotypes to: Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova reviewed gene: SMARCAL1: Rating: ; Mode of pathogenicity: None; Publications: 28796785, 20301550; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 SMARCAL1 Arina Puzriakova Added comment: Comment on phenotypes: Previous (overwritten) phenotypes: Schimke disease;Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure;Combined immunodeficiencies with associated or syndromic features
Primary immunodeficiency or monogenic inflammatory bowel disease v4.193 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900; Schimke disease; Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure; Combined immunodeficiencies with associated or syndromic features to Schimke immunoosseous dysplasia, OMIM:242900
Proteinuric renal disease v4.7 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia #242900 to Schimke immunoosseous dysplasia, OMIM:242900
Fetal anomalies v3.138 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from SCHIMKE IMMUNOOSSEOUS DYSPLASIA to Schimke immunoosseous dysplasia, OMIM:242900
Unexplained young onset end-stage renal disease v3.39 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Cytopenia - NOT Fanconi anaemia v3.24 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia, 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Skeletal dysplasia v4.53 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900; Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Unexplained kidney failure in young people v1.118 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Cerebral vascular malformations v3.11 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia 242900 to Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.487 ZFX Sarah Leigh changed review comment from: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.; to: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Intellectual disability v5.487 ZFX Sarah Leigh Phenotypes for gene: ZFX were changed from to X-linked neurodevelopmental disorder with recurrent facial gestalt
Intellectual disability v5.486 ZFX Sarah Leigh Publications for gene: ZFX were set to 26350204; 26740508
Intellectual disability v5.486 ZFX Sarah Leigh Classified gene: ZFX as Amber List (moderate evidence)
Intellectual disability v5.486 ZFX Sarah Leigh Added comment: Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Intellectual disability v5.486 ZFX Sarah Leigh Gene: zfx has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.485 ZFX Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFX.
Tag Q1_24_NHS_review tag was added to gene: ZFX.
Intellectual disability v5.485 ZFX Sarah Leigh reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: X-linked neurodevelopmental disorder with recurrent facial gestalt; 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 v5.485 AFF2 Arina Puzriakova Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type, 309548; FRAXE Syndrome; FRAGILE X-E MENTAL RETARDATION SYNDROME (FRAXE) to Intellectual developmental disorder, X-linked 109, OMIM:309548; Fragile XE syndrome (FRAXE)
Intellectual disability v5.484 PPP2R2B Arina Puzriakova Publications for gene: PPP2R2B were set to
Intellectual disability v5.483 PPP2R2B Arina Puzriakova edited their review of gene: PPP2R2B: Added comment: - PMID: 25356899 (2014) - missense variant (c.413G>C, p.Arg138Pro) in the PPP2R2B gene identified in a 7-year-old boy with moderate ID, intractable seizures and autistic features. Otherwise limited information provided.

Comment on publications: PMID: 25356899 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; Changed publications to: 25356899; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.483 NXF5 Arina Puzriakova Classified gene: NXF5 as Red List (low evidence)
Intellectual disability v5.483 NXF5 Arina Puzriakova Added comment: Comment on list classification: Maintaining Red rating as evidence linking this gene to ID is not definitive since patient variants have involved multiple genes and no cases of SNVs in the NXF5 gene have been reported.
Intellectual disability v5.483 NXF5 Arina Puzriakova Gene: nxf5 has been classified as Red List (Low Evidence).
Intellectual disability v5.482 NXF5 Arina Puzriakova Added comment: Comment on publications: PMID: 23675524 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.482 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050; 20096387
Intellectual disability v5.481 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050
Intellectual disability v5.480 NXF5 Arina Puzriakova reviewed gene: NXF5: Rating: ; Mode of pathogenicity: None; Publications: 11566096, 20096387, 22030050, 23675524; Phenotypes: ; Mode of inheritance: None
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram edited their review of gene: TUBA8: Changed publications to: 34704371
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram commented on gene: TUBA8: Six unrelated individuals were identified with TUBA8 missense variants in a large cohort of blood donors with mild thrombocytopenia and these individuals were generally asymptomatic and one had menorrhagia. There is also some functional data available.
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram Classified gene: TUBA8 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.23 TUBA8 Achchuthan Shanmugasundram Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.22 TUBA8 Achchuthan Shanmugasundram Phenotypes for gene: TUBA8 were changed from Macrothrombocytopenia, isolated, 2, autosomal dominant to Macrothrombocytopenia, isolated, 2, autosomal dominant, OMIM:619840
Cytopenia - NOT Fanconi anaemia v3.21 TUBA8 Achchuthan Shanmugasundram reviewed gene: TUBA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Macrothrombocytopenia, isolated, 2, autosomal dominant, OMIM:619840; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.137 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Severe microcephaly v4.65 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Primary immunodeficiency or monogenic inflammatory bowel disease v4.192 NHEJ1 Arina Puzriakova Added comment: Comment on phenotypes: Previous (overwritten) phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation;Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291;T-B- SCID;T-B+ SCID;Combined immunodeficiency;Cernunnos/XLF deficiency;Nl NK, radiation sensitive, microcephaly;Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.192 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation; Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291; T-B- SCID; T-B+ SCID; Combined immunodeficiency; Cernunnos/XLF deficiency; Nl NK, radiation sensitive, microcephaly; Immunodeficiencies affecting cellular and humoral immunity to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Intellectual disability v5.480 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Added comment: Comment on publications: New publication added - PMID:25902260. This paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques

Provides review of cases in literature and functional studies demonstrating brain expressed proteins that interact with the KIRREL3 using yeast two-hybrid screening supporting a link to neurological and cognitive disorders. They also show KIRREL3 localisation to the Golgi complex and synaptic secretary vesicles.
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 37605258; 33853164
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Classified gene: SMPD4 as Amber List (moderate evidence)
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are five individuals from three unrelated families with biallelic loss-of-function SMPD4 variants. They developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly. In addition, review of past reports showed 27% of patients had insulin-dependent diabetes.

This gene can therefore be promoted to green rating in the next GMS review.
Monogenic diabetes v2.57 SMPD4 Achchuthan Shanmugasundram Gene: smpd4 has been classified as Amber List (Moderate Evidence).
Monogenic diabetes v2.56 SMPD4 Achchuthan Shanmugasundram Phenotypes for gene: SMPD4 were changed from NDD, microcephaly and diabetes to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622; type 1 diabetes mellitus, MONDO:0005147
Monogenic diabetes v2.55 SMPD4 Achchuthan Shanmugasundram Publications for gene: SMPD4 were set to PMID: 36732302
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SMPD4.
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram edited their review of gene: SMPD4: Changed publications to: 36732302
Monogenic diabetes v2.54 SMPD4 Achchuthan Shanmugasundram reviewed gene: SMPD4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622, type 1 diabetes mellitus, MONDO:0005147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.478 KIF26B Arina Puzriakova Phenotypes for gene: KIF26B were changed from to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Intellectual disability v5.477 INTS1 Arina Puzriakova Phenotypes for gene: INTS1 were changed from Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, 618571; Hypotonia; Global developmental delay; Cataract; Abnormality of the skeletal system to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571
Intellectual disability v5.476 INTS1 Arina Puzriakova Publications for gene: INTS1 were set to 28542170; 30622326; 17544522
Optic neuropathy v4.22 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from Optic atrophy to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Intellectual disability v5.475 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Hereditary neuropathy or pain disorder v3.83 SPG7 Williams Kirsty reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: sensory neuropathy, motor neuropathy, lower-limb neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.474 EFNB1 Arina Puzriakova Classified gene: EFNB1 as Amber List (moderate evidence)
Intellectual disability v5.474 EFNB1 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber as a literature search did reveal evidence to suggest that some individuals may develop intellectual deficits. However, in most affected cases this was a mild presentation and there are more prominent and recognisable features observed in the general group of EFNB1-related cases which are more likely to inform diagnostic testing (e.g. craniosynostosis and clefting).
Intellectual disability v5.474 EFNB1 Arina Puzriakova Gene: efnb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.473 EFNB1 Arina Puzriakova Added comment: Comment on publications: PMID: 25679214 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.473 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to 23335590
Intellectual disability v5.472 EFNB1 Arina Puzriakova reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23335590, 25679214, 27650623, 31088393, 24520368; Phenotypes: Craniofrontonasal dysplasia, OMIM:304110; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v4.175 SLC5A6 Sarah Leigh Publications for gene: SLC5A6 were set to 27904971; 31392107; 31754459; 23104561; 29669219
Early onset or syndromic epilepsy v4.174 SLC5A6 Sarah Leigh Classified gene: SLC5A6 as Red List (low evidence)
Early onset or syndromic epilepsy v4.174 SLC5A6 Sarah Leigh Gene: slc5a6 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v4.173 SLC5A6 Sarah Leigh edited their review of gene: SLC5A6: Added comment: There is insufficient evidence of epilepsy associated with SLC5A6 variants (PMID: 35013551; 38036278; 38012394; 37391029; 31754459) for this gene to be rated as Amber on the Early onset or syndromic epilepsy, therefore it have been demoted to Red.; Changed rating: RED
Early onset or syndromic epilepsy v4.173 SLC5A6 Sarah Leigh Tag watchlist was removed from gene: SLC5A6.
Tag for-review was removed from gene: SLC5A6.
Tag to_be_confirmed_NHSE was removed from gene: SLC5A6.
Severe microcephaly v4.64 AKT3 Sarah Leigh reviewed gene: AKT3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v4.64 AKT3 Sarah Leigh Classified gene: AKT3 as Amber List (moderate evidence)
Severe microcephaly v4.64 AKT3 Sarah Leigh Gene: akt3 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.21 DNAJC30 Sarah Leigh Tag gene-checked was removed from gene: DNAJC30.
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Classified gene: ANK2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.173 ANK2 Achchuthan Shanmugasundram Gene: ank2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: ANK2.
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram changed review comment from: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2, of which seven patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature; to: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2 and with a complex neurodevelopmental disorder comprising intellectual disability, autism spectrum disorder and early-onset epilepsy. Seven of 12 patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature
Early onset or syndromic epilepsy v4.172 ANK2 Achchuthan Shanmugasundram gene: ANK2 was added
gene: ANK2 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 37195288
Phenotypes for gene: ANK2 were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: ANK2 was set to GREEN
Added comment: PMID:37195288 reported 12 individuals with heterozygous de novo LoF variants in ANK2, of which seven patients had early-onset epilepsy, with an onset of epilepsy before the age of 2 years. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Classified gene: MT-TL1 as Amber List (moderate evidence)
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Retinal disorders v4.81 MT-TL1 Achchuthan Shanmugasundram Gene: mt-tl1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.80 MT-TL1 Achchuthan Shanmugasundram Phenotypes for gene: MT-TL1 were changed from Retinitis pigmentosa to Retinal dystrophy, HP:0000556; Macular dystrophy, HP:0007754
Retinal disorders v4.79 MT-TL1 Achchuthan Shanmugasundram Publications for gene: MT-TL1 were set to
Retinal disorders v4.78 MT-TL1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: MT-TL1.
Tag Q1_24_NHS_review tag was added to gene: MT-TL1.
Retinal disorders v4.78 MT-TL1 Achchuthan Shanmugasundram reviewed gene: MT-TL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18332310, 23806424; Phenotypes: Retinal dystrophy, HP:0000556, Macular dystrophy, HP:0007754; Mode of inheritance: MITOCHONDRIAL
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Classified gene: TTC21B as Amber List (moderate evidence)
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, an additional case has been seen with the inherited retinal disease service at Moorfields Eye Hospital and was reported with a homozygous variant in 100k genome project.

As there are three cases reported with retinal dystrophy, this gene can be promoted to green rating in the next GMS review.
Retinal disorders v4.78 TTC21B Achchuthan Shanmugasundram Gene: ttc21b has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.77 TTC21B Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: TTC21B.
Tag Q1_24_NHS_review tag was added to gene: TTC21B.
Retinal disorders v4.77 TTC21B Achchuthan Shanmugasundram edited their review of gene: TTC21B: Changed rating: GREEN
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Classified gene: JAG1 as Amber List (moderate evidence)
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Retinal disorders v4.77 JAG1 Achchuthan Shanmugasundram Gene: jag1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.76 JAG1 Achchuthan Shanmugasundram Phenotypes for gene: JAG1 were changed from Alagille syndrome 1, OMIM:118450 to Alagille syndrome 1, OMIM:118450; exudative vitreoretinopathy, MONDO:0019516
Retinal disorders v4.75 JAG1 Achchuthan Shanmugasundram Publications for gene: JAG1 were set to
Retinal disorders v4.74 JAG1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: JAG1.
Tag Q1_24_NHS_review tag was added to gene: JAG1.
Retinal disorders v4.74 JAG1 Achchuthan Shanmugasundram reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31273345, 34185059; Phenotypes: Alagille syndrome 1, OMIM:118450, exudative vitreoretinopathy, MONDO:0019516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v4.16 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Craniofrontonasal syndrome, 304110 to Craniofrontonasal dysplasia, OMIM:304110
Skeletal dysplasia v4.52 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Craniofrontonasal dysplasia 304110 to Craniofrontonasal dysplasia, OMIM:304110
Fetal anomalies v3.136 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME to Craniofrontonasal dysplasia, OMIM:304110
Clefting v4.106 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME; CFNS to Craniofrontonasal dysplasia, OMIM:304110
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.178 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from 304110; Craniofrontonasal syndrome 304110 to Craniofrontonasal dysplasia, OMIM:304110
Intellectual disability v5.472 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Gene2Phenotype confirmed gene with ID HPO to Craniofrontonasal dysplasia, OMIM:304110
Intellectual disability v5.471 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to
Intellectual disability v5.470 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Skeletal ciliopathies v3.21 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Renal ciliopathies v3.4 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Rare multisystem ciliopathy disorders v1.169 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, 613091; Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Jeune syndrome; Short-rib thoracic dysplasia 3 with or without polydactyly to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Clefting v4.105 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from SHORT-RIB THORACIC DYSPLASIA 3 WITH OR WITHOUT POLYDACTYLY; SRTD3 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Unexplained young onset end-stage renal disease v3.38 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Thoracic and Cranioectodermal Dysplasia (Skeletal Ciliopathy) 15 Gene Panel; Short-rib thoracic dysplasia 3 with or without polydactyly, 613091; Short-rib thoracic dysplasia 3 with or without polydactyly; Jeune syndrome to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Skeletal dysplasia v4.51 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short rib polydactyly syndrome (SRPS) type 3 with or without polydactyly, 613091; Short rib polydactyly syndrome (SRPS) type 1/3 (Saldino-Noonan/Verma-Naumoff); Asphyxiating thoracic dystrophy 3, 613091Short rib-polydactyly syndrome, type III, 263510Short rib-polydactyly syndrome, type IIB, 615087 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Primary ciliary disorders v1.41 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from ciliopathies to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Ductal plate malformation v1.28 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly (613091) to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Limb disorders v4.15 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly 613091; Polydactyly to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Thoracic dystrophies v1.19 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Asphyxiating thoracic dystrophy 3, 613091Short rib-polydactyly syndrome, type III, 263510Short rib-polydactyly syndrome, type IIB, 615087 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, OMIM:160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, 160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449; 30055040; 34778950
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449
Intellectual disability v5.467 KCNA1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence)
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.465 KCNA1 Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30055040, 34778950; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of the three variants from PMID:30055040 with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic KCNA1 variants with epilepsy/ epileptic encephalopathy and hence this gene can be promoted to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.171 KCNA1 Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.170 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548; 31586945; 32316562; 34778950
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram edited their review of gene: KCNA1: Changed publications to: 30055040, 31586945, 32316562, 34778950
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain.

PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy.

PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG).

Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).
Early onset or syndromic epilepsy v4.169 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome 160120 to Episodic ataxia/ myokymia syndrome, OMIM:160120; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.168 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548
Early onset or syndromic epilepsy v4.167 KCNA1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.166 KCNA1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA1.
Tag Q1_24_NHS_review tag was added to gene: KCNA1.
Early onset or syndromic epilepsy v4.166 KCNA1 Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586945, 32316562, 34778950; Phenotypes: epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P v3.79 TAF4 Achchuthan Shanmugasundram Tag curated_removed was removed from gene: TAF4.
DDG2P v3.79 PBX1 Achchuthan Shanmugasundram Tag curated_removed was removed from gene: PBX1.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SAMD7.
Tag Q1_24_NHS_review tag was added to gene: SAMD7.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram changed review comment from: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SMAD7 has not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.; to: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SAMD7 have not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SMAD7 variants. Of these patients from four families had macular dystrophy with cone dysfunction, while patients from two families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SAMD7 variants. Of these, patients from four families had macular dystrophy with cone dysfunction, while patients from two other families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Classified gene: SAMD7 as Amber List (moderate evidence)
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there are six unrelated families identified with biallelic SMAD7 variants. Of these patients from four families had macular dystrophy with cone dysfunction, while patients from two families had macular dystrophy without cone dysfunction. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v4.74 SAMD7 Achchuthan Shanmugasundram Gene: samd7 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.73 SAMD7 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: As the evidence for this gene-disease association has been very recent, biallelic variants in SMAD7 has not yet been associated with retinal phenotypes either in OMIM or in Gene2Phenotype.
Retinal disorders v4.73 SAMD7 Achchuthan Shanmugasundram Phenotypes for gene: SAMD7 were changed from Macular dystrophy; cone dystrophy to macular dystrophy, retinal, MONDO:0031166; Congenital stationary cone dysfunction, HP:0030637
Retinal disorders v4.72 SAMD7 Achchuthan Shanmugasundram Publications for gene: SAMD7 were set to PMID: 38272031
Retinal disorders v4.71 SAMD7 Achchuthan Shanmugasundram reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38272031; Phenotypes: macular dystrophy, retinal, MONDO:0031166, Congenital stationary cone dysfunction, HP:0030637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.465 CTNND2 Arina Puzriakova commented on gene: CTNND2
Intellectual disability v5.465 CTNND2 Arina Puzriakova Phenotypes for gene: CTNND2 were changed from to CTNND2-related neurodevelopmental disorder
Intellectual disability v5.464 CTNND2 Arina Puzriakova Mode of inheritance for gene: CTNND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.463 CLIC2 Arina Puzriakova Tag disputed tag was added to gene: CLIC2.
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Tag Q1_22_NHS_review tag was added to gene: RNASEH2C.
Tag Q1_24_promote_green tag was added to gene: RNASEH2C.
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Tag Q1_24_promote_green tag was added to gene: RNASEH2B.
Tag Q1_24_NHS_review tag was added to gene: RNASEH2B.
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Deleted their comment
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh Tag Q1_24_promote_green tag was added to gene: RNASEH2A.
Tag Q1_24_NHS_review tag was added to gene: RNASEH2A.
Likely inborn error of metabolism v4.131 RNASEH2C Sarah Leigh edited their review of gene: RNASEH2C: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Likely inborn error of metabolism v4.131 RNASEH2B Sarah Leigh edited their review of gene: RNASEH2B: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Likely inborn error of metabolism v4.131 RNASEH2A Sarah Leigh edited their review of gene: RNASEH2A: Added comment: Saikat Santra (Birmingham Children's Hospital)(23 Jan 2024), has suggested that this gene should be green on this panel - R98.; Changed rating: GREEN
Palmoplantar keratodermas v3.24 PEX7 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: PEX7.
Palmoplantar keratodermas v3.24 PEX7 Sarah Leigh reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 MVK Sarah Leigh reviewed gene: MVK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 MVK Sarah Leigh Tag Q1_24_demote_red tag was added to gene: MVK.
Tag Q1_24_expert_review tag was added to gene: MVK.
Palmoplantar keratodermas v3.24 CLDN1 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: CLDN1.
Tag Q1_24_expert_review tag was added to gene: CLDN1.
Palmoplantar keratodermas v3.24 CLDN1 Sarah Leigh reviewed gene: CLDN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh edited their review of gene: CASP14: Changed rating: RED
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh reviewed gene: CASP14: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.24 CASP14 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: CASP14.
Tag Q1_24_expert_review tag was added to gene: CASP14.
Intellectual disability v5.463 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886 to Intellectual developmental disorder, X-linked syndromic 32, OMIM:300886
Hydrocephalus v4.4 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from ?Mental retardation, X-linked, syndromic 32, OMIM:300886 to Intellectual developmental disorder, X-linked syndromic 32, OMIM:300886
Intellectual disability v5.462 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Mental retardation, X-linked, syndromic 32, 300886 to Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova changed review comment from: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; to: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMIDs: 22511880 (2012) and 26177020 (2015) were identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020; 22511880
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova commented on gene: ARHGEF6: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088
Intellectual disability v5.459 ARHGEF6 Arina Puzriakova Phenotypes for gene: ARHGEF6 were changed from Mental retardation, X-linked 46, 300436; Mental Retardation, X-linked; MENTAL RETARDATION X-LINKED TYPE 46 to Intellectual developmental disorder, X-linked 46, OMIM:300436
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram changed review comment from: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature; to: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures. Microcephaly was severe in five children from four families.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Severe microcephaly v4.63 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Red List (low evidence)
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Severe microcephaly v4.62 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Red List (Low Evidence).
Severe microcephaly v4.61 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Early onset or syndromic epilepsy v4.166 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.165 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Severe microcephaly v4.61 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Early onset or syndromic epilepsy v4.165 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: ZNF335.
Tag Q1_24_expert_review tag was added to gene: ZNF335.
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Other than the one case that was reported by Chicago lab with ZNF335 heterozygous variant (c.2515_2518dupGCCA/ p.Thr840Serfs) and with microcephaly, encephalopathy and developmental delay, all other cases reported in the literature and ClinVar had biallelic variants in ZNF335. Hence, the MOI should be updated to "BIALLELIC, autosomal or pseudoautosomal" in the next GMS review.
Severe microcephaly v4.60 ZNF335 Achchuthan Shanmugasundram Mode of inheritance for gene: ZNF335 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v4.59 ZNF335 Achchuthan Shanmugasundram edited their review of gene: ZNF335: Changed rating: GREEN
Severe microcephaly v4.59 ZNF335 Achchuthan Shanmugasundram reviewed gene: ZNF335: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Classified gene: BAZ2B as Amber List (moderate evidence)
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Gene: baz2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from developmental delay, intellectual disability and autism spectrum disorder to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to 31999386; 37872713
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to 31999386; 37872713
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to PMID: 31999386
Intellectual disability v5.453 BAZ2B Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: BAZ2B.
Intellectual disability v5.453 BAZ2B Achchuthan Shanmugasundram reviewed gene: BAZ2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 37872713; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.71 JAG1 Siying Lin changed review comment from: Well-demarcated peripheral chorioretinal atrophic changes appear to be a not infrequent finding in patiets with Alagille syndrome, and have also been seen in within our inherited retinal dystrophy clinical cohort.; to: Well-demarcated peripheral chorioretinal atrophic changes appear to be a not infrequent finding in patiets with Alagille syndrome, and these retinal findings have also been seen in at least 2 unrelated patients with Alagille syndrome within our inherited retinal dystrophy clinical cohort
Retinal disorders v4.71 JAG1 Siying Lin reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34185059; Phenotypes: Retinal dystrophy, peripheral chorioretial atrophy, Alagille syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.71 TTC21B Siying Lin reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Retinal dystrophy, renal failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.71 MT-TL1 Siying Lin reviewed gene: MT-TL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18332310, 23806424; Phenotypes: retinal dystrophy, macular dystrophy, chorioretinal atrophy, MELAS; Mode of inheritance: MITOCHONDRIAL
Retinal disorders v4.71 ATXN7_CAG Siying Lin STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Retinal disorders. Sources: Literature
Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN7_CAG were set to PMID: 27632585,
Phenotypes for STR: ATXN7_CAG were set to Maculopaty; Cone-Rod Dystrophy
Review for STR: ATXN7_CAG was set to GREEN
Added comment: PMID: 27632585 (father of proband), this ARVO abstract ( https://iovs.arvojournals.org/article.aspx?articleid=2768575) and cases from our clinical cohort, demonstrate that affected individuals can present with a seemingly isolated maculopathy or cone-rod dystrophy that precedes the onset of neurological symptoms
Sources: Literature
Retinal disorders v4.71 SAMD7 Siying Lin gene: SAMD7 was added
gene: SAMD7 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to PMID: 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy; cone dystrophy
Penetrance for gene: SAMD7 were set to unknown
Mode of pathogenicity for gene: SAMD7 was set to Other
Review for gene: SAMD7 was set to GREEN
Added comment: 5 different variants identified in homozygosity in 6 families from varying ethnicities (Pakistani, African, Yemenite Jewish, Berber/Morocccan) segregating with disease. All affected individuals presented with macular dystrophy, a few had additional cone system involvement. Immunofluorescence studies show SAMD7 localisation to inner and outer nuclear layers of the human retina.
Sources: Literature
Early onset or syndromic epilepsy v4.164 KCNA1 Tracy Lester Deleted their comment
Early onset or syndromic epilepsy v4.164 KCNA1 Tracy Lester edited their review of gene: KCNA1: Added comment: There have been several recent reports that show de novo missense variants in specific regions of this gene are associated with epileptic encephalopathy, supported by functional studies, and gene now meets criteria to be green for this phenotype; Changed rating: GREEN; Changed publications to: 24578548, 3055040, 34778950; Changed phenotypes to: epilep
Intellectual disability v5.453 KCNA1 Tracy Lester reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055040, 34778950; Phenotypes: epileptic encephalopathy, ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 SMCHD1 Ian Berry reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Other; Current diagnostic: yes
Optic neuropathy v4.21 DNAJC30 Sarah Leigh commented on gene: DNAJC30
Optic neuropathy v4.21 DNAJC30 Sarah Leigh Phenotypes for gene: DNAJC30 were changed from Leber hereditary optic neuropathy, MONDO:0010788 to Leber-like hereditary optic neuropathy, autosomal recessive 1, MONDO:0958183; Leber-like hereditary optic neuropathy, autosomal recessive 1, OMIM:619382
Primary immunodeficiency or monogenic inflammatory bowel disease v4.191 LCP2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated cases reported now with biallelic LCP2 variants. Hence, this gene should be rated green in the next GMS review.; to: Comment on list classification: There are three unrelated cases reported with biallelic LCP2 variants and functional data available in support of the disease association. Hence, this gene should be rated green in the next GMS review.
Optic neuropathy v4.20 DNAJC30 Sarah Leigh Publications for gene: DNAJC30 were set to 33465056; 35091433
Primary immunodeficiency or monogenic inflammatory bowel disease v4.191 LCP2 Achchuthan Shanmugasundram Classified gene: LCP2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.191 LCP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases reported now with biallelic LCP2 variants. Hence, this gene should be rated green in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.191 LCP2 Achchuthan Shanmugasundram Gene: lcp2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.190 LCP2 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LCP2.
Tag Q1_24_NHS_review tag was added to gene: LCP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.190 LCP2 Achchuthan Shanmugasundram Phenotypes for gene: LCP2 were changed from SCID; combined T and B cell immunodeficiency; severe neutrophil defects; impaired platelet aggregation to ?Immunodeficiency 81, OMIM:619374
Primary immunodeficiency or monogenic inflammatory bowel disease v4.189 LCP2 Achchuthan Shanmugasundram Publications for gene: LCP2 were set to 33231617
Primary immunodeficiency or monogenic inflammatory bowel disease v4.188 LCP2 Achchuthan Shanmugasundram reviewed gene: LCP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33231617, 36474126, 37211057; Phenotypes: ?Immunodeficiency 81, OMIM:619374; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v4.104 LRRC32 Achchuthan Shanmugasundram Classified gene: LRRC32 as Amber List (moderate evidence)
Clefting v4.104 LRRC32 Achchuthan Shanmugasundram Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Clefting v4.103 LRRC32 Achchuthan Shanmugasundram gene: LRRC32 was added
gene: LRRC32 was added to Clefting. Sources: Literature
founder-effect tags were added to gene: LRRC32.
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112; 35656379
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074
Review for gene: LRRC32 was set to AMBER
Added comment: PMID:30976112 reported two unrelated families with global developmental delay, cleft palate, and proliferative retinopathy and they were identified with the same homozygous LRRC32 variant c.1630C>T/ p.Arg544Ter. This variant was suggested to be founder variant, as indicated by haplotype analysis.

PMID:35656379 reported a different homozygous LRRC32 variant (c.1354 G > A/ p.Glu452Lys) in a 15-year-old male with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy.

This gene has already been associated with relevant phenotypes in OMIM (MIM #619074), but not yet in Gene2Phenotype.
Sources: Literature
Retinal disorders v4.71 CNGA1 Arina Puzriakova Publications for gene: CNGA1 were set to
Structural eye disease v3.74 CNGA1 Arina Puzriakova Phenotypes for gene: CNGA1 were changed from Retinitis pigmentosa 49, 613756; Eye Disorders to Retinitis pigmentosa 49, OMIM:613756
Glaucoma (developmental) v1.45 CNGA1 Arina Puzriakova Mode of inheritance for gene: CNGA1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Glaucoma (developmental) v1.44 CNGA1 Arina Puzriakova Phenotypes for gene: CNGA1 were changed from Eye Disorders to Retinitis pigmentosa 49, OMIM:613756
Retinal disorders v4.70 CNGA1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'both mono- and biallelic' to 'biallelic' only at the next GMS panel update - could not find any evidence to suggest that heterozygous variants can lead to disease. Family members of patients that are heterozygous carriers are unaffected.
Retinal disorders v4.70 CNGA1 Arina Puzriakova Mode of inheritance for gene: CNGA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v4.69 CNGA1 Arina Puzriakova Tag Q1_24_MOI tag was added to gene: CNGA1.
Retinal disorders v4.69 CNGA1 Arina Puzriakova Phenotypes for gene: CNGA1 were changed from Retinitis pigmentosa 49, RP49 (AR); Eye Disorders; Retinitis pigmentosa; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa 49, 613756 to Retinitis pigmentosa 49, OMIM:613756
Retinal disorders v4.68 LRRC32 Achchuthan Shanmugasundram Classified gene: LRRC32 as Amber List (moderate evidence)
Retinal disorders v4.68 LRRC32 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are two different homozygous LRRC32 variants reported (c.1630C>T/ p.Arg544Ter & c.1354 G>A/ p.Glu452Lys) in three unrelated families, of which p.Arg544Ter variant reported in two families was suggested to be a founder variant as indicated by haplotype analysis. Hence, this gene should be rated amber with current evidence.
Retinal disorders v4.68 LRRC32 Achchuthan Shanmugasundram Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.67 LRRC32 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has already been associated with relevant phenotypes in OMIM (MIM #619074), but not yet in Gene2Phenotype.
Retinal disorders v4.67 LRRC32 Achchuthan Shanmugasundram Phenotypes for gene: LRRC32 were changed from Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074 to Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074
Retinal disorders v4.66 LRRC32 Achchuthan Shanmugasundram Phenotypes for gene: LRRC32 were changed from Cleft palate, proliferative retinopathy, and developmental delay to Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074
Retinal disorders v4.65 LRRC32 Achchuthan Shanmugasundram Publications for gene: LRRC32 were set to PMID: 30976112; PMID: 35656379
Retinal disorders v4.64 LRRC32 Achchuthan Shanmugasundram reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.64 LRRC32 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: LRRC32.
Intellectual disability v5.453 LRRC32 Achchuthan Shanmugasundram Classified gene: LRRC32 as Amber List (moderate evidence)
Intellectual disability v5.453 LRRC32 Achchuthan Shanmugasundram Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.452 LRRC32 Achchuthan Shanmugasundram Publications for gene: LRRC32 were set to 30976112
Intellectual disability v5.451 LRRC32 Achchuthan Shanmugasundram reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: 30976112, 35656379; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.64 MT-ATP6 Andrew Webster reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: Other; Publications: PubMed: 8095070, 33600551, 8476414; Phenotypes: retinal dystrophy, macular dystrophy, retinitis pigmentosa, neuropathy, ataxia.; Mode of inheritance: MITOCHONDRIAL
Likely inborn error of metabolism v4.131 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Likely inborn error of metabolism v4.131 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.89 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Possible mitochondrial disorder - nuclear genes v3.89 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.23 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Congenital muscular dystrophy v4.23 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.56 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.56 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.30 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Hereditary ataxia with onset in adulthood v4.30 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.29 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Mitochondrial disorders v4.159 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Mitochondrial disorders v4.159 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v4.158 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Fetal anomalies v3.135 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Fetal anomalies v3.135 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v3.134 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Possible mitochondrial disorder - nuclear genes v3.88 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Likely inborn error of metabolism v4.130 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v4.55 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Hereditary ataxia with onset in adulthood v4.29 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to
Mitochondrial disorders v4.158 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28554942; 28544275; 29339779
Likely inborn error of metabolism v4.130 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28554942; 28544275
Fetal anomalies v3.134 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 29339779; 28544275; 31604776; 31130378; 28554942
Possible mitochondrial disorder - nuclear genes v3.88 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28554942; 28544275; 29339779
Congenital muscular dystrophy v4.22 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28544275; 28554942; 31130378; 29339779; 37431817
Ataxia and cerebellar anomalies - narrow panel v4.55 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28554942; 28544275; 31604776; 31463572; 31130378; 30684668; 29339779
Retinal disorders v4.64 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 29339779; 28544275; 31604776; 31130378; 28554942
Congenital muscular dystrophy v4.21 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28544275; 28554942; 31130378; 29339779
Congenital muscular dystrophy v4.20 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Hereditary ataxia with onset in adulthood v4.28 MSTO1 Sarah Leigh reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.157 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.
There are no further reports of monoallelic Myopathy, mitochondrial, and ataxia (OMIM:617675).; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.133 MSTO1 Sarah Leigh reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.87 MSTO1 Sarah Leigh reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.129 MSTO1 Sarah Leigh reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v4.20 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.
There are no further reports of monoallelic Myopathy, mitochondrial, and ataxia (OMIM:617675).; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.54 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.
There are no further reports of monoallelic Myopathy, mitochondrial, and ataxia (OMIM:617675).; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.63 MSTO1 Sarah Leigh changed review comment from: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.; to: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.
There are no further reports of monoallelic Myopathy, mitochondrial, and ataxia (OMIM:617675).
Retinal disorders v4.63 MSTO1 Sarah Leigh reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: None; Publications: 28554942, 37431817; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.451 ACBD6 Jana Jezkova reviewed gene: ACBD6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37951597; Phenotypes: HP:0001263, HP:0001249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.10 ADA2 Sarah Leigh Publications for gene: ADA2 were set to 3471198, 25528372
Undiagnosed metabolic disorders v1.613 SLC6A19 Tracy Lester reviewed gene: SLC6A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Likely inborn error of metabolism v4.129 SLC6A19 Tracy Lester reviewed gene: SLC6A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Infantile enterocolitis & monogenic inflammatory bowel disease v1.42 PTEN Sarah Leigh edited their review of gene: PTEN: Added comment: Based on the review from Zornitza Stark, this gene has been demoted to amber on this panel.; Changed rating: AMBER
Infantile enterocolitis & monogenic inflammatory bowel disease v1.42 PTEN Sarah Leigh Classified gene: PTEN as Amber List (moderate evidence)
Infantile enterocolitis & monogenic inflammatory bowel disease v1.42 PTEN Sarah Leigh Gene: pten has been classified as Amber List (Moderate Evidence).
Infantile enterocolitis & monogenic inflammatory bowel disease v1.41 PTEN Sarah Leigh Publications for gene: PTEN were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.188 HSPA1L Zornitza Stark reviewed gene: HSPA1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inflammatory bowel disease, MONDO:0005265, HSPA1L-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital myopathy v4.36 VWA1 Eleanor Williams Classified gene: VWA1 as Amber List (moderate evidence)
Congenital myopathy v4.36 VWA1 Eleanor Williams Added comment: Comment on list classification: Promoting to amber, with a recommendation for consideration for a green rating following expert review as to whether the phenotype fits the scope of the congenital myopathy panel.
Congenital myopathy v4.36 VWA1 Eleanor Williams Gene: vwa1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.35 VWA1 Eleanor Williams gene: VWA1 was added
gene: VWA1 was added to Congenital myopathy. Sources: Literature
Q1_24_promote_green, Q1_24_expert_review tags were added to gene: VWA1.
Mode of inheritance for gene: VWA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA1 were set to 33459760
Phenotypes for gene: VWA1 were set to Neuronopathy, distal hereditary motor, autosomal recessive 7, OMIM:619216; neuronopathy, distal hereditary motor, autosomal recessive 7, MONDO:0030977
Added comment: In PMID: 33459760 Deschauer et al 2021 report 15 affected individuals from six families of German, Arabic, and Roma descent with biallelic loss of function variants in VWA1 and a neuromuscular phenotype. In 3 of the families the onset of symptoms was in childhood (ages 2-18yr in F3, ages 2-3yr in F4, and at school age in F5). Muscle biopsies of 3 individuals (F1-II.2, F2-II.1, and F5-II.1) revealed myopathic changes. A 10-bp tandem repeat is duplicated in one variant (p.Gly25Argfs*74]) and deleted in another variant (p.Gly21Alafs*12]). The duplication was found in 3 German families, homozygous in one and compound heterozygous in the other two.

PMID: 33559681 Pagnamenta et al 2021 report 17 individuals from 15 families with an autosomal-recessive, hereditary motor neuropathy and rare biallelic variants in VWA1. The p.(G25Rfs*74) 10-bp repeat expansion was observed in 14/15 families and was homozygous in 10/15. The authors state that the mean age of symptom recognition was 2.0 ± 1.4 years with tip-toe walking, foot deformities, Achilles tendon contractures, and recurrent hip and patellar dislocations.

Given the young age of onset in some patients and myopathy seen in biopsys this gene may be a candidate for green rating on this panel, subject to expert review.
Sources: Literature
Hereditary neuropathy or pain disorder v3.83 VWA1 Eleanor Williams Phenotypes for gene: VWA1 were changed from Neuropathy, hereditary motor, with myopathic features OMIM:619216; neuropathy, hereditary motor, with myopathic features MONDO:0030977 to Neuronopathy, distal hereditary motor, autosomal recessive 7, OMIM:619216; neuronopathy, distal hereditary motor, autosomal recessive 7, MONDO:0030977
Cystic kidney disease v4.24 OFD1 Nour Elkhateeb changed review comment from: OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected females. PMID: 10910455.; to: OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected females. PMID: 10910455.
Cystic kidney disease v4.24 OFD1 Nour Elkhateeb reviewed gene: OFD1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 10910455; Phenotypes: renal cysts; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.188 SIRT1 Achchuthan Shanmugasundram Phenotypes for gene: SIRT1 were changed from Type 1 diabetes; autoimmune disease to autoimmune disease, MONDO:0007179
Primary immunodeficiency or monogenic inflammatory bowel disease v4.187 SIRT1 Achchuthan Shanmugasundram Publications for gene: SIRT1 were set to PMID: 23473037
Primary immunodeficiency or monogenic inflammatory bowel disease v4.186 SIRT1 Achchuthan Shanmugasundram Classified gene: SIRT1 as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.186 SIRT1 Achchuthan Shanmugasundram Gene: sirt1 has been classified as Red List (Low Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.185 SIRT1 Achchuthan Shanmugasundram reviewed gene: SIRT1: Rating: RED; Mode of pathogenicity: None; Publications: 23473037; Phenotypes: autoimmune disease, MONDO:0007179; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.185 SCGN Achchuthan Shanmugasundram Classified gene: SCGN as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.185 SCGN Achchuthan Shanmugasundram Gene: scgn has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.184 SCGN Achchuthan Shanmugasundram Phenotypes for gene: SCGN were changed from ?early-onset ulcerative colitis to ulcerative colitis, MONDO:0005101
Primary immunodeficiency or monogenic inflammatory bowel disease v4.183 SCGN Achchuthan Shanmugasundram Publications for gene: SCGN were set to PMID: 31663849
Primary immunodeficiency or monogenic inflammatory bowel disease v4.182 SCGN Achchuthan Shanmugasundram changed review comment from: As reviewed by Hannah Knight, PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: As reviewed by Hannah Knight, PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.182 SCGN Achchuthan Shanmugasundram reviewed gene: SCGN: Rating: AMBER; Mode of pathogenicity: None; Publications: 31663849; Phenotypes: ulcerative colitis, MONDO:0005101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.46 ATXN2_CAG Jemeen Sreedharan reviewed STR: ATXN2_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20740007, 21479228, 21537950, 21562247; Phenotypes: amyotrophic lateral sclerosis, spinocerebellar ataxia 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.182 HSPA1L Achchuthan Shanmugasundram Classified gene: HSPA1L as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.182 HSPA1L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (seven unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.182 HSPA1L Achchuthan Shanmugasundram Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.181 HSPA1L Achchuthan Shanmugasundram Phenotypes for gene: HSPA1L were changed from Inflammatory bowel disease to inflammatory bowel disease, MONDO:0005265
Primary immunodeficiency or monogenic inflammatory bowel disease v4.180 HSPA1L Achchuthan Shanmugasundram Publications for gene: HSPA1L were set to PMID: 28126021
Primary immunodeficiency or monogenic inflammatory bowel disease v4.179 HSPA1L Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HSPA1L.
Tag Q1_24_NHS_review tag was added to gene: HSPA1L.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.179 HSPA1L Achchuthan Shanmugasundram reviewed gene: HSPA1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 28126021; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.179 CARD8 Achchuthan Shanmugasundram Publications for gene: CARD8 were set to 29408806
Primary immunodeficiency or monogenic inflammatory bowel disease v4.178 CARD8 Achchuthan Shanmugasundram Classified gene: CARD8 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.178 CARD8 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are two unrelated cases with heterozygous variants and Inflammatory bowel disease (Crohn disease). Hence, this gene should be rated amber with current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.178 CARD8 Achchuthan Shanmugasundram Gene: card8 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.177 CARD8 Achchuthan Shanmugasundram Phenotypes for gene: CARD8 were changed from ?Inflammatory bowel disease (Crohn disease) 30 to ?Inflammatory bowel disease (Crohn disease) 30, OMIM:619079
Primary immunodeficiency or monogenic inflammatory bowel disease v4.176 CARD8 Achchuthan Shanmugasundram Publications for gene: CARD8 were set to PMID: 29408806
Primary immunodeficiency or monogenic inflammatory bowel disease v4.175 CARD8 Achchuthan Shanmugasundram reviewed gene: CARD8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Inflammatory bowel disease (Crohn disease) 30, OMIM:619079; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.175 ANKZF1 Achchuthan Shanmugasundram Classified gene: ANKZF1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.175 ANKZF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: AS there is sufficient evidence for the association of monoallelic variants with infantile-onset inflammatory bowel disease, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.175 ANKZF1 Achchuthan Shanmugasundram Gene: ankzf1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.174 ANKZF1 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.

The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist_MOI' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.; to: Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.

The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist_moi' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.174 ANKZF1 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.

The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.; to: Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.

The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist_MOI' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.174 ANKZF1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: ANKZF1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.174 ANKZF1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are three unrelated cases reported with monoallelic ANKZF1 variants and infantile-onset inflammatory bowel disease. However, there are only two unrelated cases reported with biallelic variants, of which one has homozygous variant and other has compound heterozygous variants. The homozygous variant (p.Arg585Gln) is very common in gnomAD. Functional studies show that R585Q variant causes reduced ANKZF1 mRNA and protein expression and leads to reduced stress-induced mitochondrial translocation.

The MOI should therefore be set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" with the current evidence. In addition, 'watchlist' tag has been added to review any new evidence in support of the association of biallelic variants to inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.174 ANKZF1 Achchuthan Shanmugasundram Mode of inheritance for gene: ANKZF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.173 ANKZF1 Achchuthan Shanmugasundram Publications for gene: ANKZF1 were set to PMID: 28302725; PMID: 36857589
Primary immunodeficiency or monogenic inflammatory bowel disease v4.172 ANKZF1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.172 ANKZF1 Achchuthan Shanmugasundram Phenotypes for gene: ANKZF1 were changed from Inflammatory bowel disease to inflammatory bowel disease, MONDO:0005265
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 ANKZF1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: ANKZF1.
Tag Q1_24_NHS_review tag was added to gene: ANKZF1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 ANKZF1 Achchuthan Shanmugasundram reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 STAT4 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available (three unrelated cases and functional studies) for the association of this gene with disabling pansclerotic morphea of childhood (MIM #620443) and hence this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 STAT4 Achchuthan Shanmugasundram Classified gene: STAT4 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 STAT4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.171 STAT4 Achchuthan Shanmugasundram Gene: stat4 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.170 STAT4 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: STAT4.
Tag Q1_24_NHS_review tag was added to gene: STAT4.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.170 STAT4 Achchuthan Shanmugasundram changed review comment from: Comment on mode of pathogenicity: As reported in PMID:37256972, functional studies demonstrated that the variants caused a gain-of-function effect.; to: Comment on mode of pathogenicity: As reported in PMID:37256972, functional studies demonstrated that STAT4 variants caused a gain-of-function effect.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.170 STAT4 Achchuthan Shanmugasundram Mode of inheritance for gene: STAT4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.169 STAT4 Achchuthan Shanmugasundram Added comment: Comment on mode of pathogenicity: As reported in PMID:37256972, functional studies demonstrated that the variants caused a gain-of-function effect.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.169 STAT4 Achchuthan Shanmugasundram Mode of pathogenicity for gene: STAT4 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Primary immunodeficiency or monogenic inflammatory bowel disease v4.168 STAT4 Achchuthan Shanmugasundram Publications for gene: STAT4 were set to 29029192
Primary immunodeficiency or monogenic inflammatory bowel disease v4.167 STAT4 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIMs #612253 & #620443), but not in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.167 STAT4 Achchuthan Shanmugasundram Phenotypes for gene: STAT4 were changed from Paracoccidioidomycosis; Impaired IFN-γ Immunity; {Systemic lupus erythematosus, susceptibility to, 11}, 612253 to Disabling pansclerotic morphea of childhood, OMIM:620443; {Systemic lupus erythematosus, susceptibility to, 11}, OMIM:612253
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 STAT4 Achchuthan Shanmugasundram reviewed gene: STAT4: 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: 37256972; Phenotypes: Disabling pansclerotic morphea of childhood, OMIM:620443, {Systemic lupus erythematosus, susceptibility to, 11}, OMIM:612253; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v3.9 KCNQ1 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: KCNQ1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 LACC1 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: LACC1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 LACC1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LACC1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 LACC1 Achchuthan Shanmugasundram Classified gene: LACC1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 LACC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the association of this gene with juvenile arthritis and hence with this panel. So, this gene should be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.166 LACC1 Achchuthan Shanmugasundram Gene: lacc1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.165 LACC1 Achchuthan Shanmugasundram Publications for gene: LACC1 were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.164 LACC1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #618795), but not yet in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.164 LACC1 Achchuthan Shanmugasundram Phenotypes for gene: LACC1 were changed from Juvenile arthritis to Juvenile arthritis, OMIM:618795
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 LACC1 Achchuthan Shanmugasundram reviewed gene: LACC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25220867, 27881174, 29717096, 30872671; Phenotypes: Juvenile arthritis, OMIM:618795; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v3.9 KCNQ1 Achchuthan Shanmugasundram Publications for gene: KCNQ1 were set to 29097701
Pituitary hormone deficiency v3.8 KCNQ1 Achchuthan Shanmugasundram Classified gene: KCNQ1 as Amber List (moderate evidence)
Pituitary hormone deficiency v3.8 KCNQ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 that this gene has insufficient evidence for promotion to green rating.

There is an additional case reported with a previously identified variant (p.Pro369Leu) and growth hormone deficiency. Hence, I am tagging this gene for expert review by the NHSE to assess whether this evidence is sufficient for promotion to green rating.
Pituitary hormone deficiency v3.8 KCNQ1 Achchuthan Shanmugasundram Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram commented on gene: KCNQ1: As reviewed by Suzanne Page, PMID:36077086 reports two unrelated cases with KCNQ1 variants in addition to the cases previously reported in PMID: 29097701 with pituitary hormone deficiency and maternally inherited gingival fibromatosis. The single individual reported in PMID:36077086 with p.Pro369Leu variant had growth hormone deficiency and postnatal growth retardation in addition to coarse facial features and early-onset gingival overgrowth. However, three members of the other family with p.Val185Met variant had only coarse facial features and early-onset gingival overgrowth.
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36077086; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram Deleted their review
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 that this gene has insufficient evidence for promotion to green rating.

There is an additional case reported with a previously reported variant (p.Pro369Leu) and growth hormone deficiency. Hence, I am tagging this gene for expert review by the NHSE to assess whether this evidence is sufficient for promotion to green rating.; to: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 that this gene has insufficient evidence for promotion to green rating.

There is an additional case reported with a previously identified variant (p.Pro369Leu) and growth hormone deficiency. Hence, I am tagging this gene for expert review by the NHSE to assess whether this evidence is sufficient for promotion to green rating.
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 to have insufficient evidence for promotion to green rating. Hence, I am tagging this gene for expert review by the NHSE.; to: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 that this gene has insufficient evidence for promotion to green rating.

There is an additional case reported with a previously reported variant (p.Pro369Leu) and growth hormone deficiency. Hence, I am tagging this gene for expert review by the NHSE to assess whether this evidence is sufficient for promotion to green rating.
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 to have insufficient evidence for promotion to green rating. Hence, I am tagging this gene for expert review by the GLHs.; to: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 to have insufficient evidence for promotion to green rating. Hence, I am tagging this gene for expert review by the NHSE.
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram Classified gene: KCNQ1 as Amber List (moderate evidence)
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene was previously demoted from green to amber after being discussed and agreed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019 to have insufficient evidence for promotion to green rating. Hence, I am tagging this gene for expert review by the GLHs.
Pituitary hormone deficiency v3.7 KCNQ1 Achchuthan Shanmugasundram Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v3.6 KCNQ1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNQ1.
Tag Q1_24_expert_review tag was added to gene: KCNQ1.
Pituitary hormone deficiency v3.6 KCNQ1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v3.5 KCNQ1 Achchuthan Shanmugasundram reviewed gene: KCNQ1: 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: 36077086; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Nephrocalcinosis or nephrolithiasis v4.13 SLC26A1 Sarah Leigh reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Nephrocalcinosis or nephrolithiasis v4.13 SLC26A1 Sarah Leigh Classified gene: SLC26A1 as Red List (low evidence)
Nephrocalcinosis or nephrolithiasis v4.13 SLC26A1 Sarah Leigh Gene: slc26a1 has been classified as Red List (Low Evidence).
Nephrocalcinosis or nephrolithiasis v4.12 SLC26A1 Sarah Leigh Publications for gene: SLC26A1 were set to 27210743; 20160351; 30383413; 27125215; 24250268
Osteopetrosis v1.34 RASGRP2 Sarah Leigh Tag Q1_24_expert_review tag was added to gene: RASGRP2.
Osteopetrosis v1.34 RASGRP2 Sarah Leigh reviewed gene: RASGRP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Osteopetrosis v1.34 RASGRP2 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: RASGRP2.
Osteopetrosis v1.34 RASGRP2 Sarah Leigh Publications for gene: RASGRP2 were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 SIRT1 Hannah Knight gene: SIRT1 was added
gene: SIRT1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to PMID: 23473037
Phenotypes for gene: SIRT1 were set to Type 1 diabetes; autoimmune disease
Review for gene: SIRT1 was set to RED
Added comment: In PMID: 36634696 (2023) as one of the genes associated with monogenic IBD.
Just one previous report of it causing disease?
PMID: 23473037 (2013) - five individuals in one family found to have a missense SIRT1 variant (p.L107P). Four presented with type 1 diabetes, and one with ulcerative colitis
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 SCGN Hannah Knight gene: SCGN was added
gene: SCGN was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to PMID: 31663849
Phenotypes for gene: SCGN were set to ?early-onset ulcerative colitis
Review for gene: SCGN was set to RED
Added comment: Not linked to a phenotype in OMIM.
PMID: 31663849 (2019) reported three siblings with early onset UC, all with a homozygous missense variant in SCGN (p.Arg77His). Parents were both heterozygous. Some functional work done
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 LACC1 Hannah Knight gene: LACC1 was added
gene: LACC1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: LACC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LACC1 were set to Juvenile arthritis
Review for gene: LACC1 was set to GREEN
Added comment: PMID: 25220867 (2015) - in 13 patients and unaffected members of 5 consanguineous Saudi Arabian families with systemic juvenile idiopathic arthritis, a homozygous missense variant in LACC1 was identified (p.C284R). This segregated fully with disease, and haplotype analysis was consistent with a common founder for the 5 families. Systemic features were present including organomegaly, fevers and rashes
PMID: 27881174 (2016) - 2 Lebanese sisters with juvenile arthritis found to have a homozygous 1bp deletion in LACC1 (c.827delC). Present in heterozygosity in their unaffected consanguineous parents, but was not found in 2 unaffected sibs or in the ExAC database
PMID: 29717096 (2018) identified three different families with homozygous LACC1 variants (p.M1I, p.R414X, p.Ile330del)
PMID: 30872671 (2019) - three affected siblings with a homozygous variant (p.Cys43TyrfsTer6)
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 HSPA1L Hannah Knight gene: HSPA1L was added
gene: HSPA1L was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to PMID: 28126021
Phenotypes for gene: HSPA1L were set to Inflammatory bowel disease
Review for gene: HSPA1L was set to AMBER
Added comment: PMID: 28126021 (2017) identified a heterozygous de novo variant (c.830C > T; p.Ser277Leu) in HSPA1L in a patient with IBD + some in vitro testing which supported pathogenicity
Then identified five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) in six patients from their IBD cohort
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 CARD8 Hannah Knight gene: CARD8 was added
gene: CARD8 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: CARD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CARD8 were set to PMID: 29408806
Phenotypes for gene: CARD8 were set to ?Inflammatory bowel disease (Crohn disease) 30
Review for gene: CARD8 was set to AMBER
Added comment: On OMIM as ?association.
PMID: 29408806 (2018) identified a heterozygous missense CARD8 variant (V44I) in a boy, his mother, and his maternal aunt with Crohn disease. Not found in the proband's unaffected father. Functional analysis suggested a dominant-negative effect.

PMID: 37724393 (2023) identified a CARD8 VUS in a paediatric patient with IBD and arthritis. Can't see full paper however
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 ANKZF1 Hannah Knight gene: ANKZF1 was added
gene: ANKZF1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: ANKZF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ANKZF1 were set to PMID: 28302725; PMID: 36857589
Phenotypes for gene: ANKZF1 were set to Inflammatory bowel disease
Review for gene: ANKZF1 was set to AMBER
Added comment: PMID: 28302725 (2017) identified two infantile-onset IBD patients with biallelic ANKZF1 variants + some functional work:
One homozygous for R585Q - although this variant is very common in gnomAD
One compound heterozygous for E152K and V32_Q87del
Also two patients with one heterozygous variants

PMID: 36857589 (2023) also identified a de novo variant (p.Leu415Val) in a young patient with IBD
Sources: Literature
Early onset or syndromic epilepsy v4.164 MADD Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v4.164 MADD Sarah Leigh commented on gene: MADD: Apnoea is a feature of DEEAH syndrome (OMIM:619004) and Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (OMIM:619005), both of which are caused by biallelic MADD variants (PMID: 32761064).
Possible mitochondrial disorder - nuclear genes v3.87 BTD Mohamed Nassr commented on gene: BTD
Intellectual disability v5.451 MADD Sarah Leigh Phenotypes for gene: MADD were changed from Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, 619005; DEEAH syndrome, 619004 to DEEAH syndrome, OMIM:619004; deeah syndrome, MONDO:0033561: Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, OMIM:619005; neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, MONDO:0033562
Early onset or syndromic epilepsy v4.164 MADD Sarah Leigh Phenotypes for gene: MADD were changed from Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, 619005; DEEAH syndrome, 619004 to DEEAH syndrome, OMIM:619004; deeah syndrome, MONDO:0033561: Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, OMIM:619005; neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, MONDO:0033562
Intellectual disability v5.450 DHX37 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variant have not been associated with intellectual disability.; to: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variants have not been associated with intellectual disability.
Ehlers Danlos syndrome with a likely monogenic cause v3.11 EFEMP1 Sarah Leigh edited their review of gene: EFEMP1: Added comment: Monoallelic EFEMP1 variants have been associated with Doyne honeycomb degeneration of retina (OMIM:126600). PMIDs 31792352; 32006683; 33807164 report four recessive EFEMP1 variants in three cases with a pronounced connective tissue disorder. PMID: 31792352 also describes a Efemp1 knockout mouse model, with a phenotype that matches the human cases.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause v3.11 EFEMP1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: EFEMP1.
Ehlers Danlos syndrome with a likely monogenic cause v3.11 EFEMP1 Sarah Leigh Classified gene: EFEMP1 as Amber List (moderate evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.11 EFEMP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ehlers Danlos syndrome with a likely monogenic cause v3.11 EFEMP1 Sarah Leigh Gene: efemp1 has been classified as Amber List (Moderate Evidence).
Ehlers Danlos syndrome with a likely monogenic cause v3.10 EFEMP1 Sarah Leigh Publications for gene: EFEMP1 were set to 32006683; 31792352
Pituitary hormone deficiency v3.5 KCNQ1 Suzanne Page changed review comment from: Bauer et al 2022 PMID: 36077086 - Identified a single individual with the KCNQ1 variant P369L and three family members with the V185M variant. All had gingival overgrowth. Tommiska et al 2017 (PMID: 29097701) have already identified 3 families affected with pituitary hormone deficiency and maternally inherited gingival fibromatosis. Bauer et al showed that all 3 variants impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component.; to: Bauer et al 2022 PMID: 36077086 - Identified a single individual with the KCNQ1 variant P369L and three family members with the V185M variant. All had gingival overgrowth. Tommiska et al 2017 (PMID: 29097701) have already identified 3 families affected with pituitary hormone deficiency and maternally inherited gingival fibromatosis. Bauer et al showed that all 3 variants impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component. They suggest that the impaired Ca2+ sensitivity of the KCNQ1 mutant channels R116L, V185M and P369L is causally related to their gain-of-function when forming heteromers with KCNE2.
Pituitary hormone deficiency v3.5 KCNQ1 Suzanne Page reviewed gene: KCNQ1: 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: 36077086; Phenotypes: Gingival overgrowth, with or without postnatal growth retardation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.163 SLC5A6 Helen Lord edited their review of gene: SLC5A6: Added comment: PMID 35013551 Holling et al, 2022 - reporting 5 individuals from 3 families with motor neuropathies. Hom variant c.1285A>G p.(Ser429Gly) in 3 aff siblings and a simplex patient; and a third family where proband had a mat inherited c.280C>T p.(Arg94*) and a pat inherited c.485A>G p.(Tyr162Cys). in silico tools suggest missense variants affect function. No mention of epilepsy in any of these individuals.

PMID 38036278 Hsieh et al 2023 - Family with compound het SLC5A6 missense variants reported. No mention of epilepsy in affected individuals.

PMID 38012394 Utsuno et al 2024 - 3 sibs from a Japanese family with periventricular brain cysts and motor developmental delay - all compund het for SLC5A6 missense variants - no mention of epilepsy/seizure in any of these sibs.

PMID 37391029 Montomoli et al 2023 - 3 members of the same family - Patient 2 had a generalised tonic-clonic seizre and EEG showed sharp waves in left centro-temporal region. No mention of seizures at follow up at 24 years of age, and no mention prior to this seizure but lots of other clinical features. All affecteds had a hom fs SLC5A6 variant, parents het. Table summarising cases showed epilepsy in 2/13 case - patient 2 in this paper and the Byrne et al paper.

PMID 31754459 Byrne et al - see review 31/01/2021.

No new evidence to support a stronger link with SLC5A6 and an epilepsy phenotype.; Changed publications to: 35013551, 38036278, 38012394, 37391029, 31754459, 27904971
Early onset or syndromic epilepsy v4.163 CACNB4 Helen Lord edited their review of gene: CACNB4: Added comment: PMID 35813387 - Naseer et al, 2022: WES i one family and targeted sequencing of SCN1A and CACNB4 in 25 sporadic epilepsy patients. 3 different unrelated patients found to have the c.78_79insG variant in CACNB4. Do mention that tecently het CACNB4 mutations are not linked with epilepsy [Heyne et al 2019] and that het mutated animal model did not show any tyoe of deformities [Coba et al, 2012].

Also PMID32176688 - see previous occurence where identifed homozygously.; Changed rating: AMBER; Changed publications to: 35813387
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 STAT4 Hannah Knight reviewed gene: STAT4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37256972; Phenotypes: Disabling pansclerotic morphea of childhood; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.450 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from None to None
Intellectual disability v5.450 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from Other to None
Intellectual disability v5.449 ABCC9 Tracy Lester edited their review of gene: ABCC9: Added comment: This gene is currently green for monoallelic inheritance but the associated review relates to cases with biallelic inheritance. The MOI for this gene should be amended to biallelic only. Monoallelic variants are associated with Cantu syndrome which is not primarily an ID disorder or DCM.; Changed rating: GREEN
Intellectual disability v5.449 DHX37 Sarah Leigh Tag Q1_24_MOI tag was added to gene: DHX37.
Tag Q1_24_NHS_review tag was added to gene: DHX37.
Intellectual disability v5.449 DHX37 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variant have not been associated with intellectual disability.
Intellectual disability v5.449 DHX37 Sarah Leigh Mode of inheritance for gene: DHX37 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.448 DHX37 Sarah Leigh edited their review of gene: DHX37: Added comment: Biallelic DHX37 variants have been associated with Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies (OMIM:618731). Five DHX37 variants have been reported in three unrelated cases of OMIM:618731. Zebra fish models, support the role of DHX37 variants in aberrant behaviors (PMID: 24027265); Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.448 ABCC9 Sarah Leigh Added comment: Comment on mode of pathogenicity: Loss of function variants do cause the phenotype of Intellectual disability and myopathy syndrome (OMIM:619719) , which is relevant to this panel.
Intellectual disability v5.448 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from to Other
Intellectual disability v5.447 DHX37 Sarah Leigh Publications for gene: DHX37 were set to 26539891; 31256877
Intellectual disability v5.446 ABCC9 Sarah Leigh Tag watchlist_moi was removed from gene: ABCC9.
Tag Q1_24_MOI tag was added to gene: ABCC9.
Tag Q1_24_NHS_review tag was added to gene: ABCC9.
Intellectual disability v5.446 ABCC9 Sarah Leigh Phenotypes for gene: ABCC9 were changed from Cardiomyopathy, dilated, 10, 608569; Atrial fibrillation, familial, 12, 614050; Hypertrichotic osteochondrodysplasia, 239850; CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA to Intellectual disability and myopathy syndrome, OMIM:619719; intellectual disability and myopathy syndrome, MONDO:0859224
Intellectual disability v5.445 ABCC9 Sarah Leigh changed review comment from: Seven homozygous loss of function ABCC9 variants have been reported in seven unrelated cases of Intellectual disability and myopathy syndrome (OMIM:619719)(PMID: 31575858; 38217872). In vivo studies of abcc9 LoF in zebrafish, revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility.(PMID: 38217872).; to: Seven homozygous loss of function ABCC9 variants have been reported in seven unrelated cases of Intellectual disability and myopathy syndrome (OMIM:619719)(PMID: 31575858; 38217872). In vivo studies of abcc9 LoF in zebrafish, revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility.(PMID: 38217872). Heterozygous parents of the cases, did not show a consistent phenotype, although intrauterine death was reported in two families (PMID: 38217872). In family 4 the fetus was homozygous for c.1858C>T, p.(Arg620Ter) and in family 8 the parents were both heterozygous for c.2140_2141del, p.(Leu714SerfsTer7), but analysis of the fetus was not possible.
Intellectual disability v5.445 ABCC9 Sarah Leigh reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 38217872; Phenotypes: Intellectual disability and myopathy syndrome, OMIM:619719, intellectual disability and myopathy syndrome, MONDO:0859224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.445 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to 25529582; 24896178; 31575858; 38217872
Intellectual disability v5.444 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to 25529582; 24896178; 31575858
Intellectual disability v5.443 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to
Early onset or syndromic epilepsy v4.163 MADD Sarah Leigh edited their review of gene: MADD: Added comment: Comments from Karen Stals (Royal Devon and Exeter Hospital), 4 Dec 2023: Apnoea a presenting feature in 13/14 patients with MADD-related disorder with biallelic MADD variants in Schneeberger et al 2020 PMID: 32761064. Identified biallelic variants in this gene in a patient with a consistent phenotype.; Changed rating: GREEN; Changed publications to: 32761064
Intellectual disability v5.442 MADD Sarah Leigh edited their review of gene: MADD: Added comment: Comments from Karen Stals (Royal Devon and Exeter Hospital), 4 Dec 2023: Apnoea a presenting feature in 13/14 patients with MADD-related disorder with biallelic MADD variants in Schneeberger et al 2020 PMID: 32761064. Identified biallelic variants in this gene in a patient with a consistent phenotype.; Changed rating: GREEN; Changed publications to: 32761064
Paediatric or syndromic cardiomyopathy v3.43 CASZ1 Ludmila Volozonoka gene: CASZ1 was added
gene: CASZ1 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to 36293425; 31268246; 28099117; 27693370; 37509718
Phenotypes for gene: CASZ1 were set to Pediatric Dilated Cardiomyopathy; Pediatric LVNC
Review for gene: CASZ1 was set to GREEN
Added comment: Loss of Function variants described in patients with pediatric dilated cardiomyopathy, pediatric LVNC (36293425; 31268246). Our laboratory identified the LOF variant in a pediatric patient with LVNC.

The limited implication in congenital ventricular septal defect (27693370) - authors identified a missense variant.

Review article on CASZ1 (37509718).
Sources: Literature
Left Ventricular Noncompaction Cardiomyopathy v1.4 CASZ1 Ludmila Volozonoka gene: CASZ1 was added
gene: CASZ1 was added to Left Ventricular Noncompaction Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to 36293425; 31268246; 28099117; 27693370; 37509718
Phenotypes for gene: CASZ1 were set to Pediatric Cardiomyopathy; Pediatric LVNC
Review for gene: CASZ1 was set to GREEN
Added comment: Loss of Function variants described in patients with pediatric dilated cardiomyopathy, pediatric LVNC (36293425; 31268246), as well as in adults (28099117).
The limited implication in congenital ventricular septal defect (27693370) - authors identified a missense variant.
Review article on CASZ1 (37509718).
Our laboratory identified LOF variant in a pediatric patient with LVNC.
Sources: Literature
Retinal disorders v4.63 UBAP1L Achchuthan Shanmugasundram Classified gene: UBAP1L as Amber List (moderate evidence)
Retinal disorders v4.63 UBAP1L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are five unrelated cases with four different UBAP1L variants reported with either Rod-cone dystrophy, cone-rod dystrophy or retinitis pigmentosa. Hence, this gene should be promoted to green rating in the next GMS review.
Retinal disorders v4.63 UBAP1L Achchuthan Shanmugasundram Gene: ubap1l has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.62 UBAP1L Achchuthan Shanmugasundram Phenotypes for gene: UBAP1L were changed from Retinitis pigmentosa to Rod-cone dystrophy, HP:0000510; cone-rod dystrophy, MONDO:0015993; retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.61 UBAP1L Achchuthan Shanmugasundram Publications for gene: UBAP1L were set to 28041643
Retinal disorders v4.60 UBAP1L Achchuthan Shanmugasundram Mode of inheritance for gene: UBAP1L was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.59 UBAP1L Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: UBAP1L.
Tag Q1_24_NHS_review tag was added to gene: UBAP1L.
Retinal disorders v4.59 UBAP1L Achchuthan Shanmugasundram edited their review of gene: UBAP1L: Changed phenotypes to: Rod-cone dystrophy, HP:0000510, cone-rod dystrophy, MONDO:0015993, retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.59 UBAP1L Achchuthan Shanmugasundram reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rod-cone dystrophy, HP:0000510, cone-rod dystrophy, MONDO:0015993; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.59 RAX2 Achchuthan Shanmugasundram Publications for gene: RAX2 were set to
Retinal disorders v4.58 RAX2 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence available for the association of biallelic RAX2 variants with retinitis pigmentosa. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.; to: Comment on mode of inheritance: There is sufficient evidence available for the association of biallelic RAX2 variants with retinitis pigmentosa. Hence, the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Retinal disorders v4.58 RAX2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of biallelic RAX2 variants with retinitis pigmentosa. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Retinal disorders v4.58 RAX2 Achchuthan Shanmugasundram Mode of inheritance for gene: RAX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v4.57 RAX2 Achchuthan Shanmugasundram Phenotypes for gene: RAX2 were changed from Achromatopsia, Cone, and Cone-rod Dystrophy; Macular Degeneration; Eye Disorders; Cone-Rod Dystrophy, Dominant; Cone-rod dystrophy 11 to Cone-rod dystrophy 11, OMIM:610381; Retinitis pigmentosa 95, OMIM:620102; ?Macular degeneration, age-related, 6, OMIM:613757
Retinal disorders v4.56 RAX2 Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: RAX2.
Retinal disorders v4.56 RAX2 Achchuthan Shanmugasundram reviewed gene: RAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30377383, 30607024; Phenotypes: Cone-rod dystrophy 11, OMIM:610381, Retinitis pigmentosa 95, OMIM:620102, ?Macular degeneration, age-related, 6, OMIM:613757; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.442 KIRREL3 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: KIRREL3.
Intellectual disability v5.442 KIRREL3 Sarah Leigh Phenotypes for gene: KIRREL3 were changed from Mental retardation, autosomal dominant 4, 612581; MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 4 (MRD4) to Intellectual developmental disorder, autosomal dominant 4, OMIM:612581; intellectual disability, autosomal dominant 4, MONDO:0012947
Intellectual disability v5.441 KIRREL3 Sarah Leigh changed review comment from: At least 15 missense KIRREL3 variants have been reported in 17 unrelated cases with a neurodevelopmental disorder, that includes intellectual disability ranging from mild to severe (PMID: 19012874; 29271092; 33853164; 33853164). Table 1 in PMID: 37605258, lists KIRREL3 variants and demonstrates that the variants maybe either de novo (9/16) or inherited from one of the parents (7/9). (PMID: 37605258). The KIRREL3 variants are either absent from control databases or are present at a very low frequency.; to: At least 12 missense KIRREL3 variants have been reported in 12 unrelated cases with a neurodevelopmental disorder, that includes intellectual disability ranging from mild to severe (PMID: 29271092; 33853164; 33853164). Table 1 in PMID: 37605258, reviews KIRREL3 variants and demonstrates that the variants maybe either de novo (4/11) or inherited from one of the parents (7/11)(mode of inheritance was unknown for one of the variants). The KIRREL3 variants are either absent from controls or are present at a very low frequency. However, the three variants reported in PMID: 19012874, were shown to be present in publicly databases at a high frequency (see KIRREL3 OMIM entry).
Intellectual disability v5.441 KIRREL3 Sarah Leigh Classified gene: KIRREL3 as Amber List (moderate evidence)
Intellectual disability v5.441 KIRREL3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.441 KIRREL3 Sarah Leigh Gene: kirrel3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.440 KIRREL3 Sarah Leigh reviewed gene: KIRREL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29271092; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.440 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 29271092; 37605258
Intellectual disability v5.439 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 29271092:37605258
Intellectual disability v5.438 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164; 37605258
Intellectual disability v5.437 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164; 33853164; 37605258
Intellectual disability v5.436 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164
Intellectual disability v5.435 KIRREL3 Sarah Leigh Mode of inheritance for gene: KIRREL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v3.10 LMNA Sarah Leigh Tag Q1_24_promote_green tag was added to gene: LMNA.
Tag Q1_24_NHS_review tag was added to gene: LMNA.
Pigmentary skin disorders v3.10 LMNA Sarah Leigh edited their review of gene: LMNA: Added comment: LMNA variants have been associated with various conditions, including Hutchinson-Gilford progeria (OMIM:176670) and Mandibuloacral dysplasia (OMIM:248370). Skin mottling has been reported in both of these conditions, and hyper and hypopigmentation is a feature of Mandibuloacral dysplasia (OMIM:248370). Numerous LMNA variants have been reported in these conditions.; Changed rating: GREEN
Pigmentary skin disorders v3.10 LMNA Sarah Leigh Classified gene: LMNA as Amber List (moderate evidence)
Pigmentary skin disorders v3.10 LMNA Sarah Leigh Gene: lmna has been classified as Amber List (Moderate Evidence).
Pigmentary skin disorders v3.9 LMNA Sarah Leigh Added comment: Comment on mode of inheritance: Hutchinson-Gilford progeria, OMIM:176670 is monoallelic, Mandibuloacral dysplasia, OMIM:248370 is biallelic
Pigmentary skin disorders v3.9 LMNA Sarah Leigh Mode of inheritance for gene: LMNA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pigmentary skin disorders v3.8 LMNA Sarah Leigh Phenotypes for gene: LMNA were changed from Hutchinson-Gilford progeria syndrome (HGPS) (MIM 176670); Mandibuloacral dysplasia with type A lipodystrophy (MADA) to Hutchinson-Gilford progeria, OMIM:176670; Hutchinson-Gilford progeria syndrome, MONDO:0008310; Mandibuloacral dysplasia, OMIM:248370; mandibuloacral dysplasia with type A lipodystrophy MONDO:0009557
Pigmentary skin disorders v3.7 LMNA Sarah Leigh Publications for gene: LMNA were set to PMID: 12714972; https://www.ncbi.nlm.nih.gov/books/NBK1121/#; 12075506; 17848409
Retinal disorders v4.56 UBAP1L Hannah Knight reviewed gene: UBAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38293907, PMID: 28041643; Phenotypes: Rod-cone dystrophy, cone-rod dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 LCP2 Hannah Knight reviewed gene: LCP2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37211057, PMID: 36474126; Phenotypes: ?Immunodeficiency 81; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.24 PHYH Sarah Leigh Phenotypes for gene: PHYH were changed from Refsum disease to Refsum disease, OMIM:266500
Palmoplantar keratodermas v3.23 PHYH Sarah Leigh reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Palmoplantar keratodermas v3.23 PHYH Sarah Leigh Tag Q1_24_demote_red tag was added to gene: PHYH.
Tag Q1_24_expert_review tag was added to gene: PHYH.
Palmoplantar keratodermas v3.23 SLC27A4 Sarah Leigh Tag Q1_24_expert_review tag was added to gene: SLC27A4.
Palmoplantar keratodermas v3.23 SLC27A4 Sarah Leigh Phenotypes for gene: SLC27A4 were changed from Ichthyosis prematurity syndrome to Ichthyosis prematurity syndrome, OMIM:608649
Palmoplantar keratodermas v3.22 SLC27A4 Sarah Leigh Tag Q1_24_demote_red tag was added to gene: SLC27A4.
Palmoplantar keratodermas v3.22 SLC27A4 Sarah Leigh reviewed gene: SLC27A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 POPDC3 Sarah Leigh Classified gene: POPDC3 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 POPDC3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.30 POPDC3 Sarah Leigh Gene: popdc3 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.29 POPDC3 Sarah Leigh Tag watchlist was removed from gene: POPDC3.
Tag Q1_24_promote_green tag was added to gene: POPDC3.
Tag Q1_24_NHS_review tag was added to gene: POPDC3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.29 POPDC3 Sarah Leigh reviewed gene: POPDC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.29 POPDC3 Sarah Leigh Phenotypes for gene: POPDC3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 26, OMIM:618848 to Muscular dystrophy, limb-girdle, autosomal recessive 26, OMIM:618848; muscular dystrophy, limb-girdle, autosomal recessive 26, MONDO:0030014
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.28 POPDC3 Sarah Leigh Publications for gene: POPDC3 were set to 31610034
Likely inborn error of metabolism v4.129 TUSC3 Arina Puzriakova Publications for gene: TUSC3 were set to 27604308
Undiagnosed metabolic disorders v1.613 TUSC3 Arina Puzriakova Publications for gene: TUSC3 were set to 27604308
Congenital disorders of glycosylation v4.18 TUSC3 Arina Puzriakova Publications for gene: TUSC3 were set to 18455129; 18452889; 26864433; 27148795
Intellectual disability v5.434 TUSC3 Arina Puzriakova Publications for gene: TUSC3 were set to
Likely inborn error of metabolism v4.128 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from TUSC3-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 7 to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Fetal anomalies v3.133 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7 to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Undiagnosed metabolic disorders v1.612 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from TUSC3-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 7 to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Congenital disorders of glycosylation v4.17 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from Mental retardation, autosomal recessive 7 611093; TUSC3-CDG (Disorders of protein N-glycosylation) to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Intellectual disability v5.433 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from Mental retardation, autosomal recessive 7, 611093; MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7 (MRT7) to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Intellectual disability v5.432 CC2D1A Arina Puzriakova Publications for gene: CC2D1A were set to
Retinal disorders v4.56 LRRC32 Hannah Knight gene: LRRC32 was added
gene: LRRC32 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to PMID: 30976112; PMID: 35656379
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay
Review for gene: LRRC32 was set to AMBER
Added comment: PMID: 30976112 - homozygous founder variant (p.R544X) identified in two consanguineous families of Palestinian descent - sister and brother, and an unrelated boy. All with cleft palate, proliferative retinopathy, and developmental delay. Segregated with disease in both families.
PMID: 35656379 - rare homozygous missense in a patient who presented with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy
Sources: Literature
Intellectual disability v5.431 CC2D1A Arina Puzriakova Phenotypes for gene: CC2D1A were changed from Mental retardation, autosomal recessive 3, 608443; MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 3 (MRT3) to Intellectual developmental disorder, autosomal recessive 3, OMIM:608443
Fetal anomalies v3.132 CC2D1A Arina Puzriakova Phenotypes for gene: CC2D1A were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 3 to Intellectual developmental disorder, autosomal recessive 3, OMIM:608443
White matter disorders and cerebral calcification - narrow panel v3.31 RARS Arina Puzriakova Publications for gene: RARS were set to 24777941; 27564080
Intellectual disability v5.430 RARS Arina Puzriakova Publications for gene: RARS were set to 31814314; 28905880; 24777941; 30500859
Intellectual disability v5.429 LRRC32 Hannah Knight reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35656379; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited white matter disorders v1.179 RARS Arina Puzriakova Publications for gene: RARS were set to 24777941; 27564080
Early onset or syndromic epilepsy v4.163 RARS Arina Puzriakova Phenotypes for gene: RARS were changed from Leukodystrophy, hypomyelinating, 9 616140 to Leukodystrophy, hypomyelinating, 9, OMIM:616140
Inherited white matter disorders v1.178 RARS Arina Puzriakova Phenotypes for gene: RARS were changed from Leukodystrophy, hypomyelinating, 9 616140 to Leukodystrophy, hypomyelinating, 9, OMIM:616140
White matter disorders and cerebral calcification - narrow panel v3.30 RARS Arina Puzriakova Phenotypes for gene: RARS were changed from Leukodystrophy, hypomyelinating, 9 616140 to Leukodystrophy, hypomyelinating, 9, OMIM:616140
Intellectual disability v5.429 RARS Arina Puzriakova Phenotypes for gene: RARS were changed from Cerebral hypomyelination; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Nystagmus; Ataxia; Feeding difficulties to Leukodystrophy, hypomyelinating, 9, OMIM:616140
Intellectual disability v5.428 ASPM Arina Puzriakova Publications for gene: ASPM were set to
Severe microcephaly v4.59 ASPM Arina Puzriakova Publications for gene: ASPM were set to
Malformations of cortical development v4.23 ASPM Arina Puzriakova Publications for gene: ASPM were set to 12355089
Fetal anomalies v3.131 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from PRIMARY AUTOSOMAL RECESSIVE MICROCEPHALY to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Intellectual disability v5.427 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive, 608716; PRIMARY AUTOSOMAL RECESSIVE MICROCEPHALY to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Severe microcephaly v4.58 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive; MCPH; primary microcephaly; Primary Microcephaly, Recessive; Autosomal recessive primary microcephaly (MCPH) ; Microcephaly 5, primary, autosomal recessive, 608716; Microcephaly 5, Primary, Autosomal Recessive to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Malformations of cortical development v4.22 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive 608716 to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Intellectual disability v5.426 RARS Arina Puzriakova Publications for gene: RARS were set to 31814314; 28905880; 24777941
Malformations of cortical development v4.21 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to
Early onset or syndromic epilepsy v4.162 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to 21834044; 20890278; 20729831; 28377545
Severe microcephaly v4.57 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to
Intellectual disability v5.425 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to
Intellectual disability v5.424 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from Microcephaly, Cortical Malformations, and Mental Retardation; Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317; MICROCEPHALY CORTICAL MALFORMATIONS AND MENTAL RETARDATION (MCMMR) to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Early onset or syndromic epilepsy v4.161 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317 to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Severe microcephaly v4.56 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from MCPH; primary microcephaly; Primary Microcephaly 2 With or Without Cortical Malformations; Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317; microcephaly cortical malformations and mental retardation (MCMMR), 604317; Microcephaly 2, Primary, Autosomal Recessive, With Or Without Cortical Malformations to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Malformations of cortical development v4.20 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 604317 to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Intellectual disability v5.423 MCPH1 Arina Puzriakova Publications for gene: MCPH1 were set to
Severe microcephaly v4.55 MCPH1 Arina Puzriakova Publications for gene: MCPH1 were set to
Intellectual disability v5.422 MCPH1 Arina Puzriakova Phenotypes for gene: MCPH1 were changed from genetic heterogeneity Microcephaly 1, primary, autosomal recessive, 251200; MICROCEPHALY PRIMARY TYPE 1 (MCPH1) to Microcephaly 1, primary, autosomal recessive, OMIM:251200
Severe microcephaly v4.54 MCPH1 Arina Puzriakova Phenotypes for gene: MCPH1 were changed from MCPH; primary microcephaly; Primary Microcephaly, Recessive; Microcephaly 1, primary, autosomal recessive, 251200; Microcephaly 1, Primary, Autosomal Recessive to Microcephaly 1, primary, autosomal recessive, OMIM:251200
Early onset or syndromic epilepsy v4.160 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Early onset or syndromic epilepsy v4.159 HSD17B10 Arina Puzriakova Classified gene: HSD17B10 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.159 HSD17B10 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - seizures can be a reported feature of HSD10 disease (PMID: 12872843; 22132097; 26950678; 27295195; 34765396)
Early onset or syndromic epilepsy v4.159 HSD17B10 Arina Puzriakova Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.19 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Classified gene: HSD17B10 as Amber List (moderate evidence)
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - optic nerve atrophy with visual loss can be a reported feature of HSD10 disease (PMIDs: 22132097; 26950678; 27295195)
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.71 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova changed review comment from: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 31654490); to: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 27295195; 31654490)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Classified gene: HSD17B10 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 31654490)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.69 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to
Childhood onset dystonia, chorea or related movement disorder v3.68 HSD17B10 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: HSD17B10.
Childhood onset dystonia, chorea or related movement disorder v3.68 HSD17B10 Arina Puzriakova reviewed gene: HSD17B10: Rating: GREEN; Mode of pathogenicity: None; Publications: 19706438, 22132097, 12696021, 26950678, 27604308, 12872843, 12555940; Phenotypes: HSD10 mitochondrial disease, OMIM:300438; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Optic neuropathy v4.17 HSD17B10 Arina Puzriakova gene: HSD17B10 was added
gene: HSD17B10 was added to Optic neuropathy. Sources: Literature
Q1_24_promote_green tags were added to gene: HSD17B10.
Mode of inheritance for gene: HSD17B10 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: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Phenotypes for gene: HSD17B10 were set to HSD10 mitochondrial disease, OMIM:300438
Review for gene: HSD17B10 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for intellectual development disorder syndromic X-linked type 10. Multiple unrelated individuals (at least 8 variants) with supportive functional studies reported in the literature, including some affected female carriers presenting with mild to moderate developmental delay or intellectual disability.
Phenotype in severely affected males comprises developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation.
Sources: Literature
Early onset or syndromic epilepsy v4.158 HSD17B10 Arina Puzriakova gene: HSD17B10 was added
gene: HSD17B10 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_24_promote_green tags were added to gene: HSD17B10.
Mode of inheritance for gene: HSD17B10 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: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Phenotypes for gene: HSD17B10 were set to HSD10 mitochondrial disease, OMIM:300438
Review for gene: HSD17B10 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for intellectual development disorder syndromic X-linked type 10. Multiple unrelated individuals (at least 8 variants) with supportive functional studies reported in the literature, including some affected female carriers presenting with mild to moderate developmental delay or intellectual disability.
Phenotype in severely affected males comprises developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation.
Sources: Literature
Likely inborn error of metabolism v4.127 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308
Intellectual disability v5.421 HSD17B10 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'XL, biallelic in females' to 'XL, monoallelic in females' as female patients harbouring heterozygous variants have been described. Some carrier females shown to have mild to moderate developmental delay or intellectual disability (PMIDs: 12112118; 16148061; 22127393; 34765396)
Intellectual disability v5.421 HSD17B10 Arina Puzriakova Mode of inheritance for gene: HSD17B10 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.420 HSD17B10 Arina Puzriakova Tag Q1_24_MOI tag was added to gene: HSD17B10.
Childhood onset dystonia, chorea or related movement disorder v3.68 HSD17B10 Arina Puzriakova Mode of inheritance for gene: HSD17B10 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.420 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to
Possible mitochondrial disorder - nuclear genes v3.87 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to
Mitochondrial disorders v4.157 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from HSD10 mitochondrial disease 300438 to HSD10 mitochondrial disease, OMIM:300438
Intellectual disability v5.419 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from 17-beta-hydroxysteroid dehydrogenase X deficiency, 300438Mental retardation, X-linked syndromic 10, 300220Mental retardation, X-linked 17/31, microduplication, 300705; 2-METHYL-3-HYDROXYBUTYRYL-COA DEHYDROGENASE DEFICIENCY (MHBD DEFICIENCY) to HSD10 mitochondrial disease, OMIM:300438
Childhood onset dystonia, chorea or related movement disorder v3.67 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from to HSD10 mitochondrial disease, OMIM:300438
Likely inborn error of metabolism v4.126 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from HSD10 mitochondrial disease 300438 to HSD10 mitochondrial disease, OMIM:300438
Possible mitochondrial disorder - nuclear genes v3.86 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from HSD10 mitochondrial disease, 300438 to HSD10 mitochondrial disease, OMIM:300438
Undiagnosed metabolic disorders v1.611 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from HSD10 mitochondrial disease 300438 to HSD10 mitochondrial disease, OMIM:300438
Early onset or syndromic epilepsy v4.157 COL4A3BP Arina Puzriakova Classified gene: COL4A3BP as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.157 COL4A3BP Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Early onset or syndromic epilepsy v4.157 COL4A3BP Arina Puzriakova Gene: col4a3bp has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.156 COL4A3BP Arina Puzriakova commented on gene: COL4A3BP: Added new-gene-name tag, new approved HGNC gene symbol for COL4A3BP is CERT1
Early onset or syndromic epilepsy v4.156 COL4A3BP Arina Puzriakova Tag new-gene-name tag was added to gene: COL4A3BP.
Early onset or syndromic epilepsy v4.156 COL4A3BP Arina Puzriakova gene: COL4A3BP was added
gene: COL4A3BP was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_24_promote_green tags were added to gene: COL4A3BP.
Mode of inheritance for gene: COL4A3BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Phenotypes for gene: COL4A3BP were set to Intellectual developmental disorder, autosomal dominant 34, OMIM:616351
Review for gene: COL4A3BP was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM and in Gene2Phenotype (definitive disease confidence category for CERT1-related INTELLECTUAL DISABILITY)

At least 35 cases have been reported in literature with heterozygous variants. Seizures were observed in at least 19 individuals.
Sources: Literature
Intellectual disability v5.418 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465
Intellectual disability v5.416 COL4A3BP Arina Puzriakova Phenotypes for gene: COL4A3BP were changed from INTELLECTUAL DISABILITY to Intellectual developmental disorder, autosomal dominant 34, OMIM:616351
Intellectual disability v5.415 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962
Paediatric or syndromic cardiomyopathy v3.43 PLD1 Jesse Hayesmoore changed review comment from: On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines. ; to: On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines.
Paediatric or syndromic cardiomyopathy v3.43 PLD1 Jesse Hayesmoore changed review comment from: On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign). Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.; to: On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD.

I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel.

Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines.
Paediatric or syndromic cardiomyopathy v3.43 PLD1 Jesse Hayesmoore reviewed gene: PLD1: Rating: RED; Mode of pathogenicity: Other; Publications: PMIDs: 27799408 and 33645542; Phenotypes: Paediatric cardiomyopathy, cardiac valvular defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary neuropathy or pain disorder v3.82 GAN Tracy Lester reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301315; Phenotypes: neuropathy, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.414 GAN Tracy Lester reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301315; Phenotypes: Intellectual disability, developmental delay, neuropathy, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 AMFR Boaz Palterer gene: AMFR was added
gene: AMFR was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: AMFR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AMFR were set to 38277122
Phenotypes for gene: AMFR were set to Severe VZV; Varicella; HLH; Hemophagocytic lymphohistyocytosis
Penetrance for gene: AMFR were set to Incomplete
Review for gene: AMFR was set to RED
Added comment: 1 patient from one kindred with severe disseminated VZV and HLH, incomplete penetrance as mother and siblings are not affected. Extensive functional ex-vivo and in-vitro data.
Sources: Literature
Likely inborn error of metabolism v4.125 GSTZ1 Achchuthan Shanmugasundram Classified gene: GSTZ1 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.125 GSTZ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:27876694 and reviewed by Saikat Santra, there are three boys and three girls with maleylacetoacetate isomerase deficiency (MAAID), identified by newborn screening with mildly elevated succinylacetone (SA) by mass spectrometry on dried blood spot.

Four of them were identified with homozygous GSTZ1 variants, one with compound heterozygous variants and one with heterozygous variant.

Hence, there is sufficient evidence available for the association of biallelic GSTZ1 variants with MAAID and this gene can be promoted to green rating in the next GMS review.
Likely inborn error of metabolism v4.125 GSTZ1 Achchuthan Shanmugasundram Gene: gstz1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.124 GSTZ1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with maleylacetoacetate isomerase deficiency in OMIM (MIM #617596), but not with any phenotypes in Gene2Phenotype.
Likely inborn error of metabolism v4.124 GSTZ1 Achchuthan Shanmugasundram Phenotypes for gene: GSTZ1 were changed from Biochemical to [Maleylacetoacetate isomerase deficiency], OMIM:617596
Likely inborn error of metabolism v4.123 GSTZ1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: GSTZ1.
Tag Q1_24_NHS_review tag was added to gene: GSTZ1.
Likely inborn error of metabolism v4.123 GSTZ1 Achchuthan Shanmugasundram reviewed gene: GSTZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: [Maleylacetoacetate isomerase deficiency], OMIM:617596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.155 KCNA3 Achchuthan Shanmugasundram Classified gene: KCNA3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.155 KCNA3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:37964487 and reviewed by Gavin Ryan, epilepsy was present in eight of twelve patients for whom detailed clinical information was available. Hence, this gene can be promoted to green rating in this panel in the next GMS review.
Early onset or syndromic epilepsy v4.155 KCNA3 Achchuthan Shanmugasundram Gene: kcna3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.154 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Intellectual disability; Developmental Delay; Epilepsy to Neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v4.153 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to PMID: 37964487
Early onset or syndromic epilepsy v4.152 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA3.
Tag Q1_24_NHS_review tag was added to gene: KCNA3.
Early onset or syndromic epilepsy v4.152 KCNA3 Achchuthan Shanmugasundram reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Classified gene: KCNA3 as Amber List (moderate evidence)
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:37964487 and reviewed by Gavin Ryan, 12 patients had developmental delays, of which nine patients had mild, moderate or severe intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Gene: kcna3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Intellectual disability; Developmental Delay; Epilepsy to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to 37964487
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to PMID: 37964487
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.82 HMBS Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available (three unrelated families) for the association of biallelic HMBS variants with peripheral neuropathy. Hence, the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Hereditary neuropathy or pain disorder v3.82 HMBS Achchuthan Shanmugasundram Mode of inheritance for gene: HMBS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.81 HMBS Achchuthan Shanmugasundram Phenotypes for gene: HMBS were changed from AIP, Abdominal pain, psychosis, depression, seizures, axonal predominantly motor neuropathy; Porphyria, acute intermittent, 176000 to Porphyria, acute intermittent, OMIM:76000; Porphyria, acute intermittent, nonerythroid variant, OMIM:176000; Leukoencephalopathy, HP:0002352; hereditary peripheral neuropathy, MONDO:0020127
Hereditary neuropathy or pain disorder v3.80 HMBS Achchuthan Shanmugasundram edited their review of gene: HMBS: Changed phenotypes to: Porphyria, acute intermittent, OMIM:76000, Porphyria, acute intermittent, nonerythroid variant, OMIM:176000, Leukoencephalopathy, HP:0002352, hereditary peripheral neuropathy, MONDO:0020127
Hereditary neuropathy or pain disorder v3.80 HMBS Achchuthan Shanmugasundram Publications for gene: HMBS were set to
Hereditary neuropathy or pain disorder v3.79 HMBS Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: HMBS.
Hereditary neuropathy or pain disorder v3.79 HMBS Achchuthan Shanmugasundram reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27558376, 34089223; Phenotypes: Leukoencephalopathy, HP:0002352, hereditary peripheral neuropathy, MONDO:0020127; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Classified gene: HMBS as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Gene: hmbs has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.53 HMBS Achchuthan Shanmugasundram Phenotypes for gene: HMBS were changed from Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064 to Leukoencephalopathy, HP:0002352; cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HMBS.
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram edited their review of gene: HMBS: Changed phenotypes to: Leukoencephalopathy, HP:0002352, cerebellar ataxia, MONDO:0000437
Childhood onset hereditary spastic paraplegia v4.39 HMBS Achchuthan Shanmugasundram Classified gene: HMBS as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v4.39 HMBS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with spastic paraparesis. Hence, this gene can be promoted to green rating in the next GMS review.
Childhood onset hereditary spastic paraplegia v4.39 HMBS Achchuthan Shanmugasundram Gene: hmbs has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v4.38 HMBS Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HMBS.
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram gene: HMBS was added
gene: HMBS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 27558376; 34089223
Phenotypes for gene: HMBS were set to Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064
Review for gene: HMBS was set to GREEN
Added comment: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.38 HMBS Achchuthan Shanmugasundram gene: HMBS was added
gene: HMBS was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 27558376; 34089223
Phenotypes for gene: HMBS were set to Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064
Review for gene: HMBS was set to GREEN
Added comment: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.29 HMBS Achchuthan Shanmugasundram Classified gene: HMBS as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v3.29 HMBS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with white matter abnormalities. Hence, this gene can be promoted to green rating in the next GMS review.
White matter disorders and cerebral calcification - narrow panel v3.29 HMBS Achchuthan Shanmugasundram Gene: hmbs has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v3.28 HMBS Achchuthan Shanmugasundram Phenotypes for gene: HMBS were changed from to Leukoencephalopathy, HP:0002352
White matter disorders and cerebral calcification - narrow panel v3.27 HMBS Achchuthan Shanmugasundram Publications for gene: HMBS were set to 27558376, 27271711
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HMBS.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene has been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene has been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported three patients from two unrelated families with; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27558376, 34089223; Phenotypes: Leukoencephalopathy, HP:0002352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.22 LGI3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram changed review comment from: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature; to: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Arthrogryposis v5.22 LGI3 Achchuthan Shanmugasundram changed review comment from: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability.

Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature; to: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability.

Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Arthrogryposis v5.22 LGI3 Achchuthan Shanmugasundram Classified gene: LGI3 as Amber List (moderate evidence)
Arthrogryposis v5.22 LGI3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Arthrogryposis v5.22 LGI3 Achchuthan Shanmugasundram Gene: lgi3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.21 LGI3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LGI3.
Arthrogryposis v5.21 LGI3 Achchuthan Shanmugasundram gene: LGI3 was added
gene: LGI3 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to 35948005
Phenotypes for gene: LGI3 were set to Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007
Review for gene: LGI3 was set to GREEN
Added comment: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability.

Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Classified gene: LGI3 as Amber List (moderate evidence)
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated families and mouse model) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Gene: lgi3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LGI3.
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram gene: LGI3 was added
gene: LGI3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to 35948005
Phenotypes for gene: LGI3 were set to Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007
Review for gene: LGI3 was set to GREEN
Added comment: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v4.50 TP53 Sarah Leigh Classified gene: TP53 as Red List (low evidence)
Skeletal dysplasia v4.50 TP53 Sarah Leigh Gene: tp53 has been classified as Red List (Low Evidence).
Skeletal dysplasia v4.49 TP53 Sarah Leigh edited their review of gene: TP53: Added comment: This gene is rated as red, because the variants are somatic, occurring in the tumour.; Changed rating: RED
Skeletal dysplasia v4.49 TP53 Sarah Leigh changed review comment from: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
This gene is rated as red, because the variants are somatic, occurring in the tumour.; to: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
Skeletal dysplasia v4.49 TP53 Sarah Leigh changed review comment from: PMID: 33147331 reports inactivating TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in
tumorigenesis, giving rise to the dedifferentiated component in DDCS.; to: PMID: 33147331 reports inactivating somatic TP53 variants in dedifferentiated components of dedifferentiated chondrosarcoma. Due to the distribution of TP53 variants in the tumours, the authors of PMID: 33147331, conclude that these variants occur late in tumorigenesis, giving rise to the dedifferentiated component in DDCS.
This gene is rated as red, because the variants are somatic, occurring in the tumour.
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Deleted their comment
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Classified gene: IDH2 as Red List (low evidence)
Skeletal dysplasia v4.49 IDH2 Sarah Leigh Gene: idh2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v4.48 IDH2 Sarah Leigh changed review comment from: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as amber, because the variants are somatic, occurring in the tumour.; to: IDH2 variants have been associated with D-2-hydroxyglutaric aciduria 2 (OMIM:613657). PMID: 36042521 reports IDH2 variants at codon 172 (p.R172T, p.R172S, p.R172G) in seven cases of chondrosarcoma central conventional and two case of chondrosarcoma central dedifferentiated. The authors of PMID: 36042521 comment "IDH2 tumours present as larger tumours and on average over a decade later than IDH1 tumours". Based on the finding that the IDH1 and IDH2 tumours have similar molecular ages, the authors suggest that the IDH2 tumours have slower rate of cell division, with the result that the tumours undergo growth arrest and become calcified. They go onto speculate, that if this is the case, many IDH2 tumours would not become malignant and would only be detected if medical imaging was being used for an unrelated cause.
This gene is rated as red, because the variants are somatic, occurring in the tumour.
Early onset or syndromic epilepsy v4.152 KCNA3 Gavin Ryan gene: KCNA3 was added
gene: KCNA3 was added to Early onset or syndromic epilepsy. Sources: Expert Review
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNA3 were set to PMID: 37964487
Phenotypes for gene: KCNA3 were set to Intellectual disability; Developmental Delay; Epilepsy
Penetrance for gene: KCNA3 were set to unknown
Review for gene: KCNA3 was set to GREEN
Added comment: Soldovieri et al identified 14 de novo missense variants in KCNA3 gene. The majority of individuals presented with ID, developmental delay, and epilepsy, amongst other features. Functional studies showed loss-of-function effects for some variants and possible gain-of-function for others. One of these variants has also been identified in NHS GMS WGS patient with consistent features.
Sources: Expert Review
Intellectual disability v5.409 KCNA3 Gavin Ryan gene: KCNA3 was added
gene: KCNA3 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNA3 were set to PMID: 37964487
Phenotypes for gene: KCNA3 were set to Intellectual disability; Developmental Delay; Epilepsy
Penetrance for gene: KCNA3 were set to unknown
Review for gene: KCNA3 was set to GREEN
Added comment: Soldovieri et al identified 14 de novo missense variants in KCNA3 gene. The majority of individuals presented with ID, developmental delay, and epilepsy, amongst other features. Functional studies showed loss-of-function effects for some variants and possible gain-of-function for others. One of these variants has also been identified in NHS GMS WGS patient with consistent features.
Sources: Expert Review
Intellectual disability v5.409 BAZ2B Dmitrijs Rots gene: BAZ2B was added
gene: BAZ2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to PMID: 31999386
Phenotypes for gene: BAZ2B were set to developmental delay, intellectual disability and autism spectrum disorder
Review for gene: BAZ2B was set to GREEN
Added comment: BAZ2B gene is intolerant to LoF variants in population (pLI=1) and PMID: 31999386 described that de novo LoF variants are statistically enriched among NDD cases & summarize 10 cases. Enough evidence for the green rating.
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.21 FCGR3B Dmitrijs Rots reviewed gene: FCGR3B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v4.53 ZNF335 Dmitrijs Rots reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.409 ABCC9 Tracy Lester reviewed gene: ABCC9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ectodermal dysplasia v3.28 LEF1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are four unrelated families reported with monoallelic variants and a single individual reported with biallelic variants. Hence, this gene should be promoted to green rating in the next GMS review and the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.; to: Comment on list classification: There are four unrelated families reported with monoallelic variants and a single individual reported with biallelic variants. Hence, this gene should be promoted to green rating in the next GMS review and the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Ectodermal dysplasia v3.28 LEF1 Achchuthan Shanmugasundram Classified gene: LEF1 as Amber List (moderate evidence)
Ectodermal dysplasia v3.28 LEF1 Achchuthan Shanmugasundram Gene: lef1 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.27 LEF1 Achchuthan Shanmugasundram Classified gene: LEF1 as Red List (low evidence)
Ectodermal dysplasia v3.27 LEF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated families reported with monoallelic variants and a single individual reported with biallelic variants. Hence, this gene should be promoted to green rating in the next GMS review and the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Ectodermal dysplasia v3.27 LEF1 Achchuthan Shanmugasundram Gene: lef1 has been classified as Red List (Low Evidence).
Ectodermal dysplasia v3.26 LEF1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: Germline variants in this gene have not yet been associated with any phenotypes in OMIM, but monoallelic variants have been associated with LEF1-related ectodermal dysplasia and limb malformation in Gene2Phenotype ('moderate' rating on the DD panel).
Ectodermal dysplasia v3.26 LEF1 Achchuthan Shanmugasundram Phenotypes for gene: LEF1 were changed from ectodermal dysplasia syndrome, MONDO:0019287 to ectodermal dysplasia syndrome, MONDO:0019287
Ectodermal dysplasia v3.25 LEF1 Achchuthan Shanmugasundram Phenotypes for gene: LEF1 were changed from Ectodermal dysplasia, no OMIM# yet to ectodermal dysplasia syndrome, MONDO:0019287
Ectodermal dysplasia v3.24 LEF1 Achchuthan Shanmugasundram Publications for gene: LEF1 were set to 32022899
Ectodermal dysplasia v3.23 LEF1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LEF1.
Ectodermal dysplasia v3.23 LEF1 Achchuthan Shanmugasundram reviewed gene: LEF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35583550; Phenotypes: ectodermal dysplasia syndrome, MONDO:0019287, limb malformations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Iron metabolism disorders - NOT common HFE mutations v2.4 STAB1 Achchuthan Shanmugasundram Classified gene: STAB1 as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v2.4 STAB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of STAB1 gene to green rating in the next GMS review.
Iron metabolism disorders - NOT common HFE mutations v2.4 STAB1 Achchuthan Shanmugasundram Gene: stab1 has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v2.3 STAB1 Achchuthan Shanmugasundram changed review comment from: PMID:37490907 reported the identification of biallelic variants in STAB10 gene in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies.; to: PMID:37490907 reported the identification of biallelic variants in STAB10 gene in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Iron metabolism disorders - NOT common HFE mutations v2.3 STAB1 Achchuthan Shanmugasundram commented on gene: STAB1: PMID:37490907 reported the identification of biallelic variants in STAB10 gene in 10 individuals from 7 families with unexplained hyperferritinaemia without iron overload. All of them were in good health and had no dysmorphologies, psycho-motor development abnormalities, hearing or vision disorders, or other pathologies.
Iron metabolism disorders - NOT common HFE mutations v2.3 STAB1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: STAB1.
Iron metabolism disorders - NOT common HFE mutations v2.3 STAB1 Achchuthan Shanmugasundram reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37490907; Phenotypes: Genetic hyperferritinemia without iron overload (disorder), SNOMED:766929007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Classified gene: NOS1AP as Amber List (moderate evidence)
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark and reported in PMID:33523862, there are two unrelated individuals with homozygous NOS1AP variants (c.428G>A/ p.Cys143Tyr & c.345-3T-G) and presenting with nephrotic syndrome, type 22 (MIM# 619155).

Introduction of patient variant (c.428G>A) has resulted in aberrant glomeruli formation in kidney organoids. In addition, homozygous exon 3-deleted mice recapitulated the human phenotype, exhibiting proteinuria, foot process effacement, and glomerulosclerosis.

Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Gene: nos1ap has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.5 NOS1AP Achchuthan Shanmugasundram Phenotypes for gene: NOS1AP were changed from Nephrotic syndrome, type 22, MIM# 619155 to Nephrotic syndrome, type 22, OMIM:619155
Proteinuric renal disease v4.4 NOS1AP Achchuthan Shanmugasundram Publications for gene: NOS1AP were set to
Proteinuric renal disease v4.3 NOS1AP Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: NOS1AP.
Proteinuric renal disease v4.3 NOS1AP Achchuthan Shanmugasundram reviewed gene: NOS1AP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33523862; Phenotypes: Nephrotic syndrome, type 22, OMIM:619155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram edited their review of gene: MTSS1L: Changed phenotypes to: Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram changed review comment from: Added new-gene-name tag, new approved HGNC gene symbol for MTSS1L is MTSS2.; to: New approved HGNC gene symbol for MTSS1L is MTSS2.
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram commented on gene: MTSS1L
Cytopenias and congenital anaemias v1.116 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Hypereosinophilic syndrome, idiopathic, resistant to imatinib 607685 to Hypereosinophilic syndrome, idiopathic, resistant to imatinib, OMIM:607685
Inherited predisposition to GIST v1.14 PDGFRA Arina Puzriakova Publications for gene: PDGFRA were set to
Adult solid tumours cancer susceptibility v2.29 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Gastrointestinal stromal tumor to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, OMIM:175510; Familial Gastrointestinal stromal tumour; Familial GIST
Childhood solid tumours cancer susceptibility v1.26 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Familial GIST; Gastrointestinal stromal tumor, somatic 606764 to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, OMIM:175510; Familial Gastrointestinal stromal tumour; Familial GIST
Sarcoma cancer susceptibility v1.24 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Familial GIST; Gastrointestinal stromal tumor, somatic 606764 to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, OMIM:175510; Familial Gastrointestinal stromal tumour; Familial GIST
Childhood solid tumours v4.15 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Familial Gastrointestinal stromal tumour; Gastrointestinal stromal tumor, somatic 606764; Familial GIST; Gastrointestinal stromal tumor, somatic, 606764 to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, OMIM:175510; Familial Gastrointestinal stromal tumour; Familial GIST
Adult solid tumours for rare disease v1.40 PDGFRA Arina Puzriakova Phenotypes for gene: PDGFRA were changed from Gastrointestinal stromal tumor to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, OMIM:175510
Hereditary Erythrocytosis v2.6 PKLR Arina Puzriakova Publications for gene: PKLR were set to 22274579
Hereditary Erythrocytosis v2.5 PKLR Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'both mono- and biallelic' to 'monoallelic' only. Limited evidence but historic reports linked heterozygous variants in the PKLR gene to elevation of red cell ATP levels, accompanied by elevated red cell pyruvate kinase activity and mild erythrocytosis. Patients were asymptomatic and no recent cases have been published therefore Red rating is appropriate (PMIDs: 9090535; 4160306; 14300761; 7426754).

Biallelic variants cause pyruvate kinase deficiency which results in nonspherocytic hemolytic anemia rather than erythrocytosis.
Hereditary Erythrocytosis v2.5 PKLR Arina Puzriakova Mode of inheritance for gene: PKLR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal hydrops v1.63 PKLR Arina Puzriakova Classified gene: PKLR as Green List (high evidence)
Fetal hydrops v1.63 PKLR Arina Puzriakova Added comment: Comment on list classification: Rating Green as non-immune hydrops fetalis reported in multiple cases of Pyruvate kinase deficiency.

Green rating also inline with classification on equivalent GMS panel R21 Fetal anomalies (v3.0).
Fetal hydrops v1.63 PKLR Arina Puzriakova Gene: pklr has been classified as Green List (High Evidence).
Fetal hydrops v1.62 PKLR Arina Puzriakova Phenotypes for gene: PKLR were changed from Pyruvate Kinase deficiency to Pyruvate kinase deficiency, OMIM:266200
Cytopenias and congenital anaemias v1.115 PKLR Arina Puzriakova Phenotypes for gene: PKLR were changed from PYRUVATE KINASE DEFICIENCY; Enzyme Disorder; Pyruvate kinase deficiency, 266200 to Pyruvate kinase deficiency, OMIM:266200
Rare anaemia v3.7 PKLR Arina Puzriakova Phenotypes for gene: PKLR were changed from Enzyme Disorder; PYRUVATE KINASE DEFICIENCY; Pyruvate kinase deficiency; 266200 PYRUVATE KINASE DEFICIENCY; 266200 Pyruvate kinase deficiency; Pyruvate kinase deficiency, 266200 to Pyruvate kinase deficiency, OMIM:266200
Fetal anomalies v3.130 PKLR Arina Puzriakova Phenotypes for gene: PKLR were changed from Pyruvate kinase deficiency 266200 to Pyruvate kinase deficiency, OMIM:266200
Hereditary Erythrocytosis v2.4 PKLR Arina Puzriakova Phenotypes for gene: PKLR were changed from Familial erythrocytosis to Adenosine triphosphate, elevated, of erythrocytes, OMIM:102900
Ichthyosis and erythrokeratoderma v3.22 POMP Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: POMP.
Tag Q1_24_expert_review tag was added to gene: POMP.
Palmoplantar keratodermas v3.22 POMP Arina Puzriakova Tag Q1_24_demote_red tag was added to gene: POMP.
Tag Q1_24_expert_review tag was added to gene: POMP.
Ichthyosis and erythrokeratoderma v3.22 POMP Arina Puzriakova Classified gene: POMP as Red List (low evidence)
Ichthyosis and erythrokeratoderma v3.22 POMP Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to support the gene-disease association but based on previous reviews, POMP is currently classified as Red on this panel due the single 1bp deletion identified in all cases to date residing in the 5'UTR of the POMP gene.

The gene rating is conflicting on the R166 Palmoplantar keratodermas, where POMP is rated Green for the same phenotype. This has been tagged for NHSE expert review, and therefore also tagging the association on this panel so that the two panels can be considered together and the overall classification be aligned.
Ichthyosis and erythrokeratoderma v3.22 POMP Arina Puzriakova Gene: pomp has been classified as Red List (Low Evidence).
Palmoplantar keratodermas v3.22 POMP Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

There is sufficient evidence to support a gene-disease association, however the pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).

If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).

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Supporting evidence (reviews copied from R165 panel):

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.; to: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

PPK is a key feature of KLICK syndrome, and there are sufficient cases to support causation (PMID:20226437 and PMID:27503413). However, the pathogenic variant reported in all cases so far is the same 1bp deletion in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).

If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).

---
Supporting evidence (reviews copied from R165 panel):

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.
Ichthyosis and erythrokeratoderma v3.21 POMP Arina Puzriakova Publications for gene: POMP were set to 27503413; 20226437
Palmoplantar keratodermas v3.22 POMP Arina Puzriakova Publications for gene: POMP were set to 27503413; 20226437
Ichthyosis and erythrokeratoderma v3.20 POMP Arina Puzriakova Phenotypes for gene: POMP were changed from Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952
Palmoplantar keratoderma and erythrokeratodermas v1.31 POMP Arina Puzriakova Phenotypes for gene: POMP were changed from Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952
Palmoplantar keratodermas v3.21 POMP Arina Puzriakova Phenotypes for gene: POMP were changed from Keratosis linearis with ichthyosis congenita and sclerosing keratoderma to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952
Palmoplantar keratodermas v3.20 POMP Arina Puzriakova Publications for gene: POMP were set to
Palmoplantar keratodermas v3.19 POMP Arina Puzriakova Classified gene: POMP as Green List (high evidence)
Palmoplantar keratodermas v3.19 POMP Arina Puzriakova Added comment: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

There is sufficient evidence to support a gene-disease association, however the pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).

If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).

---
Supporting evidence (reviews copied from R165 panel):

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.
Palmoplantar keratodermas v3.19 POMP Arina Puzriakova Gene: pomp has been classified as Green List (High Evidence).
Palmoplantar keratodermas v3.18 POMP Arina Puzriakova Classified gene: POMP as Green List (high evidence)
Palmoplantar keratodermas v3.18 POMP Arina Puzriakova Added comment: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

There is sufficient evidence to support a gene-disease association, however the pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).

If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).

---
Supporting evidence (reviews copied from R165 panel):

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.
Palmoplantar keratodermas v3.18 POMP Arina Puzriakova Gene: pomp has been classified as Green List (High Evidence).
Ichthyosis and erythrokeratoderma v3.19 POMP Arina Puzriakova Tag non-coding-known-pathogenic tag was added to gene: POMP.
Palmoplantar keratodermas v3.17 POMP Arina Puzriakova Tag promoter tag was added to gene: POMP.
Tag non-coding-known-pathogenic tag was added to gene: POMP.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.163 POMP Arina Puzriakova Phenotypes for gene: POMP were changed from CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Proteasome-associated autoinflammatory syndrome 2, 618048; combined immunodeficiency with autoinflammation to Proteasome-associated autoinflammatory syndrome 2, OMIM:618048; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Combined immunodeficiency with autoinflammation
Hereditary neuropathy or pain disorder v3.79 COQ7 Achchuthan Shanmugasundram Classified gene: COQ7 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.79 COQ7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS review.
Hereditary neuropathy or pain disorder v3.79 COQ7 Achchuthan Shanmugasundram Gene: coq7 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.78 COQ7 Achchuthan Shanmugasundram Phenotypes for gene: COQ7 were changed from autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9) to Neuronopathy, distal hereditary motor, autosomal recessive 9, OMIM:620402
Hereditary neuropathy or pain disorder v3.77 COQ7 Achchuthan Shanmugasundram Publications for gene: COQ7 were set to PMID: 36758993; 37077559
Hereditary neuropathy or pain disorder v3.76 COQ7 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: COQ7.
Tag Q1_24_NHS_review tag was added to gene: COQ7.
Hereditary neuropathy or pain disorder v3.76 COQ7 Achchuthan Shanmugasundram changed review comment from: PMID:36454683 reported three siblings of Portuguese decent with distal hereditary motor neuropathy and identified with a homozygous COQ7 variant that disrupted the start codon of the main COQ7 isoform 1 (c.3G-T).

PMID:36758993 reported two unrelated males of Chinese decent, who developed slowly progressive distal muscle weakness and atrophy at 14 to 15 years of age. They were identified with compound heterozygous variants in COQ7 gene (family 1: c.253-2A-T/ p.Leu156Gln & c.467T-A/ p.Leu156Gln; family 2: c.160C-T/ p.Arg54Trp & c.467T-G/ p.Leu156Arg).

PMID:3707755 reported three siblings of Syrian decent who presented with progressive distal limb muscle weakness and atrophy due to a length-dependent peripheral motor neuropathy. They were identified with a homozygous COQ7 variant (c.1A-G).

This gene has been associated with relevant phenotype in OMIM (MIM #620402), but not in Gene2Phenotype.; to: PMID:36454683 reported three siblings of Portuguese decent with distal hereditary motor neuropathy and identified with a homozygous COQ7 variant that disrupted the start codon of the main COQ7 isoform 1 (c.3G-T).

PMID:36758993 reported two unrelated males of Chinese decent, who developed slowly progressive distal muscle weakness and atrophy at 14 to 15 years of age. They were identified with compound heterozygous variants in COQ7 gene (family 1: c.253-2A-T/ p.Leu156Gln & c.467T-A/ p.Leu156Gln; family 2: c.160C-T/ p.Arg54Trp & c.467T-G/ p.Leu156Arg).

PMID:37077559 reported three siblings of Syrian decent who presented with progressive distal limb muscle weakness and atrophy due to a length-dependent peripheral motor neuropathy. They were identified with a homozygous COQ7 variant (c.1A-G).

This gene has been associated with relevant phenotype in OMIM (MIM #620402), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.76 COQ7 Achchuthan Shanmugasundram edited their review of gene: COQ7: Changed publications to: 36454683, 36758993, 37077559
Hereditary neuropathy or pain disorder v3.76 COQ7 Achchuthan Shanmugasundram reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: None; Publications: 36454683, 36758993, 3707755; Phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 9, OMIM:620402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.48 MGP Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there is sufficient evidence available (two unrelated cased and functional studies) for the association of monoallelic MGP variants with spondyloepiphyseal dysplasia, the MOI should be updated from 'BIALLELIC, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Skeletal dysplasia v4.48 MGP Achchuthan Shanmugasundram Mode of inheritance for gene: MGP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.47 MGP Achchuthan Shanmugasundram Phenotypes for gene: MGP were changed from Keutel syndrome 245150; Keutel syndrome 245150 to Keutel syndrome, OMIM:245150; spondyloepiphyseal dysplasia, MONDO:0016761
Skeletal dysplasia v4.46 MGP Achchuthan Shanmugasundram Publications for gene: MGP were set to
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram Tag Q1_24_MOI tag was added to gene: MGP.
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram changed review comment from: PMID:37923733 reported four individuals from two unrelated families with two different heterozygous MGP variants affecting Cys 19 residue (family 1: p.Cys19Phe; family 2: p.Cys19Tyr) and with previously undescribed spondyloepiphyseal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. In addition, functional evidence from heterozygous ‘knock-in’ mice expressing Cys19Phe MGP recapitulate most of the skeletal anomalies observed in the affected individuals.; to: PMID:37923733 reported four individuals from two unrelated families with two different heterozygous MGP variants affecting Cys 19 residue (family 1: p.Cys19Phe; family 2: p.Cys19Tyr) and with previously undescribed spondyloepiphyseal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. In addition, functional evidence from heterozygous ‘knock-in’ mice expressing Cys19Phe MGP recapitulate most of the skeletal anomalies observed in the affected individuals.

Although phenotype caused by biallelic MGP variants are already reported in both OMIM (MIM #245150) and Gene2Phenotype, phenotype caused by monoallelic variants are not yet reported in either resources.
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram edited their review of gene: MGP: Changed phenotypes to: Keutel syndrome, OMIM:245150, spondyloepiphyseal dysplasia, MONDO:0016761
Skeletal dysplasia v4.45 MGP Achchuthan Shanmugasundram reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 37923733; Phenotypes: spondyloepiphyseal dysplasia, MONDO:0016761; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.409 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850 to Hyperprolinemia, type I, OMIM:239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850
Early onset or syndromic epilepsy v4.152 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; hyperprolinemia type 1, MONDO:0009400 to Hyperprolinemia, type I, OMIM:239500; hyperprolinemia type 1, MONDO:0009400
Likely inborn error of metabolism v4.123 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; hyperprolinemia type 1, MONDO:0009400 to Hyperprolinemia, type I, OMIM:239500; hyperprolinemia type 1, MONDO:0009400
Undiagnosed metabolic disorders v1.610 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; hyperprolinemia type 1, MONDO:0009400 to Hyperprolinemia, type I, OMIM:239500; hyperprolinemia type 1, MONDO:0009400
Hypogonadotropic hypogonadism v1.41 KISS1R Arina Puzriakova Phenotypes for gene: KISS1R were changed from Hypogonadotropic hypogonadism 8 with or without anosmia, 614837; Precocious puberty, central, 1, (AD), 176400 to Hypogonadotropic hypogonadism 8 with or without anosmia, OMIM:614837; ?Precocious puberty, central, 1, OMIM:176400
Hypogonadotropic hypogonadism (GMS) v3.15 KISS1R Arina Puzriakova Phenotypes for gene: KISS1R were changed from Hypogonadotropic hypogonadism type 8 (OMIM 614837) to Hypogonadotropic hypogonadism 8 with or without anosmia, OMIM:614837
Palmoplantar keratoderma and erythrokeratodermas v1.30 KRT17 Arina Puzriakova Phenotypes for gene: KRT17 were changed from Pachyonychia Congenita, Type 2; Pachyonychia congenita, Jackson-Lawler type, 167210; Steatocystoma multiplex, 184500 to Pachyonychia congenita 2, OMIM:167210; Steatocystoma multiplex, OMIM:184500
Familial hidradenitis suppurativa v1.4 KRT17 Arina Puzriakova Phenotypes for gene: KRT17 were changed from Pachyonychia congenita 2, 167210; pachyonychia congenita with hidradenitis suppurativa to Pachyonychia congenita 2, OMIM:167210; Pachyonychia congenita with hidradenitis suppurativa
Non-syndromic hypotrichosis v1.13 KRT74 Arina Puzriakova Phenotypes for gene: KRT74 were changed from hypotrichosis simplex of the scalp; Hypotrichosis 3, 613981; HYPT3 to Hypotrichosis 3, OMIM:613981; HYPT3
Ectodermal dysplasia v3.23 KRT74 Arina Puzriakova Phenotypes for gene: KRT74 were changed from Pure hair and nail ectodermal dysplasia (PHNED) Ectodermal dysplasia 7, hair/nail type 614929; hypotrichosis simplex of the scalp; Hypotrichosis 3, 613981; HYPT3 to Woolly hair, autosomal dominant, OMIM:194300 (AD); ?Hypotrichosis 3, OMIM:613981 (AD); ?Ectodermal dysplasia 7, hair/nail type, OMIM:614929 (AR)
Ectodermal dysplasia without a known gene mutation v1.27 KRT74 Arina Puzriakova Phenotypes for gene: KRT74 were changed from Pure hair and nail ectodermal dysplasia (PHNED) Ectodermal dysplasia 7, hair/nail type 614929 to Woolly hair, autosomal dominant, OMIM:194300 (AD); ?Hypotrichosis 3, OMIM:613981 (AD); ?Ectodermal dysplasia 7, hair/nail type, OMIM:614929 (AR)
Ectodermal dysplasia without a known gene mutation v1.26 KRT74 Arina Puzriakova Classified gene: KRT74 as Green List (high evidence)
Ectodermal dysplasia without a known gene mutation v1.26 KRT74 Arina Puzriakova Gene: krt74 has been classified as Green List (High Evidence).
Ectodermal dysplasia without a known gene mutation v1.25 KRT74 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from biallelic to monoallelic inline with MOI on equivalent GMS panel (R163 Ectodermal dysplasia v3.0).

"This gene is Green on the Non-syndromic hypotrichosis panel (version 1.1, code 189) with a monoallelic mode of inheritance for Hypotrichosis. It has a Red rating with a biallelic mode of inheritance on the Ectodermal dysplasia without a known gene mutation panel (version 1.15, code 136), for Ectodermal dysplasia 7 due to one family report (PMID: 24714551). Therefore for the Green status, a monoallelic mode of inheritance is given here."
Ectodermal dysplasia without a known gene mutation v1.25 KRT74 Arina Puzriakova Mode of inheritance for gene: KRT74 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy v1.476 MME Arina Puzriakova changed review comment from: Comment on mode of inheritance: Updating from 'biallelic' to 'both mono- and biallelic' inline with MOI on equivalent GMS panel (R78 Hereditary neuropathy or pain disorder).

"Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype"; to: Comment on mode of inheritance: Updating from 'biallelic' to 'both mono- and biallelic' inline with MOI on equivalent GMS panel (R78 Hereditary neuropathy or pain disorder v3.24).

"Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype"
Ectodermal dysplasia v3.22 KRT74 Arina Puzriakova Tag watchlist_moi tag was added to gene: KRT74.
Hereditary neuropathy v1.476 MME Arina Puzriakova Added comment: Comment on mode of inheritance: Updating from 'biallelic' to 'both mono- and biallelic' inline with MOI on equivalent GMS panel (R78 Hereditary neuropathy or pain disorder).

"Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype"
Hereditary neuropathy v1.476 MME Arina Puzriakova Mode of inheritance for gene: MME was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v3.129 MYLK Arina Puzriakova Phenotypes for gene: MYLK were changed from Megacystis Microcolon Intestinal Hypoperistalsis Syndrome; MMIH to Megacystis-microcolon-intestinal hypoperistalsis syndrome 1, OMIM:249210
Thoracic aortic aneurysm or dissection v1.127 MYLK Arina Puzriakova Phenotypes for gene: MYLK were changed from Aortic aneurysm, familial thoracic 7, 613780; Aortic aneurysm, familial thoracic 7 (613780) to Aortic aneurysm, familial thoracic 7, OMIM:613780
Thoracic aortic aneurysm or dissection (GMS) v3.8 MYLK Arina Puzriakova Phenotypes for gene: MYLK were changed from Aortic aneurysm, familial thoracic 7 (613780); Aortic aneurysm, familial thoracic 7, 613780 to Aortic aneurysm, familial thoracic 7, OMIM:613780
Amyotrophic lateral sclerosis/motor neuron disease v1.69 OPTN Arina Puzriakova Added comment: Comment on publications: PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."
PMID: 26503823
PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS
(ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS
(iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient
and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."
PMID: 26203661
PMID: 25943890
PMID: 25859013 - functional evidence
PMID: 25681989
Amyotrophic lateral sclerosis/motor neuron disease v1.69 OPTN Arina Puzriakova Publications for gene: OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890; PMID: 25859013 - functional evidence; PMID: 25681989
Amyotrophic lateral sclerosis/motor neuron disease v1.68 OPTN Arina Puzriakova Phenotypes for gene: OPTN were changed from Amyotrophic Lateral Sclerosis, Recessive; Glaucoma 1, open angle, E, 137760 to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia, OMIM:613435
Structural eye disease v3.73 OPTN Arina Puzriakova Phenotypes for gene: OPTN were changed from Glaucoma 1, open angle, E, 137760; {Glaucoma, normal tension, susceptibility to} 606657 to Glaucoma 1, open angle, E, OMIM:137760; {Glaucoma, normal tension, susceptibility to}, OMIM:606657; Adult-onset
Glaucoma (developmental) v1.43 OPTN Arina Puzriakova Phenotypes for gene: OPTN were changed from Glaucoma 1, open angle, E 137760; {Glaucoma, normal tension, susceptibility to} 606657 to Glaucoma 1, open angle, E, OMIM:137760; {Glaucoma, normal tension, susceptibility to}, OMIM:606657; Adult-onset
Early onset or syndromic epilepsy v4.151 PRICKLE1 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

ClinGen have classified PRICKLE1-related AR PME as LIMITED (18 Aug 2020) and AD epilepsy as DISPUTED (01 Sept 2020).

There are reports in the literature of both homozygous (PMID: 30564977; 30345727) and heterozygous cases (PMID: 21276947; 26727662; 29790814; 31875159; 31035234); however, most variants are missense with little further supportive evidence. Founder effect has been suggested for one recurrent homozygous variant (PMID: 15634728; 15642921; 16376507; 18976727) and reports of unaffected carriers should also be considered (PMID: 31035234).

GeneReview for PRICKLE1-Related Disorders - PMID: 20301774

ClinVar entries are all VUS/LB/B and all variants identified in Genomics England's Clinical Variant Archive (CVA) dataset to date are UNCLASSIFIED.; to: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

ClinGen have classified PRICKLE1-related AR PME as LIMITED (18 Aug 2020) and AD epilepsy as DISPUTED (01 Sept 2020).

There are reports in the literature of both homozygous (PMID: 30564977; 30345727) and heterozygous cases (PMID: 21276947; 26727662; 29790814; 31875159; 31035234); however, most variants are missense with little further supportive evidence. Founder effect has been suggested for one recurrent homozygous variant (PMID: 15634728; 15642921; 16376507; 18976727) and reports of unaffected carriers should also be considered (PMID: 31035234).

GeneReview for PRICKLE1-Related Disorders - PMID: 20301774

ClinVar entries are all VUS/LB/B and all variants identified to date in Genomics England's Clinical Variant Archive (CVA) dataset are UNCLASSIFIED.
Early onset or syndromic epilepsy v4.151 PRICKLE1 Arina Puzriakova changed review comment from: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

ClinGen have classified PRICKLE1-related AR PME as LIMITED (18 Aug 2020) and AD epilepsy as DISPUTED (01 Sept 2020).

There are reports in the literature of both homozygous (PMID: 30564977; 30345727) and heterozygous cases (PMID: 21276947; 26727662; 29790814; 31875159; 31035234); however, most variants are missense with little further supportive evidence. Founder effect has been suggested for one recurrent homozygous variants (PMID: 15634728; 15642921; 16376507; 18976727) and reports of unaffected carriers should be considered (PMID: 31035234).

GeneReview for PRICKLE1-Related Disorders - PMID: 20301774

ClinVar entries are all VUS/LB/B and all variants identified in Genomics England's Clinical Variant Archive (CVA) dataset to date are UNCLASSIFIED.; to: Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.

ClinGen have classified PRICKLE1-related AR PME as LIMITED (18 Aug 2020) and AD epilepsy as DISPUTED (01 Sept 2020).

There are reports in the literature of both homozygous (PMID: 30564977; 30345727) and heterozygous cases (PMID: 21276947; 26727662; 29790814; 31875159; 31035234); however, most variants are missense with little further supportive evidence. Founder effect has been suggested for one recurrent homozygous variant (PMID: 15634728; 15642921; 16376507; 18976727) and reports of unaffected carriers should also be considered (PMID: 31035234).

GeneReview for PRICKLE1-Related Disorders - PMID: 20301774

ClinVar entries are all VUS/LB/B and all variants identified in Genomics England's Clinical Variant Archive (CVA) dataset to date are UNCLASSIFIED.
Early onset or syndromic epilepsy v4.151 PRICKLE1 Arina Puzriakova Publications for gene: PRICKLE1 were set to 18976727; 21276947
Early onset or syndromic epilepsy v4.150 PRICKLE1 Arina Puzriakova edited their review of gene: PRICKLE1: Changed publications to: 30564977, 30345727, 21276947, 26727662, 29790814, 31875159, 31035234, 15634728, 15642921, 16376507, 18976727, 20301774