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Arthrogryposis v0.602 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Arthrogryposis v0.602 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, MIM# 613150
Mendeliome v1.3620 KCNE5 Chirag Patel Phenotypes for gene: KCNE5 were changed from Atrial fibrillation to Atrial fibrillation; Brugada syndrome, MONDO:0015263
Arthrogryposis v0.601 POMT2 Zornitza Stark Publications for gene: POMT2 were set to
Mendeliome v1.3619 Chirag Patel Added reviews for gene KCNE5 from panel Brugada syndrome
Arthrogryposis v0.600 POMT2 Zornitza Stark Mode of inheritance for gene: POMT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.599 POMT2 Zornitza Stark reviewed gene: POMT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19138766; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, MIM# 613150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brugada syndrome v0.43 KCNE5 Chirag Patel Marked gene: KCNE5 as ready
Brugada syndrome v0.43 KCNE5 Chirag Patel Gene: kcne5 has been classified as Red List (Low Evidence).
Brugada syndrome v0.43 HCN4 Chirag Patel Marked gene: HCN4 as ready
Brugada syndrome v0.43 HCN4 Chirag Patel Gene: hcn4 has been classified as Red List (Low Evidence).
Brugada syndrome v0.43 ANK2 Chirag Patel Marked gene: ANK2 as ready
Brugada syndrome v0.43 ANK2 Chirag Patel Gene: ank2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.43 PKP2 Chirag Patel gene: PKP2 was added
gene: PKP2 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: PKP2.
Mode of inheritance for gene: PKP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PKP2 were set to Brugada syndrome, MONDO:0015263
Review for gene: PKP2 was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.43 SLMAP Chirag Patel gene: SLMAP was added
gene: SLMAP was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: SLMAP.
Mode of inheritance for gene: SLMAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLMAP were set to Brugada syndrome, MONDO:0015263
Review for gene: SLMAP was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.43 SCN2B Chirag Patel gene: SCN2B was added
gene: SCN2B was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: SCN2B.
Mode of inheritance for gene: SCN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCN2B were set to Brugada syndrome, MONDO:0015263
Review for gene: SCN2B was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.43 TRPM4 Chirag Patel gene: TRPM4 was added
gene: TRPM4 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: TRPM4.
Mode of inheritance for gene: TRPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRPM4 were set to Brugada syndrome, MONDO:0015263
Review for gene: TRPM4 was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.42 KCNE5 Chirag Patel gene: KCNE5 was added
gene: KCNE5 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: KCNE5.
Mode of inheritance for gene: KCNE5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNE5 were set to Brugada syndrome, MONDO:0015263
Review for gene: KCNE5 was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.42 HCN4 Chirag Patel gene: HCN4 was added
gene: HCN4 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: HCN4.
Mode of inheritance for gene: HCN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HCN4 were set to Brugada syndrome, MONDO:0015263
Review for gene: HCN4 was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.42 ANK2 Chirag Patel gene: ANK2 was added
gene: ANK2 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: ANK2.
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ANK2 were set to Brugada syndrome, MONDO:0015263
Review for gene: ANK2 was set to RED
Added comment: ClinGen DISPUTED - Nov 2017
Sources: ClinGen
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.41 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.40 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.40 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from Brugada syndrome, MONDO:0015263 to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.40 KCNE3 Chirag Patel Phenotypes for gene: KCNE3 were changed from to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.39 CACNA2D1 Chirag Patel Phenotypes for gene: CACNA2D1 were changed from to Brugada syndrome 1, MONDO:0011001
Brugada syndrome v0.38 KCNJ8 Chirag Patel Phenotypes for gene: KCNJ8 were changed from Brugada syndrome 1, MONDO:0011001 to Brugada syndrome 1, MONDO:0011001
Brugada syndrome v0.38 KCNJ8 Chirag Patel Phenotypes for gene: KCNJ8 were changed from Brugada syndrome to Brugada syndrome 1, MONDO:0011001
Brugada syndrome v0.37 SCN1B Chirag Patel Phenotypes for gene: SCN1B were changed from Brugada syndrome 1, MONDO:0011001 to Brugada syndrome 1, MONDO:0011001
Brugada syndrome v0.37 SCN1B Chirag Patel Phenotypes for gene: SCN1B were changed from to Brugada syndrome 1, MONDO:0011001
Mendeliome v1.3618 PLAT Chirag Patel Marked gene: PLAT as ready
Mendeliome v1.3618 PLAT Chirag Patel Gene: plat has been classified as Red List (Low Evidence).
Mendeliome v1.3618 TP53BP2 Chirag Patel Marked gene: TP53BP2 as ready
Mendeliome v1.3618 TP53BP2 Chirag Patel Gene: tp53bp2 has been classified as Red List (Low Evidence).
Mendeliome v1.3618 TP53BP2 Chirag Patel gene: TP53BP2 was added
gene: TP53BP2 was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: TP53BP2.
Mode of inheritance for gene: TP53BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53BP2 were set to Open-angle glaucoma MONDO:0005338
Review for gene: TP53BP2 was set to RED
Added comment: ClinGen DISPUTED - May 2023
Sources: ClinGen
Mendeliome v1.3617 Chirag Patel Copied gene PLAT from panel Bleeding and Platelet Disorders
Mendeliome v1.3617 PLAT Chirag Patel gene: PLAT was added
gene: PLAT was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PLAT were set to Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Bleeding and Platelet Disorders v1.63 PLAT Chirag Patel Marked gene: PLAT as ready
Bleeding and Platelet Disorders v1.63 PLAT Chirag Patel Gene: plat has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.63 PLAT Chirag Patel gene: PLAT was added
gene: PLAT was added to Bleeding and Platelet Disorders. Sources: ClinGen
disputed tags were added to gene: PLAT.
Mode of inheritance for gene: PLAT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PLAT were set to Thrombophilia, familial, due to decreased release of tissue plasminogen activator MONDO:0012872
Review for gene: PLAT was set to RED
Added comment: ClinGen DISPUTED - Jun 2023
Sources: ClinGen
Oligodontia v0.32 MSX1 Chirag Patel Phenotypes for gene: MSX1 were changed from Tooth agenesis, selective, 1, MONDO:0007129 to Tooth agenesis, selective, 1, MONDO:0007129
Oligodontia v0.32 MSX1 Chirag Patel Phenotypes for gene: MSX1 were changed from Tooth agenesis, selective, 1, MONDO:0007129 to Tooth agenesis, selective, 1, MONDO:0007129
Oligodontia v0.32 MSX1 Chirag Patel Phenotypes for gene: MSX1 were changed from to Tooth agenesis, selective, 1, MONDO:0007129
Oligodontia v0.31 MSX1 Chirag Patel reviewed gene: MSX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tooth agenesis, selective, 1, MONDO:0007129; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Oligodontia v0.31 Chirag Patel Added reviews for gene MSX1 from panel Mendeliome
Ectodermal Dysplasia v0.103 Chirag Patel Added reviews for gene MSX1 from panel Mendeliome
Clefting disorders v0.282 Chirag Patel Added reviews for gene MSX1 from panel Mendeliome
Mendeliome v1.3616 ACADL Chirag Patel Phenotypes for gene: ACADL were changed from Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related to Long chain acyl-CoA dehydrogenase deficiency MONDO:0020531
Mendeliome v1.3615 Chirag Patel Added reviews for gene ACADL from panel Fatty Acid Oxidation Defects
Fatty Acid Oxidation Defects v1.15 ACADL Chirag Patel Phenotypes for gene: ACADL were changed from Pulmonary surfactant dysfunction to Long chain acyl-CoA dehydrogenase deficiency MONDO:0020531
Fatty Acid Oxidation Defects v1.14 ACADL Chirag Patel reviewed gene: ACADL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Long chain acyl-CoA dehydrogenase deficiency MONDO:0020531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.52 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Red cell disorders v1.38 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Anaemia, hypochromic microcytic, with iron overload 2 MIM# 615234 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Mendeliome v1.3614 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Mendeliome v1.3614 STEAP3 Chirag Patel Phenotypes for gene: STEAP3 were changed from Anaemia, hypochromic microcytic, with iron overload 2, MIM# 615234 to Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094
Mendeliome v1.3613 STEAP3 Chirag Patel Tag disputed tag was added to gene: STEAP3.
Red cell disorders v1.37 Chirag Patel Added reviews for gene STEAP3 from panel Metal Metabolism Disorders
Mendeliome v1.3613 Chirag Patel Added reviews for gene STEAP3 from panel Metal Metabolism Disorders
Red cell disorders v1.36 STEAP3 Chirag Patel Tag disputed tag was added to gene: STEAP3.
Metal Metabolism Disorders v0.51 STEAP3 Chirag Patel Tag disputed tag was added to gene: STEAP3.
Metal Metabolism Disorders v0.51 STEAP3 Chirag Patel reviewed gene: STEAP3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe congenital hypochromic anemia with ringed sideroblasts, MONDO:0014094; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3612 FOXD3 Chirag Patel Phenotypes for gene: FOXD3 were changed from Autoimmune disease, susceptibility to, 1 MONDO:0011919 to Autoimmune disease, susceptibility to, 1 MONDO:0011919; Aniridia, MONDO:0019172
Mendeliome v1.3611 FOXD3 Chirag Patel Deleted their review
Mendeliome v1.3611 Chirag Patel Added reviews for gene FOXD3 from panel Eye Anterior Segment Abnormalities
Eye Anterior Segment Abnormalities v1.17 FOXD3 Chirag Patel Marked gene: FOXD3 as ready
Eye Anterior Segment Abnormalities v1.17 FOXD3 Chirag Patel Gene: foxd3 has been classified as Red List (Low Evidence).
Eye Anterior Segment Abnormalities v1.17 FOXD3 Chirag Patel gene: FOXD3 was added
gene: FOXD3 was added to Eye Anterior Segment Abnormalities. Sources: ClinGen
disputed tags were added to gene: FOXD3.
Mode of inheritance for gene: FOXD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FOXD3 were set to Aniridia, MONDO:0019172
Review for gene: FOXD3 was set to RED
Added comment: ClinGen DISPUTED - Dec 2022
Sources: ClinGen
Mendeliome v1.3610 Chirag Patel Added reviews for gene PRKACG from panel Bleeding and Platelet Disorders
Mendeliome v1.3609 PRKACG Chirag Patel Tag disputed tag was added to gene: PRKACG.
Bleeding and Platelet Disorders v1.62 PRKACG Chirag Patel Tag disputed tag was added to gene: PRKACG.
Bleeding and Platelet Disorders v1.62 PRKACG Chirag Patel reviewed gene: PRKACG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v1.19 VCL Chirag Patel Phenotypes for gene: VCL were changed from Cardiomyopathy, hypertrophic, 15, MIM# 613255 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 VCL Chirag Patel Tag disputed tag was added to gene: VCL.
Hypertrophic cardiomyopathy_HCM v1.18 VCL Chirag Patel reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.18 TRIM63 Chirag Patel changed review comment from: ClinGen DISPUTED - Oct 2022; to: AD HCM ClinGen DISPUTED - Oct 2022
Hypertrophic cardiomyopathy_HCM v1.18 TRIM63 Chirag Patel reviewed gene: TRIM63: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel reviewed gene: MYPN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.18 MYPN Chirag Patel Phenotypes for gene: MYPN were changed from Cardiomyopathy, hypertrophic, 22 (MIM# 615248) to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.17 MYPN Chirag Patel Tag disputed tag was added to gene: MYPN.
Mendeliome v1.3609 MYOZ2 Chirag Patel Phenotypes for gene: MYOZ2 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3609 MYOZ2 Chirag Patel Phenotypes for gene: MYOZ2 were changed from Cardiomyopathy, hypertrophic, 16 MIM#613838 to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3608 MYOZ2 Chirag Patel Tag disputed tag was added to gene: MYOZ2.
Mendeliome v1.3608 Chirag Patel Added reviews for gene MYOZ2 from panel Hypertrophic cardiomyopathy_HCM
Hypertrophic cardiomyopathy_HCM v1.17 MYOZ2 Chirag Patel reviewed gene: MYOZ2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.17 MYOZ2 Chirag Patel Phenotypes for gene: MYOZ2 were changed from Cardiomyopathy, hypertrophic, 16 MIM#613838 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.16 MYOZ2 Chirag Patel Tag disputed tag was added to gene: MYOZ2.
Mendeliome v1.3607 MYOM1 Chirag Patel Tag disputed tag was added to gene: MYOM1.
Mendeliome v1.3607 Chirag Patel Added reviews for gene MYOM1 from panel Hypertrophic cardiomyopathy_HCM
Hypertrophic cardiomyopathy_HCM v1.16 MYOM1 Chirag Patel Tag disputed tag was added to gene: MYOM1.
Hypertrophic cardiomyopathy_HCM v1.16 MYOM1 Chirag Patel reviewed gene: MYOM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.16 KCNQ1 Chirag Patel Marked gene: KCNQ1 as ready
Hypertrophic cardiomyopathy_HCM v1.16 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v1.16 KCNQ1 Chirag Patel gene: KCNQ1 was added
gene: KCNQ1 was added to Hypertrophic cardiomyopathy_HCM. Sources: ClinGen
disputed tags were added to gene: KCNQ1.
Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNQ1 were set to Hypertrophic cardiomyopathy, MONDO:0005045
Review for gene: KCNQ1 was set to RED
Added comment: ClinGen DISPUTED - May 2022
Sources: ClinGen
Mendeliome v1.3606 MYLK2 Chirag Patel Tag disputed tag was added to gene: MYLK2.
Mendeliome v1.3606 Chirag Patel Added reviews for gene MYLK2 from panel Hypertrophic cardiomyopathy_HCM
Hypertrophic cardiomyopathy_HCM v1.15 MYLK2 Chirag Patel Tag disputed tag was added to gene: MYLK2.
Hypertrophic cardiomyopathy_HCM v1.15 MYLK2 Chirag Patel reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.15 MYH6 Chirag Patel Phenotypes for gene: MYH6 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.15 MYH6 Chirag Patel Phenotypes for gene: MYH6 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.15 MYH6 Chirag Patel Phenotypes for gene: MYH6 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.15 MYH6 Chirag Patel Phenotypes for gene: MYH6 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.15 MYH6 Chirag Patel Phenotypes for gene: MYH6 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.14 MYH6 Chirag Patel Tag disputed tag was added to gene: MYH6.
Hypertrophic cardiomyopathy_HCM v1.14 MYH6 Chirag Patel reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.14 DSP Chirag Patel Marked gene: DSP as ready
Hypertrophic cardiomyopathy_HCM v1.14 DSP Chirag Patel Gene: dsp has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v1.14 DSP Chirag Patel gene: DSP was added
gene: DSP was added to Hypertrophic cardiomyopathy_HCM. Sources: ClinGen
disputed tags were added to gene: DSP.
Mode of inheritance for gene: DSP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DSP were set to Hypertrophic cardiomyopathy, MONDO:0005045
Review for gene: DSP was set to RED
Added comment: ClinGen DISPUTED - Jun 2022
Sources: ClinGen
Hypertrophic cardiomyopathy_HCM v1.13 CASQ2 Chirag Patel Marked gene: CASQ2 as ready
Hypertrophic cardiomyopathy_HCM v1.13 CASQ2 Chirag Patel Gene: casq2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v1.13 CASQ2 Chirag Patel gene: CASQ2 was added
gene: CASQ2 was added to Hypertrophic cardiomyopathy_HCM. Sources: ClinGen
disputed tags were added to gene: CASQ2.
Mode of inheritance for gene: CASQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CASQ2 were set to Hypertrophic cardiomyopathy, MONDO:0005045
Review for gene: CASQ2 was set to RED
Added comment: ClinGen DISPUTED - May 2022
Sources: ClinGen
Mendeliome v1.3605 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.12 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Mendeliome v1.3604 CALR3 Chirag Patel Tag refuted was removed from gene: CALR3.
Tag disputed tag was added to gene: CALR3.
Mendeliome v1.3604 Chirag Patel Added reviews for gene CALR3 from panel Hypertrophic cardiomyopathy_HCM
Hypertrophic cardiomyopathy_HCM v1.13 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.12 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.12 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from d) Hypertrophic cardiomyopathy, MONDO:0005045 to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.12 CALR3 Chirag Patel Phenotypes for gene: CALR3 were changed from Hypertrophic cardiomyopathy to d) Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.11 CALR3 Chirag Patel Tag refuted was removed from gene: CALR3.
Tag disputed tag was added to gene: CALR3.
Hypertrophic cardiomyopathy_HCM v1.11 CALR3 Chirag Patel reviewed gene: CALR3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3603 ANKRD1 Chirag Patel Tag disputed tag was added to gene: ANKRD1.
Mendeliome v1.3603 ANKRD1 Chirag Patel reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v1.11 ANKRD1 Chirag Patel Phenotypes for gene: ANKRD1 were changed from hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v1.10 ANKRD1 Chirag Patel reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v1.10 ANKRD1 Chirag Patel Tag disputed tag was added to gene: ANKRD1.
Incidentalome v0.368 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.368 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.368 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.368 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.368 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.368 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.368 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.368 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.368 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.368 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.367 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.367 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.367 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.367 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Incidentalome v0.367 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Incidentalome v0.367 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Mendeliome v1.3603 Chirag Patel Copied gene KCNE2 from panel Long QT Syndrome
Mendeliome v1.3603 KCNE2 Chirag Patel gene: KCNE2 was added
gene: KCNE2 was added to Mendeliome. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: KCNE2.
Mode of inheritance for gene: KCNE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNE2 were set to 31983240; 28794082
Phenotypes for gene: KCNE2 were set to Long QT syndrome
Incidentalome v0.367 Chirag Patel Added reviews for gene KCNE2 from panel Long QT Syndrome
Incidentalome v0.366 KCNE2 Chirag Patel Tag disputed tag was added to gene: KCNE2.
Long QT Syndrome v0.62 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Long QT Syndrome v0.62 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.62 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Long QT Syndrome v0.62 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.62 KCNE2 Chirag Patel Classified gene: KCNE2 as Red List (low evidence)
Long QT Syndrome v0.62 KCNE2 Chirag Patel Gene: kcne2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.61 KCNE2 Chirag Patel Tag disputed tag was added to gene: KCNE2.
Long QT Syndrome v0.61 KCNE2 Chirag Patel reviewed gene: KCNE2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome MONDO:0002442; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.366 ANK2 Chirag Patel Tag disputed tag was added to gene: ANK2.
Mendeliome v1.3602 Chirag Patel Copied gene AKAP9 from panel Long QT Syndrome
Mendeliome v1.3602 AKAP9 Chirag Patel gene: AKAP9 was added
gene: AKAP9 was added to Mendeliome. Sources: Expert Review Red,Victorian Clinical Genetics Services
disputed tags were added to gene: AKAP9.
Mode of inheritance for gene: AKAP9 was set to Unknown
Publications for gene: AKAP9 were set to 31983240
Phenotypes for gene: AKAP9 were set to long QT syndrome
Mendeliome v1.3601 TUBA8 Chirag Patel Deleted their review
Mendeliome v1.3601 TUBA8 Chirag Patel Deleted their comment
Mendeliome v1.3601 Chirag Patel Added reviews for gene TUBA8 from panel Polymicrogyria and Schizencephaly
Fetal anomalies v1.470 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Intellectual disability syndromic and non-syndromic v1.429 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Fetal anomalies v1.470 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.429 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Callosome v0.569 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Callosome v0.569 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v1.277 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Genetic Epilepsy v1.277 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebellar and Pontocerebellar Hypoplasia v1.91 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Cerebellar and Pontocerebellar Hypoplasia v1.91 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Tubulinopathies v1.2 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Tubulinopathies v1.2 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Polymicrogyria and Schizencephaly v0.201 TUBA8 Chirag Patel Tag disputed tag was added to gene: TUBA8.
Polymicrogyria and Schizencephaly v0.201 TUBA8 Chirag Patel reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3600 Chirag Patel Copied gene TEKT1 from panel Ciliary Dyskinesia
Mendeliome v1.3600 TEKT1 Chirag Patel gene: TEKT1 was added
gene: TEKT1 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: TEKT1.
Mode of inheritance for gene: TEKT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TEKT1 were set to Primary ciliary dyskinesia, MONDO:0016575
Ciliary Dyskinesia v1.66 TEKT1 Chirag Patel Marked gene: TEKT1 as ready
Ciliary Dyskinesia v1.66 TEKT1 Chirag Patel Gene: tekt1 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v1.66 TEKT1 Chirag Patel gene: TEKT1 was added
gene: TEKT1 was added to Ciliary Dyskinesia. Sources: ClinGen
disputed tags were added to gene: TEKT1.
Mode of inheritance for gene: TEKT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TEKT1 were set to Primary ciliary dyskinesia, MONDO:0016575
Review for gene: TEKT1 was set to RED
Added comment: ClinGen DISPUTED - Mar 2025
Sources: ClinGen
Mendeliome v1.3599 DNAH14 Chirag Patel changed review comment from: ClinGen DISPUTED - May 2025
Sources: ClinGen; to: PCD - ClinGen DISPUTED - May 2025
Sources: ClinGen
Mendeliome v1.3599 Chirag Patel Added reviews for gene DNAH14 from panel Ciliary Dyskinesia
Ciliary Dyskinesia v1.65 DNAH14 Chirag Patel Marked gene: DNAH14 as ready
Ciliary Dyskinesia v1.65 DNAH14 Chirag Patel Gene: dnah14 has been classified as Red List (Low Evidence).
Mendeliome v1.3598 AK7 Chirag Patel Marked gene: AK7 as ready
Mendeliome v1.3598 AK7 Chirag Patel Gene: ak7 has been classified as Red List (Low Evidence).
Fetal anomalies v1.470 DNAH6 Chirag Patel Tag disputed tag was added to gene: DNAH6.
Heterotaxy v1.44 DNAH6 Chirag Patel Tag disputed tag was added to gene: DNAH6.
Ciliary Dyskinesia v1.65 DNAH6 Chirag Patel Tag disputed tag was added to gene: DNAH6.
Ciliary Dyskinesia v1.65 DNAH14 Chirag Patel gene: DNAH14 was added
gene: DNAH14 was added to Ciliary Dyskinesia. Sources: ClinGen
disputed tags were added to gene: DNAH14.
Mode of inheritance for gene: DNAH14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAH14 were set to Primary ciliary dyskinesia, MONDO:0016575
Review for gene: DNAH14 was set to RED
Added comment: ClinGen DISPUTED - May 2025
Sources: ClinGen
Mendeliome v1.3598 Chirag Patel Copied gene AK7 from panel Ciliary Dyskinesia
Mendeliome v1.3598 AK7 Chirag Patel gene: AK7 was added
gene: AK7 was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: AK7.
Mode of inheritance for gene: AK7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AK7 were set to Primary ciliary dyskinesia, MONDO:0016575
Ciliary Dyskinesia v1.64 AK7 Chirag Patel Marked gene: AK7 as ready
Ciliary Dyskinesia v1.64 AK7 Chirag Patel Gene: ak7 has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v1.64 AK7 Chirag Patel gene: AK7 was added
gene: AK7 was added to Ciliary Dyskinesia. Sources: ClinGen
disputed tags were added to gene: AK7.
Mode of inheritance for gene: AK7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AK7 were set to Primary ciliary dyskinesia, MONDO:0016575
Review for gene: AK7 was set to RED
Added comment: ClinGen DISPUTED - Mar 2023
Sources: ClinGen
Vasculitis v0.95 FBN1 Chirag Patel Classified gene: FBN1 as Red List (low evidence)
Vasculitis v0.95 FBN1 Chirag Patel Gene: fbn1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.429 IGBP1 Chirag Patel Deleted their review
Intellectual disability syndromic and non-syndromic v1.429 IGBP1 Chirag Patel Deleted their comment
Intellectual disability syndromic and non-syndromic v1.429 IGBP1 Chirag Patel Tag disputed tag was added to gene: IGBP1.
Callosome v0.569 IGBP1 Chirag Patel Tag disputed tag was added to gene: IGBP1.
Intellectual disability syndromic and non-syndromic v1.429 IGBP1 Chirag Patel reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Callosome v0.569 IGBP1 Chirag Patel reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3597 IGBP1 Chirag Patel Tag disputed tag was added to gene: IGBP1.
Mendeliome v1.3597 IGBP1 Chirag Patel reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Vasculitis v0.94 FBN1 Chirag Patel Classified gene: FBN1 as Red List (low evidence)
Vasculitis v0.94 FBN1 Chirag Patel Gene: fbn1 has been classified as Red List (Low Evidence).
Vasculitis v0.94 FBN1 Chirag Patel Classified gene: FBN1 as Red List (low evidence)
Vasculitis v0.94 FBN1 Chirag Patel Gene: fbn1 has been classified as Red List (Low Evidence).
Mendeliome v1.3597 ARHGEF6 Chirag Patel Tag disputed tag was added to gene: ARHGEF6.
Vasculitis v0.93 FBN1 Chirag Patel reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3597 Chirag Patel Added reviews for gene ARHGEF6 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v1.429 ARHGEF6 Chirag Patel Tag disputed tag was added to gene: ARHGEF6.
Intellectual disability syndromic and non-syndromic v1.429 ARHGEF6 Chirag Patel reviewed gene: ARHGEF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-syndromic X-linked intellectual disability, MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arrhythmogenic Cardiomyopathy v0.74 TTN Chirag Patel Marked gene: TTN as ready
Arrhythmogenic Cardiomyopathy v0.74 TTN Chirag Patel Gene: ttn has been classified as Red List (Low Evidence).
Arrhythmogenic Cardiomyopathy v0.74 TTN Chirag Patel gene: TTN was added
gene: TTN was added to Arrhythmogenic Cardiomyopathy. Sources: ClinGen
disputed tags were added to gene: TTN.
Mode of inheritance for gene: TTN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TTN were set to Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Review for gene: TTN was set to RED
Added comment: ClinGen DISPUTED - Oct 2025
Sources: ClinGen
Brugada syndrome v0.36 KCNH2 Chirag Patel Marked gene: KCNH2 as ready
Brugada syndrome v0.36 KCNH2 Chirag Patel Gene: kcnh2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.36 ABCC9 Chirag Patel Marked gene: ABCC9 as ready
Brugada syndrome v0.36 ABCC9 Chirag Patel Gene: abcc9 has been classified as Red List (Low Evidence).
Brugada syndrome v0.36 ABCC9 Chirag Patel gene: ABCC9 was added
gene: ABCC9 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: ABCC9.
Mode of inheritance for gene: ABCC9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ABCC9 were set to Brugada syndrome, MONDO:0015263
Review for gene: ABCC9 was set to RED
Added comment: ClinGen DISPUTED - Oct 2025
Sources: ClinGen
Brugada syndrome v0.36 KCNH2 Chirag Patel gene: KCNH2 was added
gene: KCNH2 was added to Brugada syndrome. Sources: ClinGen
disputed tags were added to gene: KCNH2.
Mode of inheritance for gene: KCNH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNH2 were set to Brugada syndrome, MONDO:0015263
Review for gene: KCNH2 was set to RED
Added comment: ClinGen DISPUTED - Jun 2025
Sources: ClinGen
Mendeliome v1.3596 ANK2 Chirag Patel changed review comment from: ClinGen DISPUTED for catecholaminergic polymorphic ventricular tachycardia - Jan 2021
Sources: ClinGen; to: CPVT - ClinGen DISPUTED - Jan 2021
Sources: ClinGen
Mendeliome v1.3596 PKP2 Chirag Patel edited their review of gene: PKP2: Added comment: CPVT - ClinGen DISPUTED - Jan 2021; Changed phenotypes: Catecholaminergic polymorphic ventricular tachycardia, MONDO:0017990
Mendeliome v1.3596 ANK2 Chirag Patel changed review comment from: ClinGen DISPUTED - Jan 2021
Sources: ClinGen; to: ClinGen DISPUTED for catecholaminergic polymorphic ventricular tachycardia - Jan 2021
Sources: ClinGen
Mendeliome v1.3596 Chirag Patel Added reviews for gene ANK2 from panel Catecholaminergic Polymorphic Ventricular Tachycardia
Mendeliome v1.3595 Chirag Patel Added reviews for gene PKP2 from panel Catecholaminergic Polymorphic Ventricular Tachycardia
Catecholaminergic Polymorphic Ventricular Tachycardia v0.37 ANK2 Chirag Patel Marked gene: ANK2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.37 ANK2 Chirag Patel Gene: ank2 has been classified as Red List (Low Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.37 ANK2 Chirag Patel gene: ANK2 was added
gene: ANK2 was added to Catecholaminergic Polymorphic Ventricular Tachycardia. Sources: ClinGen
disputed tags were added to gene: ANK2.
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ANK2 were set to Catecholaminergic polymorphic ventricular tachycardia, MONDO:0017990
Review for gene: ANK2 was set to RED
Added comment: ClinGen DISPUTED - Jan 2021
Sources: ClinGen
Catecholaminergic Polymorphic Ventricular Tachycardia v0.36 PKP2 Chirag Patel Marked gene: PKP2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.36 PKP2 Chirag Patel Gene: pkp2 has been classified as Red List (Low Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.36 PKP2 Chirag Patel gene: PKP2 was added
gene: PKP2 was added to Catecholaminergic Polymorphic Ventricular Tachycardia. Sources: ClinGen
disputed tags were added to gene: PKP2.
Mode of inheritance for gene: PKP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PKP2 were set to Catecholaminergic polymorphic ventricular tachycardia, MONDO:0017990
Review for gene: PKP2 was set to RED
Added comment: ClinGen DISPUTED - Jan 2021
Sources: ClinGen
Catecholaminergic Polymorphic Ventricular Tachycardia v0.35 KCNJ2 Chirag Patel Tag disputed tag was added to gene: KCNJ2.
Motor Neurone Disease v1.39 EWSR1 Chirag Patel Tag disputed tag was added to gene: EWSR1.
Mendeliome v1.3594 EWSR1 Chirag Patel Tag disputed tag was added to gene: EWSR1.
Mendeliome v1.3594 UPK3A Chirag Patel commented on gene: UPK3A: ClinGen DISPUTED - Jan 2023
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.129 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from Congenital anomaly of kidney and urinary tract, MONDO:0019719 to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.129 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from Congenital anomaly of kidney and urinary tract, MONDO:0019719 to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.129 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from Congenital anomaly of kidney and urinary tract, MONDO:0019719 to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.129 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from Congenital anomaly of kidney and urinary tract, MONDO:0019719 to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Mendeliome v1.3594 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from CAKUT to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.128 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from Congenital anomaly of kidney and urinary tract, MONDO:0019719 to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.128 UPK3A Chirag Patel Phenotypes for gene: UPK3A were changed from to Congenital anomaly of kidney and urinary tract, MONDO:0019719
Mendeliome v1.3593 UPK3A Chirag Patel Tag disputed tag was added to gene: UPK3A.
Mendeliome v1.3593 Chirag Patel Added reviews for gene UPK3A from panel Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.127 UPK3A Chirag Patel Tag disputed tag was added to gene: UPK3A.
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.127 UPK3A Chirag Patel edited their review of gene: UPK3A: Added comment: ClinGen DISPUTED - Jan 2023; Changed phenotypes: Congenital anomaly of kidney and urinary tract, MONDO:0019719
Complement Deficiencies v1.2 THBD Chirag Patel Tag disputed tag was added to gene: THBD.
Complement Deficiencies v1.2 THBD Chirag Patel reviewed gene: THBD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3592 Chirag Patel Added reviews for gene ZFYVE27 from panel Hereditary Spastic Paraplegia - adult onset
Mendeliome v1.3591 ZFYVE27 Chirag Patel Tag disputed tag was added to gene: ZFYVE27.
Ataxia v1.63 PIK3R5 Chirag Patel commented on gene: PIK3R5: ClinGen DISPUTED - Apr 2025
Regression v0.595 PIK3R5 Chirag Patel Deleted their comment
Regression v0.595 Chirag Patel Added reviews for gene PIK3R5 from panel Cerebellar and Pontocerebellar Hypoplasia
Ataxia v1.62 PIK3R5 Chirag Patel Tag disputed tag was added to gene: PIK3R5.
Regression v0.594 PIK3R5 Chirag Patel Tag disputed tag was added to gene: PIK3R5.
Mendeliome v1.3590 PIK3R5 Chirag Patel Tag disputed tag was added to gene: PIK3R5.
Mendeliome v1.3591 Chirag Patel Added reviews for gene PIK3R5 from panel Cerebellar and Pontocerebellar Hypoplasia
Ataxia v1.63 Chirag Patel Added reviews for gene PIK3R5 from panel Cerebellar and Pontocerebellar Hypoplasia
Cerebellar and Pontocerebellar Hypoplasia v1.91 PIK3R5 Chirag Patel Tag disputed tag was added to gene: PIK3R5.
Cerebellar and Pontocerebellar Hypoplasia v1.91 PIK3R5 Chirag Patel commented on gene: PIK3R5: ClinGen DISPUTED - Apr 2025
Infertility and Recurrent Pregnancy Loss v1.52 CFAP47 Chirag Patel Marked gene: CFAP47 as ready
Infertility and Recurrent Pregnancy Loss v1.52 CFAP47 Chirag Patel Gene: cfap47 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.52 CFAP47 Chirag Patel Phenotypes for gene: CFAP47 were changed from Spermatogenic failure, X-linked, 3, MIM# 301059; Cystic kidney disease MONDO:0002473 to Spermatogenic failure, X-linked, 3, MIM# 301059
Infertility and Recurrent Pregnancy Loss v1.51 Chirag Patel Copied gene CFAP47 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.51 CFAP47 Chirag Patel gene: CFAP47 was added
gene: CFAP47 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CFAP47 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: CFAP47 were set to 33472045; 39698362
Phenotypes for gene: CFAP47 were set to Spermatogenic failure, X-linked, 3, MIM# 301059; Cystic kidney disease MONDO:0002473
Mendeliome v1.3590 CFAP47 Chirag Patel changed review comment from: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.

ClinGen DISPUTED - Feb 2025
Renal Macrocystic Disease v0.91 CFAP47 Chirag Patel commented on gene: CFAP47: ClinGen DISPUTED - Feb 2025
Renal Macrocystic Disease v0.91 CFAP47 Chirag Patel Tag disputed tag was added to gene: CFAP47.
Mitochondrial disease v0.1086 NUP62 Chirag Patel gene: NUP62 was added
gene: NUP62 was added to Mitochondrial disease. Sources: ClinGen
disputed tags were added to gene: NUP62.
Mode of inheritance for gene: NUP62 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUP62 were set to Leigh syndrome, MONDO:0009723
Review for gene: NUP62 was set to RED
Added comment: ClinGen DISPUTED - Dec 2020
Sources: ClinGen
Breast Cancer v1.18 MSH6 Chirag Patel Marked gene: MSH6 as ready
Breast Cancer v1.18 MSH6 Chirag Patel Gene: msh6 has been classified as Red List (Low Evidence).
Breast Cancer v1.18 PMS2 Chirag Patel Marked gene: PMS2 as ready
Breast Cancer v1.18 PMS2 Chirag Patel Gene: pms2 has been classified as Red List (Low Evidence).
Breast Cancer v1.18 RECQL Chirag Patel Marked gene: RECQL as ready
Breast Cancer v1.18 RECQL Chirag Patel Gene: recql has been classified as Red List (Low Evidence).
Breast Cancer v1.18 RECQL Chirag Patel gene: RECQL was added
gene: RECQL was added to Breast Cancer. Sources: ClinGen
disputed tags were added to gene: RECQL.
Mode of inheritance for gene: RECQL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RECQL were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: RECQL was set to RED
Added comment: ClinGen DISPUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.17 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Breast Cancer. Sources: ClinGen
disputed tags were added to gene: PMS2.
Mode of inheritance for gene: PMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PMS2 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: PMS2 was set to RED
Added comment: ClinGen DISPUTED - Dec 2023
Sources: ClinGen
Breast Cancer v1.16 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Breast Cancer. Sources: ClinGen
disputed tags were added to gene: MSH6.
Mode of inheritance for gene: MSH6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MSH6 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: MSH6 was set to RED
Added comment: ClinGen DISPUTED - Dec 2023
Sources: ClinGen
Colorectal Cancer and Polyposis v1.4 SEMA4A Chirag Patel Marked gene: SEMA4A as ready
Colorectal Cancer and Polyposis v1.4 SEMA4A Chirag Patel Gene: sema4a has been classified as Red List (Low Evidence).
Colorectal Cancer and Polyposis v1.4 SEMA4A Chirag Patel gene: SEMA4A was added
gene: SEMA4A was added to Colorectal Cancer and Polyposis. Sources: ClinGen
disputed tags were added to gene: SEMA4A.
Mode of inheritance for gene: SEMA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SEMA4A were set to Lynch syndrome, MONDO:0005835
Review for gene: SEMA4A was set to RED
Added comment: ClinGen DISPUTED - Mar 2024
Sources: ClinGen
Colorectal Cancer and Polyposis v1.3 MUTYH Chirag Patel edited their review of gene: MUTYH: Added comment: ClinGen DISPUTED (AD) - Mar 2023; Changed rating: RED; Changed phenotypes: Colorectal cancer, MONDO:0005575; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ovarian Cancer v1.6 BARD1 Chirag Patel Marked gene: BARD1 as ready
Ovarian Cancer v1.6 BARD1 Chirag Patel Gene: bard1 has been classified as Red List (Low Evidence).
Ovarian Cancer v1.6 BARD1 Chirag Patel gene: BARD1 was added
gene: BARD1 was added to Ovarian Cancer. Sources: ClinGen
disputed tags were added to gene: BARD1.
Mode of inheritance for gene: BARD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BARD1 were set to Familial ovarian cancer, MONDO:0016248
Review for gene: BARD1 was set to RED
Added comment: ClinGen DISPUTED - Aug 2024
Sources: ClinGen
Ovarian Cancer v1.5 MUTYH Chirag Patel Marked gene: MUTYH as ready
Ovarian Cancer v1.5 MUTYH Chirag Patel Gene: mutyh has been classified as Red List (Low Evidence).
Ovarian Cancer v1.5 MUTYH Chirag Patel gene: MUTYH was added
gene: MUTYH was added to Ovarian Cancer. Sources: ClinGen
disputed tags were added to gene: MUTYH.
Mode of inheritance for gene: MUTYH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MUTYH were set to Familial ovarian cancer, MONDO:0016248
Review for gene: MUTYH was set to RED
Added comment: ClinGen DISPUTED (AR and AD) - Dec 2023
Sources: ClinGen
Breast Cancer v1.15 MUTYH Chirag Patel Mode of inheritance for gene: MUTYH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Breast Cancer v1.14 MUTYH Chirag Patel Tag disputed tag was added to gene: MUTYH.
Breast Cancer v1.14 MUTYH Chirag Patel Deleted their comment
Breast Cancer v1.14 MUTYH Chirag Patel edited their review of gene: MUTYH: Added comment: ClinGen DISPUTED (AR) and REFUTED (AD) - Dec 2023; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3590 MYO1F Chirag Patel Marked gene: MYO1F as ready
Mendeliome v1.3590 MYO1F Chirag Patel Gene: myo1f has been classified as Red List (Low Evidence).
Mendeliome v1.3590 MYO1F Chirag Patel gene: MYO1F was added
gene: MYO1F was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: MYO1F.
Mode of inheritance for gene: MYO1F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1F were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1F was set to RED
Added comment: ClinGen DISPUTED - Oct 2024
Sources: ClinGen
Mendeliome v1.3589 CEMIP Chirag Patel Marked gene: CEMIP as ready
Mendeliome v1.3589 CEMIP Chirag Patel Gene: cemip has been classified as Red List (Low Evidence).
Mendeliome v1.3589 Chirag Patel Copied gene CEMIP from panel Deafness_IsolatedAndComplex
Mendeliome v1.3589 CEMIP Chirag Patel gene: CEMIP was added
gene: CEMIP was added to Mendeliome. Sources: Expert Review Red,ClinGen
disputed tags were added to gene: CEMIP.
Mode of inheritance for gene: CEMIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEMIP were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Deafness_IsolatedAndComplex v1.294 CEMIP Chirag Patel Marked gene: CEMIP as ready
Deafness_IsolatedAndComplex v1.294 CEMIP Chirag Patel Gene: cemip has been classified as Red List (Low Evidence).
Mendeliome v1.3588 MYO1C Chirag Patel Marked gene: MYO1C as ready
Mendeliome v1.3588 MYO1C Chirag Patel Gene: myo1c has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.294 GJA1 Chirag Patel Marked gene: GJA1 as ready
Deafness_IsolatedAndComplex v1.294 GJA1 Chirag Patel Gene: gja1 has been classified as Red List (Low Evidence).
Mendeliome v1.3588 Chirag Patel Copied gene MYO1C from panel Deafness_IsolatedAndComplex
Mendeliome v1.3588 MYO1C Chirag Patel gene: MYO1C was added
gene: MYO1C was added to Mendeliome. Sources: ClinGen
disputed tags were added to gene: MYO1C.
Mode of inheritance for gene: MYO1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1C were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Deafness_IsolatedAndComplex v1.294 MYO1C Chirag Patel Marked gene: MYO1C as ready
Deafness_IsolatedAndComplex v1.294 MYO1C Chirag Patel Gene: myo1c has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.294 MYO1F Chirag Patel gene: MYO1F was added
gene: MYO1F was added to Deafness_IsolatedAndComplex. Sources: ClinGen
disputed tags were added to gene: MYO1F.
Mode of inheritance for gene: MYO1F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1F were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1F was set to RED
Added comment: ClinGen DISPUTED - Oct 2024
Sources: ClinGen
Deafness_IsolatedAndComplex v1.293 MYO1F Chirag Patel gene: MYO1F was added
gene: MYO1F was added to Deafness_IsolatedAndComplex. Sources: ClinGen
disputed tags were added to gene: MYO1F.
Mode of inheritance for gene: MYO1F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1F were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1F was set to RED
Added comment: ClinGen DISPUTED - Oct 2024
Sources: ClinGen
Deafness_IsolatedAndComplex v1.293 MYO1C Chirag Patel gene: MYO1C was added
gene: MYO1C was added to Deafness_IsolatedAndComplex. Sources: ClinGen
disputed tags were added to gene: MYO1C.
Mode of inheritance for gene: MYO1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1C were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1C was set to RED
Added comment: ClinGen DISPUTED - Jun 2018
Sources: ClinGen
Deafness_IsolatedAndComplex v1.292 GJA1 Chirag Patel gene: GJA1 was added
gene: GJA1 was added to Deafness_IsolatedAndComplex. Sources: ClinGen
disputed tags were added to gene: GJA1.
Mode of inheritance for gene: GJA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GJA1 were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: GJA1 was set to RED
Added comment: ClinGen DISPUTED - Mar 2022
Sources: ClinGen
Deafness_IsolatedAndComplex v1.292 CEMIP Chirag Patel gene: CEMIP was added
gene: CEMIP was added to Deafness_IsolatedAndComplex. Sources: ClinGen
disputed tags were added to gene: CEMIP.
Mode of inheritance for gene: CEMIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEMIP were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: CEMIP was set to RED
Added comment: ClinGen DISPUTED - Jul 2018
Sources: ClinGen
Deafness_IsolatedAndComplex v1.291 GJB3 Chirag Patel Tag disputed tag was added to gene: GJB3.
Clefting disorders v0.281 SIX5 Chirag Patel Tag disputed tag was added to gene: SIX5.
Deafness_IsolatedAndComplex v1.291 TMTC2 Chirag Patel Tag disputed tag was added to gene: TMTC2.
Mendeliome v1.3587 PDLIM3 Chirag Patel Tag disputed tag was added to gene: PDLIM3.
Mendeliome v1.3587 PDLIM3 Chirag Patel Phenotypes for gene: PDLIM3 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy; Dilated cardiomyopathy, MONDO:0005021
Dilated Cardiomyopathy v1.51 MYL3 Chirag Patel Marked gene: MYL3 as ready
Dilated Cardiomyopathy v1.51 MYL3 Chirag Patel Gene: myl3 has been classified as Red List (Low Evidence).
Mendeliome v1.3586 Chirag Patel Added reviews for gene PDLIM3 from panel Dilated Cardiomyopathy
Dilated Cardiomyopathy v1.51 PSEN1 Chirag Patel Marked gene: PSEN1 as ready
Dilated Cardiomyopathy v1.51 PSEN1 Chirag Patel Gene: psen1 has been classified as Red List (Low Evidence).
Mendeliome v1.3585 Chirag Patel Copied gene PKP2 from panel Dilated Cardiomyopathy
Mendeliome v1.3585 PKP2 Chirag Patel gene: PKP2 was added
gene: PKP2 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to 15489853; 16567567; 30562116; 35059364; 38050058
Phenotypes for gene: PKP2 were set to Arrhythmogenic right ventricular dysplasia 9 (MIM#609040); Dilated cardiomyopathy, MONDO:0005021, PKP2-related; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Dilated Cardiomyopathy v1.51 PKP2 Chirag Patel reviewed gene: PKP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v1.51 PSEN1 Chirag Patel gene: PSEN1 was added
gene: PSEN1 was added to Dilated Cardiomyopathy. Sources: ClinGen
disputed tags were added to gene: PSEN1.
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PSEN1 were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: PSEN1 was set to RED
Added comment: ClinGen DISPUTED - May 2025
Sources: ClinGen
Dilated Cardiomyopathy v1.51 MYL3 Chirag Patel gene: MYL3 was added
gene: MYL3 was added to Dilated Cardiomyopathy. Sources: ClinGen
disputed tags were added to gene: MYL3.
Mode of inheritance for gene: MYL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYL3 were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: MYL3 was set to RED
Added comment: ClinGen DISPUTED - May 2025
Sources: ClinGen
Dilated Cardiomyopathy v1.50 PDLIM3 Chirag Patel Marked gene: PDLIM3 as ready
Dilated Cardiomyopathy v1.50 PDLIM3 Chirag Patel Gene: pdlim3 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v1.50 PDLIM3 Chirag Patel gene: PDLIM3 was added
gene: PDLIM3 was added to Dilated Cardiomyopathy. Sources: ClinGen
disputed tags were added to gene: PDLIM3.
Mode of inheritance for gene: PDLIM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDLIM3 were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: PDLIM3 was set to RED
Added comment: ClinGen DISPUTED - May 2025
Sources: ClinGen
Mendeliome v1.3584 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Genetic Epilepsy v1.277 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Callosome v0.569 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Regression v0.594 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Intellectual disability syndromic and non-syndromic v1.429 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Ataxia v1.62 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Progressive Myoclonic Epilepsy v0.22 PRICKLE1 Chirag Patel Tag disputed tag was added to gene: PRICKLE1.
Mendeliome v1.3584 CPA6 Chirag Patel Source Victorian Clinical Genetics Services was removed from CPA6.
Source ClinGen was added to CPA6.
Mode of inheritance for gene CPA6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.277 CPA6 Chirag Patel Source Victorian Clinical Genetics Services was removed from CPA6.
Source Australian Genomics Health Alliance Epilepsy Flagship was removed from CPA6.
Source ClinGen was added to CPA6.
Mode of inheritance for gene CPA6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.276 CASR Chirag Patel Marked gene: CASR as ready
Genetic Epilepsy v1.276 CASR Chirag Patel Gene: casr has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.276 CASR Chirag Patel gene: CASR was added
gene: CASR was added to Genetic Epilepsy. Sources: ClinGen
disputed tags were added to gene: CASR.
Mode of inheritance for gene: CASR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CASR were set to Epilepsy, MONDO:0005027
Review for gene: CASR was set to RED
Added comment: ClinGen DISPUTED - Mar 2021
Sources: ClinGen
Mendeliome v1.3583 FAAP24 Chirag Patel Tag disputed tag was added to gene: FAAP24.
Mendeliome v1.3583 FAAP24 Chirag Patel reviewed gene: FAAP24: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Disorders of immune dysregulation v1.34 FAAP24 Chirag Patel Tag disputed tag was added to gene: FAAP24.
Mendeliome v1.3583 LIMS2 Chirag Patel Tag disputed tag was added to gene: LIMS2.
Mendeliome v1.3583 Chirag Patel Added reviews for gene LIMS2 from panel Myopathy - paediatric onset
Interstitial Lung Disease v1.3 BMPR1B Chirag Patel Classified gene: BMPR1B as Red List (low evidence)
Interstitial Lung Disease v1.3 BMPR1B Chirag Patel Gene: bmpr1b has been classified as Red List (Low Evidence).
Interstitial Lung Disease v1.2 BMPR1B Chirag Patel Tag disputed tag was added to gene: BMPR1B.
Interstitial Lung Disease v1.2 BMPR1B Chirag Patel reviewed gene: BMPR1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.46 BMPR1A Chirag Patel Marked gene: BMPR1A as ready
Pulmonary Arterial Hypertension v1.46 BMPR1A Chirag Patel Gene: bmpr1a has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.46 BMPR1A Chirag Patel gene: BMPR1A was added
gene: BMPR1A was added to Pulmonary Arterial Hypertension. Sources: ClinGen
disputed tags were added to gene: BMPR1A.
Mode of inheritance for gene: BMPR1A was set to Unknown
Phenotypes for gene: BMPR1A were set to Pulmonary arterial hypertension MONDO:0015924
Review for gene: BMPR1A was set to RED
Added comment: ClinGen DISPUTED - Oct 2022
Sources: ClinGen
Rasopathy v0.111 RASA1 Chirag Patel Marked gene: RASA1 as ready
Rasopathy v0.111 RASA1 Chirag Patel Gene: rasa1 has been classified as Red List (Low Evidence).
Rasopathy v0.111 RASA1 Chirag Patel gene: RASA1 was added
gene: RASA1 was added to Rasopathy. Sources: ClinGen
disputed tags were added to gene: RASA1.
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RASA1 were set to Noonan syndrome, MONDO:0018997
Review for gene: RASA1 was set to RED
Added comment: ClinGen DISPUTED - Jun 2018
Sources: ClinGen
Rasopathy v0.110 NSUN2 Chirag Patel Marked gene: NSUN2 as ready
Rasopathy v0.110 NSUN2 Chirag Patel Gene: nsun2 has been classified as Red List (Low Evidence).
Rasopathy v0.110 NSUN2 Chirag Patel gene: NSUN2 was added
gene: NSUN2 was added to Rasopathy. Sources: ClinGen
disputed tags were added to gene: NSUN2.
Mode of inheritance for gene: NSUN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NSUN2 were set to RASopathy, MONDO:0021060
Review for gene: NSUN2 was set to RED
Added comment: ClinGen DISPUTED - Feb 2019
Sources: ClinGen
Rasopathy v0.109 KAT6B Chirag Patel Marked gene: KAT6B as ready
Rasopathy v0.109 KAT6B Chirag Patel Gene: kat6b has been classified as Red List (Low Evidence).
Rasopathy v0.109 KAT6B Chirag Patel gene: KAT6B was added
gene: KAT6B was added to Rasopathy. Sources: ClinGen
disputed tags were added to gene: KAT6B.
Mode of inheritance for gene: KAT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KAT6B were set to RASopathy, MONDO:0021060
Review for gene: KAT6B was set to RED
Added comment: ClinGen DISPUTED - Feb 2019
Sources: ClinGen
Colorectal Cancer and Polyposis v1.3 PMS1 Chirag Patel Marked gene: PMS1 as ready
Colorectal Cancer and Polyposis v1.3 PMS1 Chirag Patel Gene: pms1 has been classified as Red List (Low Evidence).
Colorectal Cancer and Polyposis v1.3 PMS1 Chirag Patel gene: PMS1 was added
gene: PMS1 was added to Colorectal Cancer and Polyposis. Sources: ClinGen
refuted tags were added to gene: PMS1.
Mode of inheritance for gene: PMS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PMS1 were set to Lynch syndrome, MONDO:0005835
Review for gene: PMS1 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Ovarian Cancer v1.4 RAD50 Chirag Patel Marked gene: RAD50 as ready
Ovarian Cancer v1.4 RAD50 Chirag Patel Gene: rad50 has been classified as Red List (Low Evidence).
Ovarian Cancer v1.4 RAD50 Chirag Patel gene: RAD50 was added
gene: RAD50 was added to Ovarian Cancer. Sources: ClinGen
refuted tags were added to gene: RAD50.
Mode of inheritance for gene: RAD50 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD50 were set to Familial ovarian cancer, MONDO:0016248
Review for gene: RAD50 was set to RED
Added comment: ClinGen REFUTED - Feb 2024
Sources: ClinGen
Early-onset Dementia v1.52 SQSTM1 Krithika Murali Classified gene: SQSTM1 as Amber List (moderate evidence)
Early-onset Dementia v1.52 SQSTM1 Krithika Murali Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Breast Cancer v1.14 XRCC2 Chirag Patel Marked gene: XRCC2 as ready
Breast Cancer v1.14 XRCC2 Chirag Patel Gene: xrcc2 has been classified as Red List (Low Evidence).
Breast Cancer v1.14 SLX4 Chirag Patel Marked gene: SLX4 as ready
Breast Cancer v1.14 SLX4 Chirag Patel Gene: slx4 has been classified as Red List (Low Evidence).
Breast Cancer v1.14 RINT1 Chirag Patel Marked gene: RINT1 as ready
Breast Cancer v1.14 RINT1 Chirag Patel Gene: rint1 has been classified as Red List (Low Evidence).
Breast Cancer v1.14 RAD50 Chirag Patel Marked gene: RAD50 as ready
Breast Cancer v1.14 RAD50 Chirag Patel Gene: rad50 has been classified as Red List (Low Evidence).
Breast Cancer v1.14 PIK3CA Chirag Patel Marked gene: PIK3CA as ready
Breast Cancer v1.14 PIK3CA Chirag Patel Gene: pik3ca has been classified as Red List (Low Evidence).
Breast Cancer v1.14 XRCC2 Chirag Patel gene: XRCC2 was added
gene: XRCC2 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: XRCC2.
Mode of inheritance for gene: XRCC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: XRCC2 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: XRCC2 was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.13 SLX4 Chirag Patel gene: SLX4 was added
gene: SLX4 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: SLX4.
Mode of inheritance for gene: SLX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLX4 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: SLX4 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Breast Cancer v1.12 RINT1 Chirag Patel gene: RINT1 was added
gene: RINT1 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: RINT1.
Mode of inheritance for gene: RINT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RINT1 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: RINT1 was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.11 RAD50 Chirag Patel gene: RAD50 was added
gene: RAD50 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: RAD50.
Mode of inheritance for gene: RAD50 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD50 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: RAD50 was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.10 PIK3CA Chirag Patel gene: PIK3CA was added
gene: PIK3CA was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: PIK3CA.
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3CA were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: PIK3CA was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Early-onset Dementia v1.51 SQSTM1 Krithika Murali Classified gene: SQSTM1 as Amber List (moderate evidence)
Early-onset Dementia v1.51 SQSTM1 Krithika Murali Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.51 SQSTM1 Krithika Murali Classified gene: SQSTM1 as Amber List (moderate evidence)
Early-onset Dementia v1.51 SQSTM1 Krithika Murali Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v1.50 SQSTM1 Krithika Murali commented on gene: SQSTM1
Dilated Cardiomyopathy v1.49 TMPO Chirag Patel Marked gene: TMPO as ready
Dilated Cardiomyopathy v1.49 TMPO Chirag Patel Gene: tmpo has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v1.49 TMPO Chirag Patel gene: TMPO was added
gene: TMPO was added to Dilated Cardiomyopathy. Sources: ClinGen
refuted tags were added to gene: TMPO.
Mode of inheritance for gene: TMPO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TMPO were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: TMPO was set to RED
Added comment: ClinGen REFUTED - Nov 2016
Sources: ClinGen
Cardiomyopathy_Paediatric v0.207 TMPO Chirag Patel Tag refuted tag was added to gene: TMPO.
Cardiomyopathy_Paediatric v0.207 TMPO Chirag Patel reviewed gene: TMPO: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3582 TMPO Chirag Patel Tag refuted tag was added to gene: TMPO.
Genetic Epilepsy v1.275 SRPX2 Chirag Patel Marked gene: SRPX2 as ready
Genetic Epilepsy v1.275 SRPX2 Chirag Patel Gene: srpx2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.275 SRPX2 Chirag Patel gene: SRPX2 was added
gene: SRPX2 was added to Genetic Epilepsy. Sources: ClinGen
refuted tags were added to gene: SRPX2.
Mode of inheritance for gene: SRPX2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SRPX2 were set to Epilepsy, MONDO:0005027
Review for gene: SRPX2 was set to RED
Added comment: ClinGen REFUTED - Oct 2023
Sources: ClinGen
Polymicrogyria and Schizencephaly v0.201 SRPX2 Chirag Patel Tag refuted tag was added to gene: SRPX2.
Polymicrogyria and Schizencephaly v0.201 SRPX2 Chirag Patel reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3582 SRPX2 Chirag Patel reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3582 SRPX2 Chirag Patel Tag refuted tag was added to gene: SRPX2.
Intellectual disability syndromic and non-syndromic v1.429 SRPX2 Chirag Patel Tag refuted tag was added to gene: SRPX2.
Intellectual disability syndromic and non-syndromic v1.429 SRPX2 Chirag Patel reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v1.274 SCN9A Chirag Patel Tag refuted tag was added to gene: SCN9A.
Mendeliome v1.3582 Chirag Patel Copied gene RANGRF from panel Brugada syndrome
Mendeliome v1.3582 RANGRF Chirag Patel gene: RANGRF was added
gene: RANGRF was added to Mendeliome. Sources: Expert Review Red,ClinGen
refuted tags were added to gene: RANGRF.
Mode of inheritance for gene: RANGRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RANGRF were set to Brugada syndrome, MONDO:0015263
Brugada syndrome v0.35 RANGRF Chirag Patel Marked gene: RANGRF as ready
Brugada syndrome v0.35 RANGRF Chirag Patel Gene: rangrf has been classified as Red List (Low Evidence).
Brugada syndrome v0.35 RANGRF Chirag Patel gene: RANGRF was added
gene: RANGRF was added to Brugada syndrome. Sources: ClinGen
refuted tags were added to gene: RANGRF.
Mode of inheritance for gene: RANGRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RANGRF were set to Brugada syndrome, MONDO:0015263
Review for gene: RANGRF was set to RED
Added comment: ClinGen REFUTED - Oct 2025
Sources: ClinGen
Mendeliome v1.3581 Chirag Patel Copied gene RAB40AL from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3581 RAB40AL Chirag Patel gene: RAB40AL was added
gene: RAB40AL was added to Mendeliome. Sources: Expert Review Red,Genetic Health Queensland
refuted tags were added to gene: RAB40AL.
Mode of inheritance for gene: RAB40AL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB40AL were set to 25044830
Phenotypes for gene: RAB40AL were set to MENTAL RETARDATION, X-LINKED, SYNDROMIC, MARTIN-PROBST TYPE
Intellectual disability syndromic and non-syndromic v1.429 RAB40AL Chirag Patel Tag refuted tag was added to gene: RAB40AL.
Ovarian Cancer v1.3 MRE11 Chirag Patel Marked gene: MRE11 as ready
Ovarian Cancer v1.3 MRE11 Chirag Patel Gene: mre11 has been classified as Red List (Low Evidence).
Ovarian Cancer v1.3 MRE11 Chirag Patel gene: MRE11 was added
gene: MRE11 was added to Ovarian Cancer. Sources: ClinGen
refuted tags were added to gene: MRE11.
Mode of inheritance for gene: MRE11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MRE11 were set to Familial ovarian cancer, MONDO:0016248
Review for gene: MRE11 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Breast Cancer v1.9 NBN Chirag Patel Marked gene: NBN as ready
Breast Cancer v1.9 NBN Chirag Patel Gene: nbn has been classified as Red List (Low Evidence).
Breast Cancer v1.9 NBN Chirag Patel gene: NBN was added
gene: NBN was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: NBN.
Mode of inheritance for gene: NBN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NBN were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: NBN was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.8 MUTYH Chirag Patel Marked gene: MUTYH as ready
Breast Cancer v1.8 MUTYH Chirag Patel Gene: mutyh has been classified as Red List (Low Evidence).
Breast Cancer v1.8 MUTYH Chirag Patel gene: MUTYH was added
gene: MUTYH was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: MUTYH.
Mode of inheritance for gene: MUTYH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MUTYH were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: MUTYH was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Breast Cancer v1.7 MSH2 Chirag Patel Marked gene: MSH2 as ready
Breast Cancer v1.7 MSH2 Chirag Patel Gene: msh2 has been classified as Red List (Low Evidence).
Breast Cancer v1.7 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: MSH2.
Mode of inheritance for gene: MSH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MSH2 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: MSH2 was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.6 MRE11 Chirag Patel Marked gene: MRE11 as ready
Breast Cancer v1.6 MRE11 Chirag Patel Gene: mre11 has been classified as Red List (Low Evidence).
Breast Cancer v1.6 MRE11 Chirag Patel gene: MRE11 was added
gene: MRE11 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: MRE11.
Mode of inheritance for gene: MRE11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MRE11 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: MRE11 was set to RED
Added comment: ClinGen REFUTED - Mar 2023
Sources: ClinGen
Breast Cancer v1.5 MLH1 Chirag Patel Marked gene: MLH1 as ready
Breast Cancer v1.5 MLH1 Chirag Patel Gene: mlh1 has been classified as Red List (Low Evidence).
Breast Cancer v1.5 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: MLH1.
Mode of inheritance for gene: MLH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MLH1 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: MLH1 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Deafness_IsolatedAndComplex v1.291 MYO1A Chirag Patel Marked gene: MYO1A as ready
Deafness_IsolatedAndComplex v1.291 MYO1A Chirag Patel Gene: myo1a has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.291 MYO1A Chirag Patel gene: MYO1A was added
gene: MYO1A was added to Deafness_IsolatedAndComplex. Sources: ClinGen
refuted tags were added to gene: MYO1A.
Mode of inheritance for gene: MYO1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MYO1A were set to Nonsyndromic genetic hearing loss, MONDO:0019497
Review for gene: MYO1A was set to RED
Added comment: ClinGen REFUTED - Jan 2018
Sources: ClinGen
Mendeliome v1.3580 MYO1A Chirag Patel Classified gene: MYO1A as Red List (low evidence)
Mendeliome v1.3580 MYO1A Chirag Patel Gene: myo1a has been classified as Red List (Low Evidence).
Congenital Diarrhoea v1.30 MYO1A Chirag Patel Classified gene: MYO1A as Red List (low evidence)
Congenital Diarrhoea v1.30 MYO1A Chirag Patel Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v1.3579 MYO1A Chirag Patel reviewed gene: MYO1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital diarrhea, MONDO:0000824; Mode of inheritance: None
Congenital Diarrhoea v1.30 MYO1A Chirag Patel Classified gene: MYO1A as Red List (low evidence)
Congenital Diarrhoea v1.30 MYO1A Chirag Patel Gene: myo1a has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.274 MAGI2 Chirag Patel reviewed gene: MAGI2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v1.274 MAGI2 Chirag Patel Deleted their review
Genetic Epilepsy v1.274 MAGI2 Chirag Patel commented on gene: MAGI2
Genetic Epilepsy v1.274 MAGI2 Chirag Patel Tag refuted tag was added to gene: MAGI2.
Monogenic Diabetes v0.152 KLF11 Chirag Patel Tag refuted tag was added to gene: KLF11.
Maturity-onset Diabetes of the Young v1.24 KLF11 Chirag Patel Tag refuted tag was added to gene: KLF11.
Mendeliome v1.3579 KLF11 Chirag Patel Tag refuted tag was added to gene: KLF11.
Syndromic Retinopathy v0.234 HARS Chirag Patel Tag refuted tag was added to gene: HARS.
Usher Syndrome v1.5 HARS Chirag Patel Tag refuted tag was added to gene: HARS.
Deafness_IsolatedAndComplex v1.290 HARS Chirag Patel Tag refuted tag was added to gene: HARS.
Breast Cancer v1.4 EPCAM Chirag Patel Marked gene: EPCAM as ready
Breast Cancer v1.4 EPCAM Chirag Patel Gene: epcam has been classified as Red List (Low Evidence).
Breast Cancer v1.4 GEN1 Chirag Patel Marked gene: GEN1 as ready
Breast Cancer v1.4 GEN1 Chirag Patel Gene: gen1 has been classified as Red List (Low Evidence).
Mendeliome v1.3579 GEN1 Chirag Patel Marked gene: GEN1 as ready
Mendeliome v1.3579 GEN1 Chirag Patel Gene: gen1 has been classified as Red List (Low Evidence).
Mendeliome v1.3579 Chirag Patel Copied gene GEN1 from panel Breast Cancer
Mendeliome v1.3579 GEN1 Chirag Patel gene: GEN1 was added
gene: GEN1 was added to Mendeliome. Sources: ClinGen
refuted tags were added to gene: GEN1.
Mode of inheritance for gene: GEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GEN1 were set to Hereditary breast carcinoma, MONDO:0016419
Breast Cancer v1.4 GEN1 Chirag Patel gene: GEN1 was added
gene: GEN1 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: GEN1.
Mode of inheritance for gene: GEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GEN1 were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: GEN1 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Fetal anomalies v1.470 FANCM Chirag Patel Tag refuted tag was added to gene: FANCM.
Growth failure v1.83 FANCM Chirag Patel Tag refuted tag was added to gene: FANCM.
Colorectal Cancer and Polyposis v1.2 EXO1 Chirag Patel gene: EXO1 was added
gene: EXO1 was added to Colorectal Cancer and Polyposis. Sources: ClinGen
refuted tags were added to gene: EXO1.
Mode of inheritance for gene: EXO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EXO1 were set to Lynch syndrome, MONDO:0005835
Review for gene: EXO1 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Breast Cancer v1.3 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: EPCAM.
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Hereditary breast carcinoma, MONDO:0016419
Review for gene: EPCAM was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Mendeliome v1.3578 EFHC1 Chirag Patel commented on gene: EFHC1
Mendeliome v1.3578 EFHC1 Chirag Patel Tag disputed was removed from gene: EFHC1.
Tag refuted tag was added to gene: EFHC1.
Ovarian Cancer v1.2 CHEK2 Chirag Patel gene: CHEK2 was added
gene: CHEK2 was added to Ovarian Cancer. Sources: ClinGen
refuted tags were added to gene: CHEK2.
Mode of inheritance for gene: CHEK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHEK2 were set to Familial ovarian cancer, MONDO:0016248
Review for gene: CHEK2 was set to RED
Added comment: ClinGen REFUTED - Apr 2024
Sources: ClinGen
Breast Cancer v1.2 BRIP1 Chirag Patel Marked gene: BRIP1 as ready
Breast Cancer v1.2 BRIP1 Chirag Patel Gene: brip1 has been classified as Red List (Low Evidence).
Breast Cancer v1.2 BRIP1 Chirag Patel gene: BRIP1 was added
gene: BRIP1 was added to Breast Cancer. Sources: ClinGen
refuted tags were added to gene: BRIP1.
Mode of inheritance for gene: BRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRIP1 were set to Hereditary breast carcinoma MONDO:0016419
Review for gene: BRIP1 was set to RED
Added comment: ClinGen REFUTED - Dec 2023
Sources: ClinGen
Genetic Epilepsy v1.274 CHRNA7 Chirag Patel Tag refuted tag was added to gene: CHRNA7.
Mendeliome v1.3578 CHRNA7 Chirag Patel Tag refuted tag was added to gene: CHRNA7.
Intellectual disability syndromic and non-syndromic v1.429 CPA6 Chirag Patel Tag refuted tag was added to gene: CPA6.
Motor Neurone Disease v1.39 DAO Chirag Patel Tag refuted tag was added to gene: DAO.
Mendeliome v1.3578 CRH Chirag Patel Marked gene: CRH as ready
Mendeliome v1.3578 CRH Chirag Patel Gene: crh has been classified as Red List (Low Evidence).
Mendeliome v1.3578 Chirag Patel Copied gene CRH from panel Genetic Epilepsy
Mendeliome v1.3578 CRH Chirag Patel gene: CRH was added
gene: CRH was added to Mendeliome. Sources: Expert Review Red,ClinGen
refuted tags were added to gene: CRH.
Mode of inheritance for gene: CRH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRH were set to Epilepsy, MONDO:0005027
Genetic Epilepsy v1.274 CRH Chirag Patel Marked gene: CRH as ready
Genetic Epilepsy v1.274 CRH Chirag Patel Gene: crh has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.274 CRH Chirag Patel gene: CRH was added
gene: CRH was added to Genetic Epilepsy. Sources: ClinGen
refuted tags were added to gene: CRH.
Mode of inheritance for gene: CRH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRH were set to Epilepsy, MONDO:0005027
Review for gene: CRH was set to RED
Added comment: ClinGen REFUTED - Sep 2021
Sources: ClinGen
Monogenic Diabetes v0.152 BLK Chirag Patel Tag refuted tag was added to gene: BLK.
Intellectual disability syndromic and non-syndromic v1.429 ADRA2B Chirag Patel Tag refuted tag was added to gene: ADRA2B.
Mendeliome v1.3577 ADRA2B Chirag Patel Tag refuted tag was added to gene: ADRA2B.
Genetic Epilepsy v1.273 ADRA2B Chirag Patel Tag refuted tag was added to gene: ADRA2B.
Mendeliome v1.3577 EXOSC10 Rylee Peters changed review comment from: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in panelapp), and encompass many genes.
Sources: Literature; to: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in Panelapp), and encompass many genes.
Sources: Literature
Mendeliome v1.3577 EXOSC10 Rylee Peters gene: EXOSC10 was added
gene: EXOSC10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOSC10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EXOSC10 were set to 41132091
Phenotypes for gene: EXOSC10 were set to Microcephaly, MONDO:0001149, EXOSC10-related
Review for gene: EXOSC10 was set to AMBER
Added comment: PMID: 41132091 | Article describes four unrelated individuals with heterozygous de novo EXOSC10 variants (1x missense and 4x microdeletions within the 1p36 region) presenting with primary microcephaly, anomalies of cortical structures, intellectual disability and global developmental delay. Exosc10 heterozygous knockout mice exhibited reduced cortical size resembling microcephaly, with a more severe phenotype observed in homozygous knockout mice.

However, these microdeletions occur within the 1p36 region, which is associated with chromosome 1p36 deletion syndrome (green in panelapp), and encompass many genes.
Sources: Literature
Renal Macrocystic Disease v0.91 UMOD Noor Al-Ali reviewed gene: UMOD: Rating: GREEN; Mode of pathogenicity: Other; Publications: (PMID: 23988501, 12471200, 32954071, 33397327, 23396133, 32450155); Phenotypes: Onset at adolescent or adult age, arterial hypertension (in some patients), renal insufficiency, nephropathy, renal failure, polydipsia, polyuria, impaired urinary concentration, chronic interstitial nephritis, tubulointerstitial abnormalities, tubular atrophy, interstitial fibrosis, hyaline material deposited around tubules, thickening of the basement membrane, medullary cysts (in some patients), glomerulosclerosis (in some patients), glomerulocystic kidney disease (in some patients), dilatation of Bowman’s space in glomeruli, rudimentary glomerular tufts, gout, hyperuricemia, decreased urinary excretion of uromodulin, onset of hyperuricemia or gout in young adulthood, slowly progressive disorder.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 UMOD Noor Al-Ali Deleted their review
Renal Macrocystic Disease v0.91 MUC1 Noor Al-Ali reviewed gene: MUC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: (PMID: 23396133, 29967284, 29156055); Phenotypes: Hypertension, impaired renal function, impaired renal creatinine clearance, impaired renal uric acid clearance, salt wasting, small kidneys, tubulointerstitial nephritis, tubulointerstitial fibrosis, interstitial inflammation, glomerulosclerosis, medullary cysts, corticomedullary cysts, tubular atrophy, cortical atrophy, disintegration of the tubular basement membrane, end-stage renal failure, gout, anemia, hyperuricemia, increased serum creatinine, decreased glomerular filtration rate (GFR), adult onset (range 34 to 66 years).; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 MUC1 Noor Al-Ali Deleted their review
Renal Macrocystic Disease v0.91 HNF1B Noor Al-Ali reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 39114399, 38044981, 29576871, 33305128, 25700310, 22432796); Phenotypes: Congenital anomalies of the kidney and urinary tract (CAKUT), chronic renal failure, structural kidney abnormalities, unilateral kidney agenesis, renal cysts, renal hypoplasia, renal parenchymal disease, interstitial fibrosis, cortical atrophy, abnormal nephrogenesis, decreased numbers of glomeruli, enlarged glomeruli, glomerular tufts, glomerular cysts, oligomeganephronia, abnormal renal calyces, abnormal renal pelvises, pelviureteric junction obstruction, hypoplastic glomerulocystic kidney disease, reduced fractional excretion of uric acid, renal calculi, diabetes mellitus, impaired glucose tolerance, glucosuria, proteinuria, increased serum creatinine, hyperuricemia.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 HNF1B Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 EPM2A Noor Al-Ali reviewed gene: EPM2A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 40442642, 35257260, 27574708, 40442642, 36211619, and many more); Phenotypes: Progressive loss of vision, photosensitivity, hepatic failure (not common), progressive myoclonic epilepsy, generalized tonic-clonic seizures, absence seizures, simple partial occipital seizures, simple partial seizures with secondary generalization, myoclonus, ataxia, progressive dementia, neurological deterioration, loss of ambulation, intracellular PAS-positive polyglucosan inclusion bodies (“Lafora bodies”), intracellular PAS-positive polyglucosan inclusion bodies (“Lafora bodies”) can be found in various tissues (brain, liver, muscle, heart, skin).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CTSF Noor Al-Ali reviewed gene: CTSF: Rating: RED; 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: No publications showing an association between pathogenic variants of the CTSF gene and progressive myoclonic epilepsy (PME); Phenotypes: : Progressive cognitive decline, dementia, motor abnormalities, tremor, ataxia, dysarthria, cerebellar signs, extrapyramidal signs, myoclonus, perioral dyskinesias, hyperreflexia, extensor plantar responses, primitive reflexes, seizures, diffuse cerebral atrophy, cerebellar atrophy, accumulation of autofluorescent material in neurons, behavioral changes, emotional lability, depression, skin fibroblasts showing osmiophilic cytoplasmic inclusions.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CTSD Noor Al-Ali reviewed gene: CTSD: Rating: RED; 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: No publications showing an association between this gene and progressive myoclonic epilepsy (PME); Phenotypes: Microcephaly, sloping forehead, low-set ears, progressive loss of vision, retinitis pigmentosa, retinal atrophy, broad nasal bridge, apnea, respiratory failure, overriding sutures, obliterated fontanelles, intracellular granular osmiophilic deposits, spasticity, rigidity, seizures, status epilepticus, ataxia, some patients may show normal early development, cognitive decline, severe intellectual disability, loss of motor functions, MRI shows cerebral atrophy, MRI shows cerebellar atrophy, neuronal loss in the cerebrum and cerebellum, glial activation, white matter lacks axons and myelin, autofluorescent lipopigment in neurons, granular osmiophilic cytoplasmic deposits in Schwann cells, myelin-like lamellar structures in Schwann cells.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CLN8 Noor Al-Ali reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 30741402, 26443629, 29422019, 17129765); Phenotypes: Progressive vision loss, developmental regression, seizures, ataxia, speech and language difficulties, myoclonus, EEG abnormalities, cerebral atrophy, cerebellar atrophy, autofluorescent lipopigment in neurons, intracellular fingerprint profiles on ultrastructural analysis, intracellular curvilinear profiles on ultrastructural analysis, onset at 2 to 7 years of age, most patients lose ambulation two years after onset.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CLN6 Noor Al-Ali reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 21549341, 30561534, 33024953, 34597687); Phenotypes: Seizures, cerebellar ataxia, extrapyramidal signs, myoclonus, dementia, cerebral atrophy, autofluorescent lipopigment in neurons, leukoencephalopathy on CT and MRI, behavioral changes, depression, auditory and visual hallucinations, granular osmiophilic deposits (GROD) in cells resulting in “fingerprint” profiles ultrastructurally, granular osmiophilic deposits (GROD) in cells resulting in “curvilinear” profiles ultrastructurally, granular osmiophilic deposits (GROD) in cells resulting in “rectilinear” profiles ultrastructurally, onset in adulthood (third to fourth decade).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CLN5 Noor Al-Ali reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 20157158, 41003830, 39667065, 22532218, 32983231); Phenotypes: Onset at 4 to 7 years, progressive vision loss, retinal degeneration, nystagmus, clumsiness, motor deterioration, developmental regression, ataxia, dysarthria, dysmetria, dysdiadochokinesis, seizures, myoclonus, intellectual disability, cognitive impairment, neurophysiologic abnormalities (EEG, VEP, SEP), characteristic findings on MRI, autofluorescent lipopigment in neurons, cerebellar atrophy (in one family), concentration difficulties, “fingerprint” profiles ultrastructurally, “curvilinear” profiles ultrastructurally, “rectilinear” profiles ultrastructurally.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CLN3 Noor Al-Ali reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 9311735, 24827497, 21990111, 31568712, 30884409); Phenotypes: Onset at 4 to 10 years, progressive vision loss (4 to 10 years), blindness (6 to 14 years), retinitis pigmentosa, macular degeneration, optic atrophy, abolished electroretinogram (ERG), glaucoma, lens-induced, cataract, juvenile-onset mature, concentric hypertrophic cardiomyopathy, severe (later onset in protracted cases), autophagic vacuoles seen on biopsy (in some patients), intermyofibrillar and subsarcolemmal accumulation of electron-dense material (in some patients), psychomotor degeneration, intellectual disability, dementia, extrapyramidal signs, myoclonus, parkinsonism, cerebellar signs, progressive inability to walk, seizures, dysarthria, autofluorescent lipopigment in neurons, cerebral atrophy, difficulty in school, behavioural changes, mood disturbances, anxiety, psychosis, vacuolated lymphocytes, lipopigment in extraneuronal cells, “fingerprint profiles” ultrastructurally in cells, “curvilinear profiles” ultrastructurally in cells.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Progressive Myoclonic Epilepsy v0.22 CLN8 Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 CLN6 Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 CLN5 Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 CLN3 Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 CTSD Noor Al-Ali Deleted their review
Progressive Myoclonic Epilepsy v0.22 CTSD Noor Al-Ali reviewed gene: CTSD: Rating: RED; 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: No publication showing an association between this gene and progressive myoclonic epilepsy (PME); Phenotypes: Microcephaly, sloping forehead, low-set ears, progressive loss of vision, retinitis pigmentosa, retinal atrophy, broad nasal bridge, apnea, respiratory failure, overriding sutures, obliterated fontanelles, intracellular granular osmiophilic deposits, spasticity, rigidity, seizures, status epilepticus, ataxia, some patients may show normal early development, cognitive decline, severe intellectual disability, loss of motor functions, MRI shows cerebral atrophy, MRI shows cerebellar atrophy, neuronal loss in the cerebrum and cerebellum, glial activation, white matter lacks axons and myelin, autofluorescent lipopigment in neurons, granular osmiophilic cytoplasmic deposits in Schwann cells, myelin-like lamellar structures in Schwann cells.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Myoclonic Epilepsy v0.22 CLN8 Noor Al-Ali reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 30741402, 26443629, 29422019, 17129765); Phenotypes: Progressive vision loss, developmental regression, seizures, ataxia, speech and language difficulties, myoclonus, EEG abnormalities, cerebral atrophy, cerebellar atrophy, autofluorescent lipopigment in neurons, intracellular fingerprint profiles on ultrastructural analysis, intracellular curvilinear profiles on ultrastructural analysis, onset at 2 to 7 years of age, most patients lose ambulation two years after onset.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Myoclonic Epilepsy v0.22 CLN6 Noor Al-Ali reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 21549341, 30561534, 33024953, 34597687); Phenotypes: Seizures, cerebellar ataxia, extrapyramidal signs, myoclonus, dementia, cerebral atrophy, autofluorescent lipopigment in neurons, leukoencephalopathy on CT and MRI, behavioral changes, depression, auditory and visual hallucinations, granular osmiophilic deposits (GROD) in cells resulting in “fingerprint” profiles ultrastructurally, granular osmiophilic deposits (GROD) in cells resulting in “curvilinear” profiles ultrastructurally, granular osmiophilic deposits (GROD) in cells resulting in “rectilinear” profiles ultrastructurally, onset in adulthood (third to fourth decade).; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Myoclonic Epilepsy v0.22 CLN5 Noor Al-Ali reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 20157158, 41003830, 39667065, 22532218, 32983231); Phenotypes: Onset at 4 to 7 years, progressive vision loss, retinal degeneration, nystagmus, clumsiness, motor deterioration, developmental regression, ataxia, dysarthria, dysmetria, dysdiadochokinesis, seizures, myoclonus, intellectual disability, cognitive impairment, neurophysiologic abnormalities (EEG, VEP, SEP), characteristic findings on MRI, autofluorescent lipopigment in neurons, cerebellar atrophy (in one family), concentration difficulties, “fingerprint” profiles ultrastructurally, “curvilinear” profiles ultrastructurally, “rectilinear” profiles ultrastructurally; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Myoclonic Epilepsy v0.22 CLN3 Noor Al-Ali reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 9311735, 24827497, 21990111, 31568712, 30884409); Phenotypes: Onset at 4 to 10 years, progressive vision loss (4 to 10 years), blindness (6 to 14 years), retinitis pigmentosa, macular degeneration, optic atrophy, abolished electroretinogram (ERG), glaucoma, lens-induced, cataract, juvenile-onset mature, concentric hypertrophic cardiomyopathy, severe (later onset in protracted cases), autophagic vacuoles seen on biopsy (in some patients), intermyofibrillar and subsarcolemmal accumulation of electron-dense material (in some patients), psychomotor degeneration, intellectual disability, dementia, extrapyramidal signs, myoclonus, parkinsonism, cerebellar signs, progressive inability to walk, seizures, dysarthria, autofluorescent lipopigment in neurons, cerebral atrophy, difficulty in school, behavioural changes, mood disturbances, anxiety, psychosis, vacuolated lymphocytes, lipopigment in extraneuronal cells, “fingerprint profiles” ultrastructurally in cells, “curvilinear profiles” ultrastructurally in cells.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 UMOD Noor Al-Ali reviewed gene: UMOD: Rating: GREEN; Mode of pathogenicity: Other; Publications: (PMID: 23988501, 12471200, 32954071, 33397327, 23396133, 32450155); Phenotypes: Onset at adolescent or adult age, arterial hypertension (in some patients), renal insufficiency, nephropathy, renal failure, polydipsia, polyuria, impaired urinary concentration, chronic interstitial nephritis, tubulointerstitial abnormalities, tubular atrophy, interstitial fibrosis, hyaline material deposited around tubules, thickening of the basement membrane, medullary cysts (in some patients), glomerulosclerosis (in some patients), glomerulocystic kidney disease (in some patients), dilatation of Bowman’s space in glomeruli, rudimentary glomerular tufts, gout, hyperuricemia, decreased urinary excretion of uromodulin, onset of hyperuricemia or gout in young adulthood, slowly progressive disorder.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 MUC1 Noor Al-Ali reviewed gene: MUC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: (PMID: 23396133, 29967284, 29156055); Phenotypes: Hypertension, impaired renal function, impaired renal creatinine clearance, impaired renal uric acid clearance, salt wasting, small kidneys, tubulointerstitial nephritis, tubulointerstitial fibrosis, interstitial inflammation, glomerulosclerosis, medullary cysts, corticomedullary cysts, tubular atrophy, cortical atrophy, disintegration of the tubular basement membrane, end-stage renal failure, gout, anemia, hyperuricemia, increased serum creatinine, decreased glomerular filtration rate (GFR), adult onset (range 34 to 66 years).; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.91 HNF1B Noor Al-Ali reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: (PMID: 39114399, 38044981, 29576871, 33305128, 25700310, 22432796); Phenotypes: Congenital anomalies of the kidney and urinary tract (CAKUT), chronic renal failure, structural kidney abnormalities, unilateral kidney agenesis, renal cysts, renal hypoplasia, renal parenchymal disease, interstitial fibrosis, cortical atrophy, abnormal nephrogenesis, decreased numbers of glomeruli, enlarged glomeruli, glomerular tufts, glomerular cysts, oligomeganephronia, abnormal renal calyces, abnormal renal pelvises, pelviureteric junction obstruction, hypoplastic glomerulocystic kidney disease, reduced fractional excretion of uric acid, renal calculi, diabetes mellitus, impaired glucose tolerance, glucosuria, proteinuria, increased serum creatinine, hyperuricemia.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.599 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Arthrogryposis v0.599 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.599 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1, MIM# 609308
Arthrogryposis v0.598 POMT1 Zornitza Stark Mode of inheritance for gene: POMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.597 POMT1 Zornitza Stark reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1, MIM# 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v1.103 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Hereditary Spastic Paraplegia v1.103 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Callosome v0.569 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Callosome v0.569 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.273 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Genetic Epilepsy v1.273 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Mendeliome v1.3576 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Mendeliome v1.3576 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.429 RPS6KC1 Zornitza Stark Marked gene: RPS6KC1 as ready
Intellectual disability syndromic and non-syndromic v1.429 RPS6KC1 Zornitza Stark Gene: rps6kc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.273 STARD9 Zornitza Stark Marked gene: STARD9 as ready
Genetic Epilepsy v1.273 STARD9 Zornitza Stark Gene: stard9 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.273 Zornitza Stark Copied gene STARD9 from panel Mendeliome
Genetic Epilepsy v1.273 STARD9 Zornitza Stark gene: STARD9 was added
gene: STARD9 was added to Genetic Epilepsy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: STARD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STARD9 were set to 41137852; 28777490
Phenotypes for gene: STARD9 were set to Syndromic disorder (MONDO:0002254), STARD9-related
Mendeliome v1.3576 STARD9 Zornitza Stark Marked gene: STARD9 as ready
Mendeliome v1.3576 STARD9 Zornitza Stark Gene: stard9 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.597 POMK Zornitza Stark Marked gene: POMK as ready
Arthrogryposis v0.597 POMK Zornitza Stark Gene: pomk has been classified as Green List (High Evidence).
Arthrogryposis v0.597 POMK Zornitza Stark Phenotypes for gene: POMK were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249
Arthrogryposis v0.596 POMK Zornitza Stark Mode of inheritance for gene: POMK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.595 POMK Zornitza Stark reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.595 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Arthrogryposis v0.595 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.595 POMGNT2 Zornitza Stark Phenotypes for gene: POMGNT2 were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135
Arthrogryposis v0.594 POMGNT2 Zornitza Stark Mode of inheritance for gene: POMGNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.593 POMGNT2 Zornitza Stark Classified gene: POMGNT2 as Amber List (moderate evidence)
Arthrogryposis v0.593 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.592 POMGNT2 Zornitza Stark reviewed gene: POMGNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8, MIM# 618135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.592 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Arthrogryposis v0.592 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Arthrogryposis v0.592 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157
Arthrogryposis v0.591 POMGNT1 Zornitza Stark Mode of inheritance for gene: POMGNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.590 POMGNT1 Zornitza Stark reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.590 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
Arthrogryposis v0.590 PLOD2 Zornitza Stark Gene: plod2 has been classified as Green List (High Evidence).
Arthrogryposis v0.590 PLOD2 Zornitza Stark Phenotypes for gene: PLOD2 were changed from to Bruck syndrome 2, MIM# 609220
Arthrogryposis v0.589 PLOD2 Zornitza Stark Publications for gene: PLOD2 were set to
Arthrogryposis v0.588 PLOD2 Zornitza Stark Mode of inheritance for gene: PLOD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.587 Zornitza Stark Added reviews for gene PLOD2 from panel Mendeliome
Skeletal Dysplasia_Fetal v0.240 PLOD2 Zornitza Stark Deleted their review
Skeletal Dysplasia_Fetal v0.240 Zornitza Stark Added reviews for gene PLOD2 from panel Mendeliome
Arthrogryposis v0.586 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
Arthrogryposis v0.586 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.586 PLOD1 Zornitza Stark Phenotypes for gene: PLOD1 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400
Arthrogryposis v0.585 PLOD1 Zornitza Stark Mode of inheritance for gene: PLOD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.584 PLOD1 Zornitza Stark Classified gene: PLOD1 as Red List (low evidence)
Arthrogryposis v0.584 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
Arthrogryposis v0.583 PLOD1 Zornitza Stark reviewed gene: PLOD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.583 PFKM Zornitza Stark Marked gene: PFKM as ready
Arthrogryposis v0.583 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Arthrogryposis v0.583 PFKM Zornitza Stark Phenotypes for gene: PFKM were changed from to Glycogen storage disease VII (MIM#232800)
Arthrogryposis v0.582 PFKM Zornitza Stark Publications for gene: PFKM were set to
Arthrogryposis v0.581 PFKM Zornitza Stark Mode of inheritance for gene: PFKM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.580 PFKM Zornitza Stark reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: None; Publications: 7794557; Phenotypes: Glycogen storage disease VII (MIM#232800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.580 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Arthrogryposis v0.580 PEX7 Zornitza Stark Gene: pex7 has been classified as Green List (High Evidence).
Arthrogryposis v0.580 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from to Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100
Arthrogryposis v0.579 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Arthrogryposis v0.578 PEX7 Zornitza Stark Mode of inheritance for gene: PEX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.577 PEX7 Zornitza Stark reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 11781871; Phenotypes: Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.577 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Arthrogryposis v0.577 PEX6 Zornitza Stark Gene: pex6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.577 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Arthrogryposis v0.576 PEX6 Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.575 PEX6 Zornitza Stark Classified gene: PEX6 as Amber List (moderate evidence)
Arthrogryposis v0.575 PEX6 Zornitza Stark Gene: pex6 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.574 PEX6 Zornitza Stark reviewed gene: PEX6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.574 PEX5 Zornitza Stark Marked gene: PEX5 as ready
Arthrogryposis v0.574 PEX5 Zornitza Stark Gene: pex5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.574 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from to Peroxisome biogenesis disorder 2A (Zellweger) (MIM#214110)
Arthrogryposis v0.573 PEX5 Zornitza Stark Mode of inheritance for gene: PEX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.572 PEX5 Zornitza Stark Classified gene: PEX5 as Amber List (moderate evidence)
Arthrogryposis v0.572 PEX5 Zornitza Stark Gene: pex5 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.571 PEX5 Zornitza Stark reviewed gene: PEX5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger) (MIM#214110); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3576 STARD9 Rylee Peters Classified gene: STARD9 as Amber List (moderate evidence)
Mendeliome v1.3576 STARD9 Rylee Peters Gene: stard9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.429 Rylee Peters Copied gene RPS6KC1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.429 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Hereditary Spastic Paraplegia v1.103 Rylee Peters Copied gene RPS6KC1 from panel Mendeliome
Hereditary Spastic Paraplegia v1.103 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Genetic Epilepsy v1.272 Rylee Peters Copied gene RPS6KC1 from panel Mendeliome
Genetic Epilepsy v1.272 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Callosome v0.569 Rylee Peters Copied gene RPS6KC1 from panel Mendeliome
Callosome v0.569 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Callosome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Mendeliome v1.3575 RPS6KC1 Rylee Peters Classified gene: RPS6KC1 as Green List (high evidence)
Mendeliome v1.3575 RPS6KC1 Rylee Peters Gene: rps6kc1 has been classified as Green List (High Evidence).
Mendeliome v1.3574 RPS6KC1 Rylee Peters gene: RPS6KC1 was added
gene: RPS6KC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS6KC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPS6KC1 were set to 41130203
Phenotypes for gene: RPS6KC1 were set to Complex neurodevelopmental disorder, MONDO:0100038, RPS6KC1-related
Review for gene: RPS6KC1 was set to GREEN
Added comment: PMID: 41130203 | Bi-allelic RPS6KC1 variants identified in 13 individuals from 8 independent families. Phenotypic manifestations included neurodevelopmental delay, epilepsy, hypotonia, spastic paraplegia, brain white matter loss, and dysmorphic features.
Functional studies including a HAP1 cellular model and a Drosophila melanogaster model recapitulated the defects observed in individuals with RPS6KC1 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.428 DOCK4 Zornitza Stark Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to Neurodevelopmental disorder, MONDO:0700092, DOCK4-related
Intellectual disability syndromic and non-syndromic v1.427 DOCK4 Zornitza Stark edited their review of gene: DOCK4: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, DOCK4-related
Mendeliome v1.3573 DOCK4 Zornitza Stark Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to Neurodevelopmental disorder, MONDO:0700092, DOCK4-related
Mendeliome v1.3572 DOCK4 Zornitza Stark reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, DOCK4-related; Mode of inheritance: None
Mendeliome v1.3572 STARD9 Rylee Peters gene: STARD9 was added
gene: STARD9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STARD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STARD9 were set to 41137852; 28777490
Phenotypes for gene: STARD9 were set to Syndromic disorder (MONDO:0002254), STARD9-related
Review for gene: STARD9 was set to AMBER
Added comment: STARD9 enables microtubule binding activity, motor activity and is involved in spindle assembly.

PMID: 41137852 | 1x cHet individual with early-onset febrile seizures followed by atypical absence seizures. The two missense identified, p.(Leu694Phe) and p.(Met3409Val), have 5 hets and 125 hets respectively in gnomAD v4.

PMID: 28777490 | 1x hom individual with a frameshift variant, p.(L3920fs*38). Patient had severe intellectual disability, epilepsy, dysmorphic features, acquired microcephaly, and blindness. Patient cells showed mitotic spindle assembly defects.
Sources: Literature
Severe early-onset obesity v1.20 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092), LRRC7-related to Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Severe early-onset obesity v1.19 LRRC7 Zornitza Stark edited their review of gene: LRRC7: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Intellectual disability syndromic and non-syndromic v1.427 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092), LRRC7-related to Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Intellectual disability syndromic and non-syndromic v1.426 LRRC7 Zornitza Stark edited their review of gene: LRRC7: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Mendeliome v1.3571 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092), LRRC7-related to Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Mendeliome v1.3570 LRRC7 Zornitza Stark edited their review of gene: LRRC7: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 77, MIM# 621415
Arthrogryposis v0.571 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Arthrogryposis v0.571 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Arthrogryposis v0.571 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to Pontocerebellar hypoplasia type 2A, MIM# 277470; Pontocerebellar hypoplasia type 4, MIM# 225753
Arthrogryposis v0.570 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Arthrogryposis v0.569 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.568 TSEN54 Zornitza Stark changed review comment from: Well established gene-disease association.

Individuals homozygous for the common TSEN54 missense mutation A307S are reported to have a phenotype consistent with PCH2, whereas those who were compound heterozygous for A307S and a different TSEN54 mutation have a more severe phenotype consistent with PCH4.; to: Well established gene-disease association.

Individuals homozygous for the common TSEN54 missense mutation A307S are reported to have a phenotype consistent with PCH2, whereas those who were compound heterozygous for A307S and a different TSEN54 mutation have a more severe phenotype consistent with PCH4.

Multiple contractures are part of the phenotype.
Arthrogryposis v0.568 TSEN54 Zornitza Stark edited their review of gene: TSEN54: Changed publications: 18711368, 20956791, 20952379, 20301773
Arthrogryposis v0.568 Zornitza Stark Added reviews for gene TSEN54 from panel Cerebellar and Pontocerebellar Hypoplasia
Arthrogryposis v0.567 PEX3 Zornitza Stark Marked gene: PEX3 as ready
Arthrogryposis v0.567 PEX3 Zornitza Stark Gene: pex3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.567 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from to Peroxisome biogenesis disorder 10A (Zellweger) MIM#614882
Arthrogryposis v0.566 PEX3 Zornitza Stark Mode of inheritance for gene: PEX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.565 PEX3 Zornitza Stark Classified gene: PEX3 as Amber List (moderate evidence)
Arthrogryposis v0.565 PEX3 Zornitza Stark Gene: pex3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.564 PEX3 Zornitza Stark reviewed gene: PEX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger) MIM#614882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.564 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Arthrogryposis v0.564 PEX26 Zornitza Stark Gene: pex26 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.564 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872
Arthrogryposis v0.563 PEX26 Zornitza Stark Mode of inheritance for gene: PEX26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.562 PEX26 Zornitza Stark Classified gene: PEX26 as Amber List (moderate evidence)
Arthrogryposis v0.562 PEX26 Zornitza Stark Gene: pex26 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.561 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.561 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Arthrogryposis v0.561 PEX2 Zornitza Stark Gene: pex2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.561 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from to Peroxisome biogenesis disorder 5A (Zellweger) - MIM#614866
Arthrogryposis v0.560 PEX2 Zornitza Stark Mode of inheritance for gene: PEX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.559 PEX2 Zornitza Stark Classified gene: PEX2 as Amber List (moderate evidence)
Arthrogryposis v0.559 PEX2 Zornitza Stark Gene: pex2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.558 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger) - MIM#614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.558 COL6A3 Zornitza Stark Marked gene: COL6A3 as ready
Arthrogryposis v0.558 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Green List (High Evidence).
Arthrogryposis v0.558 COL6A3 Zornitza Stark Phenotypes for gene: COL6A3 were changed from to Bethlem myopathy, MIM#158810; Ullrich congenital muscular dystrophy, MIM#254090
Arthrogryposis v0.557 COL6A3 Zornitza Stark Publications for gene: COL6A3 were set to
Arthrogryposis v0.556 COL6A3 Zornitza Stark Mode of inheritance for gene: COL6A3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.555 COL6A3 Zornitza Stark changed review comment from: Well established gene.
Sources: Expert list; to: Well established gene-disease associations, contractures are a feature of both.
Sources: Expert list
Arthrogryposis v0.555 Zornitza Stark Added reviews for gene COL6A3 from panel Myopathy - paediatric onset
Arthrogryposis v0.554 COL6A1 Zornitza Stark Marked gene: COL6A1 as ready
Arthrogryposis v0.554 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Green List (High Evidence).
Arthrogryposis v0.554 COL6A1 Zornitza Stark Phenotypes for gene: COL6A1 were changed from to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090
Arthrogryposis v0.553 COL6A1 Zornitza Stark Publications for gene: COL6A1 were set to
Arthrogryposis v0.552 COL6A1 Zornitza Stark Mode of inheritance for gene: COL6A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arthrogryposis v0.551 Zornitza Stark Added reviews for gene COL6A1 from panel Mendeliome
Arthrogryposis v0.550 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arthrogryposis v0.550 COL6A2 Zornitza Stark Marked gene: COL6A2 as ready
Arthrogryposis v0.550 COL6A2 Zornitza Stark Gene: col6a2 has been classified as Green List (High Evidence).
Arthrogryposis v0.550 COL6A2 Zornitza Stark Phenotypes for gene: COL6A2 were changed from to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090
Arthrogryposis v0.549 COL6A2 Zornitza Stark Publications for gene: COL6A2 were set to
Arthrogryposis v0.548 COL6A2 Zornitza Stark Mode of inheritance for gene: COL6A2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arthrogryposis v0.547 Zornitza Stark Added reviews for gene COL6A2 from panel Mendeliome
Arthrogryposis v0.546 COL6A2 Zornitza Stark reviewed gene: COL6A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Arthrogryposis v0.546 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Arthrogryposis v0.546 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Arthrogryposis v0.546 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from to Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886
Arthrogryposis v0.545 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Arthrogryposis v0.544 PEX19 Zornitza Stark Mode of inheritance for gene: PEX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.543 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 36931687; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.543 PEX16 Zornitza Stark Marked gene: PEX16 as ready
Arthrogryposis v0.543 PEX16 Zornitza Stark Gene: pex16 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.543 PEX16 Zornitza Stark Phenotypes for gene: PEX16 were changed from to Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876
Arthrogryposis v0.542 PEX16 Zornitza Stark Mode of inheritance for gene: PEX16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.541 PEX16 Zornitza Stark Classified gene: PEX16 as Amber List (moderate evidence)
Arthrogryposis v0.541 PEX16 Zornitza Stark Gene: pex16 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.540 PEX16 Zornitza Stark reviewed gene: PEX16: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.540 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Arthrogryposis v0.540 PEX14 Zornitza Stark Gene: pex14 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.540 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from to Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876
Arthrogryposis v0.539 PEX14 Zornitza Stark Mode of inheritance for gene: PEX14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.538 PEX14 Zornitza Stark Classified gene: PEX14 as Amber List (moderate evidence)
Arthrogryposis v0.538 PEX14 Zornitza Stark Gene: pex14 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.537 PEX14 Zornitza Stark reviewed gene: PEX14: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger) MIM#614876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.537 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Arthrogryposis v0.537 PEX13 Zornitza Stark Gene: pex13 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.537 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from to Peroxisome biogenesis disorder 11A (Zellweger) (MIM#614883)
Arthrogryposis v0.536 PEX13 Zornitza Stark Mode of inheritance for gene: PEX13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.535 PEX13 Zornitza Stark Classified gene: PEX13 as Amber List (moderate evidence)
Arthrogryposis v0.535 PEX13 Zornitza Stark Gene: pex13 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.534 PEX13 Zornitza Stark reviewed gene: PEX13: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11A (Zellweger) (MIM#614883); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.534 PEX11B Zornitza Stark Classified gene: PEX11B as Amber List (moderate evidence)
Arthrogryposis v0.534 PEX11B Zornitza Stark Gene: pex11b has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.533 PEX11B Zornitza Stark changed review comment from: Comment when marking as ready: Two published families and one internal. Contractures not specifically reported but included with Green rating for completeness together with other severe peroxisomal disorders.; to: Two published families and one internal. Contractures not specifically reported hence Amber rating given other severe peroxisomal disorders are reported with talipes.
Arthrogryposis v0.533 PEX11B Zornitza Stark edited their review of gene: PEX11B: Changed rating: AMBER
Arthrogryposis v0.533 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Arthrogryposis v0.533 PEX12 Zornitza Stark Gene: pex12 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.533 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859
Arthrogryposis v0.532 PEX12 Zornitza Stark Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.531 PEX12 Zornitza Stark Classified gene: PEX12 as Amber List (moderate evidence)
Arthrogryposis v0.531 PEX12 Zornitza Stark Gene: pex12 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.530 PEX12 Zornitza Stark changed review comment from: Well established gene-disease association, varus deformity reported but no specific reports of contractures/arthrogryposis.; to: Well established gene-disease association, varus deformity reported but no specific reports of contractures/arthrogryposis. Other severe peroxisomal disorders reported with talipes hence Amber rating.
Arthrogryposis v0.530 PEX12 Zornitza Stark edited their review of gene: PEX12: Changed rating: AMBER
Arthrogryposis v0.530 PEX12 Zornitza Stark changed review comment from: Well established gene-disease association, varus deformity reported.; to: Well established gene-disease association, varus deformity reported but no specific reports of contractures/arthrogryposis.
Arthrogryposis v0.530 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.530 PEX11B Zornitza Stark Marked gene: PEX11B as ready
Arthrogryposis v0.530 PEX11B Zornitza Stark Gene: pex11b has been classified as Green List (High Evidence).
Arthrogryposis v0.530 PEX11B Zornitza Stark Phenotypes for gene: PEX11B were changed from to Peroxisome biogenesis disorder 14B - MIM#614920
Arthrogryposis v0.529 PEX11B Zornitza Stark Publications for gene: PEX11B were set to
Arthrogryposis v0.528 PEX11B Zornitza Stark Mode of inheritance for gene: PEX11B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.527 PEX11B Zornitza Stark changed review comment from: Comment when marking as ready: Two published families and one internal.; to: Comment when marking as ready: Two published families and one internal. Contractures not specifically reported but included with Green rating for completeness together with other severe peroxisomal disorders.
Arthrogryposis v0.527 Zornitza Stark Added reviews for gene PEX11B from panel Mendeliome
Mendeliome v1.3570 PEX11B Zornitza Stark changed review comment from: Comment when marking as ready: Two published families and one International.; to: Comment when marking as ready: Two published families and one internal.
Arthrogryposis v0.526 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Arthrogryposis v0.526 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Arthrogryposis v0.526 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from to Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870
Arthrogryposis v0.525 PEX10 Zornitza Stark Mode of inheritance for gene: PEX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.524 PEX10 Zornitza Stark reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) 614870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.524 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Arthrogryposis v0.524 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Arthrogryposis v0.524 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100
Arthrogryposis v0.523 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.522 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v2.15 ORAI1 Zornitza Stark Phenotypes for gene: ORAI1 were changed from Immunodeficiency 9, MIM#612782; Myopathy, tubular aggregate, 2, MIM#615883 to Immunodeficiency 9, MIM#612782
Prepair 1000+ v2.14 ORAI1 Zornitza Stark reviewed gene: ORAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 9, MIM#612782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.522 ORAI1 Zornitza Stark Marked gene: ORAI1 as ready
Arthrogryposis v0.522 ORAI1 Zornitza Stark Gene: orai1 has been classified as Green List (High Evidence).
Arthrogryposis v0.522 ORAI1 Zornitza Stark Phenotypes for gene: ORAI1 were changed from to Myopathy, tubular aggregate, 2, MIM# 615883
Arthrogryposis v0.521 ORAI1 Zornitza Stark Publications for gene: ORAI1 were set to
Arthrogryposis v0.520 ORAI1 Zornitza Stark Mode of inheritance for gene: ORAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.519 ORAI1 Zornitza Stark changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)

Contractures are part of the phenotype, e.g. PMID 25227914
Arthrogryposis v0.519 ORAI1 Zornitza Stark edited their review of gene: ORAI1: Changed publications: 31448844, 25227914
Arthrogryposis v0.519 Zornitza Stark Added reviews for gene ORAI1 from panel Muscular dystrophy and myopathy_Paediatric
Macrocephaly_Megalencephaly v0.152 KLHL13 Zornitza Stark Marked gene: KLHL13 as ready
Macrocephaly_Megalencephaly v0.152 KLHL13 Zornitza Stark Gene: klhl13 has been classified as Green List (High Evidence).
Ataxia v1.62 Zornitza Stark removed gene:KLHL13 from the panel
Muscular dystrophy and myopathy_Paediatric v1.110 Zornitza Stark removed gene:KLHL13 from the panel
Arthrogryposis v0.518 MYH8 Zornitza Stark Marked gene: MYH8 as ready
Arthrogryposis v0.518 MYH8 Zornitza Stark Gene: myh8 has been classified as Green List (High Evidence).
Arthrogryposis v0.518 MYH8 Zornitza Stark Phenotypes for gene: MYH8 were changed from to Trismus-pseudocamptodactyly syndrome (MIM#158300)
Arthrogryposis v0.517 MYH8 Zornitza Stark Publications for gene: MYH8 were set to
Arthrogryposis v0.516 MYH8 Zornitza Stark Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.515 Zornitza Stark Added reviews for gene MYH8 from panel Fetal anomalies
Arthrogryposis v0.514 MYH3 Zornitza Stark Marked gene: MYH3 as ready
Arthrogryposis v0.514 MYH3 Zornitza Stark Gene: myh3 has been classified as Green List (High Evidence).
Arthrogryposis v0.514 MYH3 Zornitza Stark Phenotypes for gene: MYH3 were changed from to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469
Arthrogryposis v0.513 MYH3 Zornitza Stark Publications for gene: MYH3 were set to
Arthrogryposis v0.512 MYH3 Zornitza Stark Mode of inheritance for gene: MYH3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.511 Zornitza Stark Added reviews for gene MYH3 from panel Myopathy - paediatric onset
Arthrogryposis v0.510 MUSK Zornitza Stark Marked gene: MUSK as ready
Arthrogryposis v0.510 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Arthrogryposis v0.510 MUSK Zornitza Stark Phenotypes for gene: MUSK were changed from to Fetal akinesia deformation sequence 1, MIM# 208150; MONDO:0100101
Arthrogryposis v0.509 MUSK Zornitza Stark Publications for gene: MUSK were set to
Arthrogryposis v0.508 MUSK Zornitza Stark Mode of inheritance for gene: MUSK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.507 MUSK Zornitza Stark changed review comment from: At least 3 unrelated families reported.; to: At least 3 unrelated families reported. Contractures are part of the phenotype.
Arthrogryposis v0.507 Zornitza Stark Added reviews for gene MUSK from panel Multiple pterygium syndrome_Fetal akinesia sequence
Arthrogryposis v0.506 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Arthrogryposis v0.506 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Arthrogryposis v0.506 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from to X-linked myotubular myopathy MONDO:0010683
Arthrogryposis v0.505 MTM1 Zornitza Stark Mode of inheritance for gene: MTM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.504 MTM1 Zornitza Stark reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked myotubular myopathy MONDO:0010683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.504 LARGE1 Zornitza Stark Marked gene: LARGE1 as ready
Arthrogryposis v0.504 LARGE1 Zornitza Stark Gene: large1 has been classified as Green List (High Evidence).
Arthrogryposis v0.504 LARGE1 Zornitza Stark Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154
Arthrogryposis v0.503 LARGE1 Zornitza Stark Mode of inheritance for gene: LARGE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.502 LARGE1 Zornitza Stark reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.502 FKTN Zornitza Stark Marked gene: FKTN as ready
Arthrogryposis v0.502 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Arthrogryposis v0.502 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, MIM# 253800
Arthrogryposis v0.501 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.500 FKTN Zornitza Stark reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, MIM# 253800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.500 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Arthrogryposis v0.500 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Arthrogryposis v0.500 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350)
Arthrogryposis v0.499 GMPPB Zornitza Stark Mode of inheritance for gene: GMPPB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.498 GMPPB Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.498 FLNB Zornitza Stark Marked gene: FLNB as ready
Arthrogryposis v0.498 FLNB Zornitza Stark Gene: flnb has been classified as Green List (High Evidence).
Arthrogryposis v0.498 FLNB Zornitza Stark Phenotypes for gene: FLNB were changed from to filamin-related bone disorder MONDO:0019690
Arthrogryposis v0.497 FLNB Zornitza Stark Mode of inheritance for gene: FLNB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.496 FLNB Zornitza Stark reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: filamin-related bone disorder MONDO:0019690; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v0.496 GBA Zornitza Stark Marked gene: GBA as ready
Arthrogryposis v0.496 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Arthrogryposis v0.496 GBA Zornitza Stark Phenotypes for gene: GBA were changed from to Gaucher disease, perinatal lethal,MIM# 608013
Arthrogryposis v0.495 GBA Zornitza Stark Publications for gene: GBA were set to
Arthrogryposis v0.494 GBA Zornitza Stark Mode of inheritance for gene: GBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.493 GBA Zornitza Stark edited their review of gene: GBA: Changed phenotypes: Gaucher disease, perinatal lethal,MIM# 608013
Arthrogryposis v0.493 GBA Zornitza Stark reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31192173; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3570 KLHL13 Krithika Murali Phenotypes for gene: KLHL13 were changed from HMSN to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Mendeliome v1.3569 KLHL13 Krithika Murali Publications for gene: KLHL13 were set to 24627108
Mendeliome v1.3568 KLHL13 Krithika Murali Classified gene: KLHL13 as Green List (high evidence)
Mendeliome v1.3568 KLHL13 Krithika Murali Gene: klhl13 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.109 Krithika Murali Copied gene KLHL13 from panel Intellectual disability syndromic and non-syndromic
Muscular dystrophy and myopathy_Paediatric v1.109 KLHL13 Krithika Murali gene: KLHL13 was added
gene: KLHL13 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KLHL13 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: KLHL13 were set to PMID: 41159445
Phenotypes for gene: KLHL13 were set to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Mendeliome v1.3567 Krithika Murali Added reviews for gene KLHL13 from panel Intellectual disability syndromic and non-syndromic
Macrocephaly_Megalencephaly v0.152 Krithika Murali Copied gene KLHL13 from panel Intellectual disability syndromic and non-syndromic
Macrocephaly_Megalencephaly v0.152 KLHL13 Krithika Murali gene: KLHL13 was added
gene: KLHL13 was added to Macrocephaly_Megalencephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KLHL13 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: KLHL13 were set to PMID: 41159445
Phenotypes for gene: KLHL13 were set to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Ataxia v1.61 Krithika Murali Copied gene KLHL13 from panel Intellectual disability syndromic and non-syndromic
Ataxia v1.61 KLHL13 Krithika Murali gene: KLHL13 was added
gene: KLHL13 was added to Ataxia - paediatric. Sources: Expert Review Green,Literature
Mode of inheritance for gene: KLHL13 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: KLHL13 were set to PMID: 41159445
Phenotypes for gene: KLHL13 were set to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Intellectual disability syndromic and non-syndromic v1.426 KLHL13 Krithika Murali Classified gene: KLHL13 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.426 KLHL13 Krithika Murali Gene: klhl13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.425 KLHL13 Krithika Murali Marked gene: KLHL13 as ready
Intellectual disability syndromic and non-syndromic v1.425 KLHL13 Krithika Murali Gene: klhl13 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.425 KLHL13 Krithika Murali gene: KLHL13 was added
gene: KLHL13 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KLHL13 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: KLHL13 were set to PMID: 41159445
Phenotypes for gene: KLHL13 were set to Neurodevelopmental disorder, MONDO:0700092, KLHL13-related
Review for gene: KLHL13 was set to GREEN
Added comment: PMID: 41159445 Akhther et al 2025 (pre-print) report 8 affected individuals from 4 unrelated famlies with hemizygous/heterozygous KLHL13 variants and an X-linked neurodevelopmental disorder with the following phenotypic features including mild-severe ID, developmental delay, macrocephaly, hypotonia, unsteady gait, facial dysmrophism and behavioural issues. Functional studies support LoF disease mechanism.
Sources: Literature
Arthrogryposis v0.493 LGI4 Zornitza Stark Marked gene: LGI4 as ready
Arthrogryposis v0.493 LGI4 Zornitza Stark Gene: lgi4 has been classified as Green List (High Evidence).
Arthrogryposis v0.493 LGI4 Zornitza Stark Phenotypes for gene: LGI4 were changed from to Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468
Arthrogryposis v0.492 LGI4 Zornitza Stark Publications for gene: LGI4 were set to
Arthrogryposis v0.491 LGI4 Zornitza Stark Mode of inheritance for gene: LGI4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.490 Zornitza Stark Added reviews for gene LGI4 from panel Mendeliome
Arthrogryposis v0.489 CHRNG Zornitza Stark Source Victorian Clinical Genetics Services was removed from CHRNG.
Source Literature was added to CHRNG.
Phenotypes for gene: CHRNG were changed from Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009926; MONDO:0009668 to Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009668
Arthrogryposis v0.488 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Arthrogryposis v0.488 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Arthrogryposis v0.488 GBE1 Zornitza Stark Phenotypes for gene: GBE1 were changed from to Glycogen storage disease IV, MIM# 232500
Arthrogryposis v0.487 GBE1 Zornitza Stark Publications for gene: GBE1 were set to
Arthrogryposis v0.486 GBE1 Zornitza Stark Mode of inheritance for gene: GBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.485 GBE1 Zornitza Stark changed review comment from: Glycogen storage disease type IV is a clinically heterogeneous disorder. The typical 'classic' hepatic presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular presentation of GSD IV is distinguished by age at onset into 4 groups: perinatal, presenting as fetal akinesia deformation sequence (FADS) and perinatal death; congenital, with hypotonia, neuronal involvement, and death in early infancy; childhood, with myopathy or cardiomyopathy; and adult, with isolated myopathy or adult polyglucosan body disease.

Established gene-disease association.; to: Glycogen storage disease type IV is a clinically heterogeneous disorder. The typical 'classic' hepatic presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular presentation of GSD IV is distinguished by age at onset into 4 groups: perinatal, presenting as fetal akinesia deformation sequence (FADS) and perinatal death; congenital, with hypotonia, neuronal involvement, and death in early infancy; childhood, with myopathy or cardiomyopathy; and adult, with isolated myopathy or adult polyglucosan body disease.

Established gene-disease association.

Perinatal neuromuscular presentation is pertinent to this panel.
Arthrogryposis v0.485 Zornitza Stark Added reviews for gene GBE1 from panel Glycogen Storage Diseases
Arthrogryposis v0.484 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Arthrogryposis v0.484 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Arthrogryposis v0.484 IRF6 Zornitza Stark Phenotypes for gene: IRF6 were changed from to Popliteal pterygium syndrome 1MIM#119500
Arthrogryposis v0.483 IRF6 Zornitza Stark Mode of inheritance for gene: IRF6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.482 IRF6 Zornitza Stark reviewed gene: IRF6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Popliteal pterygium syndrome 1MIM#119500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.482 ISPD Zornitza Stark Marked gene: ISPD as ready
Arthrogryposis v0.482 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Arthrogryposis v0.482 ISPD Zornitza Stark Phenotypes for gene: ISPD were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052
Arthrogryposis v0.481 ISPD Zornitza Stark Publications for gene: ISPD were set to
Arthrogryposis v0.480 ISPD Zornitza Stark Mode of inheritance for gene: ISPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.479 ISPD Zornitza Stark changed review comment from: Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. A milder phenotype, presenting with limb-girdle muscular dystrophy has also been reported with bi-allelic variants in this gene.; to: Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. A milder phenotype, presenting with limb-girdle muscular dystrophy has also been reported with bi-allelic variants in this gene.

Contractures are part of the phenotype.
Arthrogryposis v0.479 ISPD Zornitza Stark Tag new gene name tag was added to gene: ISPD.
Arthrogryposis v0.479 Zornitza Stark Added reviews for gene ISPD from panel Mendeliome
Arthrogryposis v0.478 FKRP Zornitza Stark Marked gene: FKRP as ready
Arthrogryposis v0.478 FKRP Zornitza Stark Gene: fkrp has been classified as Green List (High Evidence).
Arthrogryposis v0.478 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 MIM#613153; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 MIM#606612; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 MIM#607155
Arthrogryposis v0.477 FKRP Zornitza Stark Publications for gene: FKRP were set to
Arthrogryposis v0.476 FKRP Zornitza Stark Mode of inheritance for gene: FKRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.475 FKRP Zornitza Stark reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11592034; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 MIM#613153, Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 MIM#606612, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 MIM#607155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.475 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
Arthrogryposis v0.475 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Arthrogryposis v0.475 FKBP10 Zornitza Stark Phenotypes for gene: FKBP10 were changed from to Bruck syndrome 1 MIM#259450
Arthrogryposis v0.474 FKBP10 Zornitza Stark Mode of inheritance for gene: FKBP10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.473 FKBP10 Zornitza Stark reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bruck syndrome 1 MIM#259450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.473 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Arthrogryposis v0.473 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Arthrogryposis v0.473 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, MIM# 207410
Arthrogryposis v0.472 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.471 FGFR2 Zornitza Stark reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, MIM# 207410; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.471 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Arthrogryposis v0.471 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.471 FGFR3 Zornitza Stark Classified gene: FGFR3 as Red List (low evidence)
Arthrogryposis v0.471 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.470 FGFR3 Zornitza Stark reviewed gene: FGFR3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Arthrogryposis v0.470 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Arthrogryposis v0.470 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.470 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Arthrogryposis v0.469 EXOSC3 Zornitza Stark Publications for gene: EXOSC3 were set to
Arthrogryposis v0.468 EXOSC3 Zornitza Stark Mode of inheritance for gene: EXOSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.467 EXOSC3 Zornitza Stark Classified gene: EXOSC3 as Red List (low evidence)
Arthrogryposis v0.467 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Red List (Low Evidence).
Arthrogryposis v0.466 EXOSC3 Zornitza Stark reviewed gene: EXOSC3: Rating: RED; Mode of pathogenicity: None; Publications: 23284067; Phenotypes: Pontocerebellar hypoplasia, type 1B, MIM# 614678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.424 QSER1 Zornitza Stark Source Literature was added to QSER1.
Rating Changed from No List (delete) to Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.423 QSER1 Zornitza Stark All sources for gene: QSER1 were removed
Intellectual disability syndromic and non-syndromic v1.422 QSER1 Zornitza Stark All sources for gene: QSER1 were removed
Autoinflammatory Disorders v2.30 QSER1 Zornitza Stark Marked gene: QSER1 as ready
Autoinflammatory Disorders v2.30 QSER1 Zornitza Stark Gene: qser1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.271 NOL10 Zornitza Stark Marked gene: NOL10 as ready
Genetic Epilepsy v1.271 NOL10 Zornitza Stark Gene: nol10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.271 Zornitza Stark Copied gene NOL10 from panel Mendeliome
Genetic Epilepsy v1.271 NOL10 Zornitza Stark gene: NOL10 was added
gene: NOL10 was added to Genetic Epilepsy. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NOL10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOL10 were set to 41093997
Phenotypes for gene: NOL10 were set to NOL10-related neurological disorder MONDO:0100545
Mendeliome v1.3566 NOL10 Zornitza Stark Marked gene: NOL10 as ready
Mendeliome v1.3566 NOL10 Zornitza Stark Gene: nol10 has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v1.24 CASP1 Zornitza Stark Phenotypes for gene: CASP1 were changed from Absent IL18 and lymphopenia but no clinical disease to Inborn error of immunity, MONDO:0003778, CASP1-related; Absent IL18 and lymphopenia but no clinical disease
Mendeliome v1.3566 CASP1 Zornitza Stark Phenotypes for gene: CASP1 were changed from Absent IL18 and lymphopenia but no clinical disease to Inborn error of immunity, MONDO:0003778, CASP1-related; Absent IL18 and lymphopenia but no clinical disease
Genetic Epilepsy v1.270 BAIAP2 Zornitza Stark Marked gene: BAIAP2 as ready
Genetic Epilepsy v1.270 BAIAP2 Zornitza Stark Gene: baiap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.347 HDAC6 Zornitza Stark Marked gene: HDAC6 as ready
Skeletal dysplasia v0.347 HDAC6 Zornitza Stark Gene: hdac6 has been classified as Red List (Low Evidence).
Mendeliome v1.3565 UNC119 Zornitza Stark Publications for gene: UNC119 were set to 11006213; 23563732; 27079236; 22184408
Mendeliome v1.3564 UNC119 Zornitza Stark edited their review of gene: UNC119: Added comment: PMID 41107067: another mouse model to support the association with cone-rod dystrophy.; Changed publications: 22184408, 41107067
Cone-rod Dystrophy v0.58 UNC119 Zornitza Stark Publications for gene: UNC119 were set to 30679166; 11006213; 23563732; 27079236
Cone-rod Dystrophy v0.57 UNC119 Zornitza Stark edited their review of gene: UNC119: Added comment: PMID 41107067: another mouse model publication to support this gene-disease association.; Changed publications: 41107067
Skeletal dysplasia v0.347 Bryony Thompson Copied gene HDAC6 from panel Mendeliome
Skeletal dysplasia v0.347 HDAC6 Bryony Thompson gene: HDAC6 was added
gene: HDAC6 was added to Skeletal dysplasia. Sources: Expert Review Red,Literature
Mode of inheritance for gene: HDAC6 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: HDAC6 were set to 20181727
Phenotypes for gene: HDAC6 were set to chondrodysplasia MONDO:0022723
Miscellaneous Metabolic Disorders v1.59 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Miscellaneous Metabolic Disorders v1.59 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3564 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Mendeliome v1.3564 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3564 HDAC6 Bryony Thompson Marked gene: HDAC6 as ready
Mendeliome v1.3564 HDAC6 Bryony Thompson Gene: hdac6 has been classified as Red List (Low Evidence).
Mendeliome v1.3564 HDAC6 Bryony Thompson gene: HDAC6 was added
gene: HDAC6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HDAC6 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: HDAC6 were set to 20181727
Phenotypes for gene: HDAC6 were set to chondrodysplasia MONDO:0022723
Review for gene: HDAC6 was set to RED
Added comment: PMID 20181727 reports eight individuals from a single unrelated family with X-linked dominant chondrodysplasia caused by a 3′‑UTR HDAC6 variant (c.*281A>T) that abolishes miR‑433 regulation, leading to HDAC6 overexpression; severe skeletal anomalies are seen in males and a milder asymmetric short‑limb phenotype in heterozygous females. Functional assays in MG63 cells and fetal tissues confirm loss of miRNA‑mediated repression.
Sources: Literature
Fetal anomalies v1.470 NAA16 Zornitza Stark Marked gene: NAA16 as ready
Fetal anomalies v1.470 NAA16 Zornitza Stark Gene: naa16 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.470 Zornitza Stark Copied gene NAA16 from panel Congenital Heart Defect
Fetal anomalies v1.470 NAA16 Zornitza Stark gene: NAA16 was added
gene: NAA16 was added to Fetal anomalies. Sources: Expert Review Amber,Literature,Literature
Mode of inheritance for gene: NAA16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA16 were set to 41148812; 23665959; 28991257
Phenotypes for gene: NAA16 were set to Congenital heart disease, MONDO:0005453, NAA16-related
Congenital Heart Defect v0.478 NAA16 Zornitza Stark Marked gene: NAA16 as ready
Congenital Heart Defect v0.478 NAA16 Zornitza Stark Gene: naa16 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3563 NAA16 Zornitza Stark Marked gene: NAA16 as ready
Mendeliome v1.3563 NAA16 Zornitza Stark Gene: naa16 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v2.30 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related to Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Autoinflammatory Disorders v2.29 OAS2 Zornitza Stark edited their review of gene: OAS2: Changed phenotypes: Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Susceptibility to Viral Infections v1.4 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related to Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Susceptibility to Viral Infections v1.3 OAS2 Zornitza Stark edited their review of gene: OAS2: Changed phenotypes: Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Defects of intrinsic and innate immunity v1.23 OAS2 Zornitza Stark Marked gene: OAS2 as ready
Defects of intrinsic and innate immunity v1.23 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.23 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related to Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Defects of intrinsic and innate immunity v1.22 OAS2 Zornitza Stark edited their review of gene: OAS2: Changed phenotypes: Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Mendeliome v1.3563 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related to Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Mendeliome v1.3562 OAS2 Zornitza Stark edited their review of gene: OAS2: Changed phenotypes: Autoinflammation and autoimmunity, systemic, with immune dysregulation 2, MIM# 621409
Intellectual disability syndromic and non-syndromic v1.421 BAIAP2 Bryony Thompson Marked gene: BAIAP2 as ready
Intellectual disability syndromic and non-syndromic v1.421 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v1.27 BAIAP2 Bryony Thompson Marked gene: BAIAP2 as ready
Lissencephaly and Band Heterotopia v1.27 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.27 BAIAP2 Bryony Thompson Classified gene: BAIAP2 as Red List (low evidence)
Lissencephaly and Band Heterotopia v1.27 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.26 Bryony Thompson Added reviews for gene BAIAP2 from panel Mendeliome
Lissencephaly and Band Heterotopia v1.25 BAIAP2 Bryony Thompson edited their review of gene: BAIAP2: Changed rating: RED
Lissencephaly and Band Heterotopia v1.25 BAIAP2 Bryony Thompson changed review comment from: The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein.
6 individuals with de novo GoF missense variants with DEE. Only 1 individual reported with a LoF missense variant & lissencephaly.
PMID: 41133935 - Reports 6 individuals from 6 unrelated families with heterozygous de novo missense BAIAP2 variants presenting with developmental and epileptic encephalopathy (DEE). Core phenotype: infantile/early‑childhood onset refractory seizures, severe language and motor delay, intellectual disability. All patients have detailed clinical descriptions; variants cluster in the phosphorylation‑rich autoinhibited region. Functional assays (HeLa cell spreading, primary hippocampal neuron electrophysiology, zebrafish overexpression) demonstrate gain‑of‑function effects. No benign variants reported; variants absent from gnomAD.
PMID: 38149472 - Reports 1 individual from 1 family with a de novo heterozygous BAIAP2 missense variant p.Arg29Trp (4 hets in gnomAD v4.1) presenting with classical lissencephaly (posterior>anterior gradient), severe global developmental delay and refractory epilepsy. Mouse Baiap2 knockdown reproduces neuronal migration defects; the p.Arg29Trp variant fails to rescue and shows reduced membrane localization, indicating a loss‑of‑function effect.
Sources: Literature; to: Only 1 individual reported with a LoF missense variant & lissencephaly. More cases are required to confirm GDA.
The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein.
PMID: 41133935 - Reports 6 individuals from 6 unrelated families with heterozygous de novo missense BAIAP2 variants presenting with developmental and epileptic encephalopathy (DEE). Core phenotype: infantile/early‑childhood onset refractory seizures, severe language and motor delay, intellectual disability. All patients have detailed clinical descriptions; variants cluster in the phosphorylation‑rich autoinhibited region. Functional assays (HeLa cell spreading, primary hippocampal neuron electrophysiology, zebrafish overexpression) demonstrate gain‑of‑function effects. No benign variants reported; variants absent from gnomAD.
PMID: 38149472 - Reports 1 individual from 1 family with a de novo heterozygous BAIAP2 missense variant p.Arg29Trp (4 hets in gnomAD v4.1) presenting with classical lissencephaly (posterior>anterior gradient), severe global developmental delay and refractory epilepsy. Mouse Baiap2 knockdown reproduces neuronal migration defects; the p.Arg29Trp variant fails to rescue and shows reduced membrane localization, indicating a loss‑of‑function effect.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.421 Bryony Thompson Added reviews for gene BAIAP2 from panel Mendeliome
Genetic Epilepsy v1.268 Bryony Thompson Copied gene BAIAP2 from panel Mendeliome
Genetic Epilepsy v1.268 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Lissencephaly and Band Heterotopia v1.25 Bryony Thompson Copied gene BAIAP2 from panel Mendeliome
Lissencephaly and Band Heterotopia v1.25 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Lissencephaly and Band Heterotopia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Intellectual disability syndromic and non-syndromic v1.420 Bryony Thompson Copied gene BAIAP2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.420 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Genetic Epilepsy v1.268 Bryony Thompson Copied gene BAIAP2 from panel Mendeliome
Genetic Epilepsy v1.268 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Mendeliome v1.3562 BAIAP2 Bryony Thompson Marked gene: BAIAP2 as ready
Mendeliome v1.3562 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Green List (High Evidence).
Mendeliome v1.3562 BAIAP2 Bryony Thompson Classified gene: BAIAP2 as Green List (high evidence)
Mendeliome v1.3562 BAIAP2 Bryony Thompson Gene: baiap2 has been classified as Green List (High Evidence).
Mendeliome v1.3561 BAIAP2 Bryony Thompson gene: BAIAP2 was added
gene: BAIAP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAIAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAIAP2 were set to 41133935; 38149472
Phenotypes for gene: BAIAP2 were set to BAIAP2-related complex neurodevelopmental disorder MONDO:0100038
Review for gene: BAIAP2 was set to GREEN
Added comment: The protein encoded by this gene has been identified as a brain-specific angiogenesis inhibitor (BAI1)-binding protein.
6 individuals with de novo GoF missense variants with DEE. Only 1 individual reported with a LoF missense variant & lissencephaly.
PMID: 41133935 - Reports 6 individuals from 6 unrelated families with heterozygous de novo missense BAIAP2 variants presenting with developmental and epileptic encephalopathy (DEE). Core phenotype: infantile/early‑childhood onset refractory seizures, severe language and motor delay, intellectual disability. All patients have detailed clinical descriptions; variants cluster in the phosphorylation‑rich autoinhibited region. Functional assays (HeLa cell spreading, primary hippocampal neuron electrophysiology, zebrafish overexpression) demonstrate gain‑of‑function effects. No benign variants reported; variants absent from gnomAD.
PMID: 38149472 - Reports 1 individual from 1 family with a de novo heterozygous BAIAP2 missense variant p.Arg29Trp (4 hets in gnomAD v4.1) presenting with classical lissencephaly (posterior>anterior gradient), severe global developmental delay and refractory epilepsy. Mouse Baiap2 knockdown reproduces neuronal migration defects; the p.Arg29Trp variant fails to rescue and shows reduced membrane localization, indicating a loss‑of‑function effect.
Sources: Literature
Miscellaneous Metabolic Disorders v1.59 TXNIP Lucy Spencer Classified gene: TXNIP as Amber List (moderate evidence)
Miscellaneous Metabolic Disorders v1.59 TXNIP Lucy Spencer Gene: txnip has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3560 TXNIP Lucy Spencer Classified gene: TXNIP as Amber List (moderate evidence)
Mendeliome v1.3560 TXNIP Lucy Spencer Gene: txnip has been classified as Amber List (Moderate Evidence).
Miscellaneous Metabolic Disorders v1.58 Lucy Spencer Copied gene TXNIP from panel Mendeliome
Miscellaneous Metabolic Disorders v1.58 TXNIP Lucy Spencer gene: TXNIP was added
gene: TXNIP was added to Miscellaneous Metabolic Disorders. Sources: Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Mendeliome v1.3559 TXNIP Lucy Spencer gene: TXNIP was added
gene: TXNIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Review for gene: TXNIP was set to AMBER
Added comment: TXNIP binds and inhibits TXN, controlling its activity. The TXN system is a major cellular system for control of redox state, antioxidant defense, and several signaling pathways. TXNIP can also activate the NLRP3 inflammasome and suppress of the activities of the
nuclear factor (erythroid-derived 2)–like 2 (Nrf2) transcription factor.

PMID 30755400 reports three affected siblings from a consanguineous Libyan family with autosomal recessive congenital lactic acidosis and low serum methionine. 2 of the three siblings have developed normally and appear to be mostly asymptomatic apart from variable hypoglycaemia, while the third had failure the thrive as an infant, slow development, ?autism, and slight muscular hypotonus. All three siblings were homozygous for TXNIP c.174_175delinsTT which creates a stopgain at p.Gly59* (and a missense at p.58). Patient‑derived fibroblasts and myoblasts show impaired pyruvate‑driven mitochondrial respiration that is rescued by TXNIP re‑constitution. However, patient cells showed no difference in cell growth or morphology, and had normal downstream TXN activity while Nrf2 target gene transcripts were upregulated.

PMID 41116060 describes an additional individual with a severe metabolic disease; lactic acidosis, recurrent hypoglycaemia, significant developmental delay, epileptic seizures, and hypotonia. Homozygous for c.642_643insT p.(Ile215Tyrfs*59). Functional studies showed it disrupts SLC7A5-SLC3A2 endocytosis and cellular glucose uptake.
Sources: Literature
Fetal anomalies v1.469 ESRP2 Chirag Patel Classified gene: ESRP2 as Green List (high evidence)
Fetal anomalies v1.469 ESRP2 Chirag Patel Gene: esrp2 has been classified as Green List (High Evidence).
Mendeliome v1.3558 ESRP2 Chirag Patel Classified gene: ESRP2 as Green List (high evidence)
Mendeliome v1.3558 ESRP2 Chirag Patel Gene: esrp2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.76 ESRP2 Chirag Patel Classified gene: ESRP2 as Red List (low evidence)
Pituitary hormone deficiency v0.76 ESRP2 Chirag Patel Gene: esrp2 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.75 ESRP2 Chirag Patel Marked gene: ESRP2 as ready
Pituitary hormone deficiency v0.75 ESRP2 Chirag Patel Gene: esrp2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.75 ESRP2 Chirag Patel Phenotypes for gene: ESRP2 were changed from cleft lip; Cleft palate, MONDO:0016064; Hypopituitarism MONDO:0005152 to Cleft palate, MONDO:0016064; Hypopituitarism MONDO:0005152
Mendeliome v1.3557 Chirag Patel Added reviews for gene ESRP2 from panel Clefting disorders
Fetal anomalies v1.468 Chirag Patel Added reviews for gene ESRP2 from panel Clefting disorders
Pituitary hormone deficiency v0.74 Chirag Patel Copied gene ESRP2 from panel Clefting disorders
Pituitary hormone deficiency v0.74 ESRP2 Chirag Patel gene: ESRP2 was added
gene: ESRP2 was added to Pituitary hormone deficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ESRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ESRP2 were set to 29805042
Phenotypes for gene: ESRP2 were set to cleft lip; Cleft palate, MONDO:0016064; Hypopituitarism MONDO:0005152
Clefting disorders v0.281 ESRP2 Chirag Patel Phenotypes for gene: ESRP2 were changed from cleft lip to cleft lip; Cleft palate, MONDO:0016064; Hypopituitarism MONDO:0005152
Clefting disorders v0.280 ESRP2 Chirag Patel Classified gene: ESRP2 as Green List (high evidence)
Clefting disorders v0.280 ESRP2 Chirag Patel Gene: esrp2 has been classified as Green List (High Evidence).
Clefting disorders v0.279 ESRP2 Chirag Patel reviewed gene: ESRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41111330, 29180615, 33234718; Phenotypes: Cleft palate, MONDO:0016064, Hypopituitarism MONDO:0005152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.478 NAA16 Lucy Spencer Classified gene: NAA16 as Amber List (moderate evidence)
Congenital Heart Defect v0.478 NAA16 Lucy Spencer Gene: naa16 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3556 NAA16 Lucy Spencer Classified gene: NAA16 as Amber List (moderate evidence)
Mendeliome v1.3556 NAA16 Lucy Spencer Gene: naa16 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.477 Lucy Spencer Copied gene NAA16 from panel Mendeliome
Congenital Heart Defect v0.477 NAA16 Lucy Spencer gene: NAA16 was added
gene: NAA16 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: NAA16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA16 were set to 41148812; 23665959; 28991257
Phenotypes for gene: NAA16 were set to Congenital heart disease, MONDO:0005453, NAA16-related
Mendeliome v1.3555 NAA16 Lucy Spencer gene: NAA16 was added
gene: NAA16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAA16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA16 were set to 41148812; 23665959; 28991257
Phenotypes for gene: NAA16 were set to Congenital heart disease, MONDO:0005453, NAA16-related
Review for gene: NAA16 was set to AMBER
Added comment: NAA16 is part of the auxiliary subunit of the NatA complex along with NAA15. this complex is responsible for acetylating a broad range of proteins following initiator methionine removal. NAA15 and NAA10 which is part of the catalytic subunit of the complex have previously been associated with neurodevelopmental disorders, including CHD for NAA15.

PMID 41148812 3 individuals from 3 unrelated families with heterozygous NAA16 variants (p.R70C missense de novo; p.L765fs and p.E630fs frameshifts unclear inheritance) presenting with congenital heart disease (atrial septal defect, Tetralogy of Fallot, conotruncal defects). These 3 families were identified in a large cohort from the Paediatric Cardiac Genomic Consortium (PMID: 23665959, PMID: 28991257). One of the individuals with a frameshift is also listed as having a neurodevelopmental phenotype PMID: 28991257. Arg70Cys has 24 hets in gnomad and the gene is not very constrained for LOF.

PMID 41148812 Drosophila cardiac‑specific rescue assay shows loss‑of‑function for the missense variant (unable to rescue the phenotype), supporting pathogenicity.
Sources: Literature
Mendeliome v1.3554 NMNAT3 Chirag Patel Marked gene: NMNAT3 as ready
Mendeliome v1.3554 NMNAT3 Chirag Patel Gene: nmnat3 has been classified as Red List (Low Evidence).
Mendeliome v1.3554 Chirag Patel Copied gene NMNAT3 from panel Red cell disorders
Mendeliome v1.3554 NMNAT3 Chirag Patel gene: NMNAT3 was added
gene: NMNAT3 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NMNAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT3 were set to 41100733, 24739386
Phenotypes for gene: NMNAT3 were set to Familial hemolytic anemia, MONDO:0003689
Red cell disorders v1.36 NMNAT3 Chirag Patel Marked gene: NMNAT3 as ready
Red cell disorders v1.36 NMNAT3 Chirag Patel Gene: nmnat3 has been classified as Red List (Low Evidence).
Red cell disorders v1.36 NMNAT3 Chirag Patel gene: NMNAT3 was added
gene: NMNAT3 was added to Red cell disorders. Sources: Literature
Mode of inheritance for gene: NMNAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT3 were set to 41100733, 24739386
Phenotypes for gene: NMNAT3 were set to Familial hemolytic anemia, MONDO:0003689
Review for gene: NMNAT3 was set to RED
Added comment: NMNAT is an enzyme that plays a key role in the de novo biosynthesis and salvage of NAD+. Three isoforms of NMNAT exist in mammals (NMNAT1-3), and NMNAT3 is the predominant isoform in RBCs.

PMID:41100733
2 siblings from 1 consanguineous Turkish family with adolescent‑onset hereditary haemolytic anemia, splenomegaly and mild compensated haemolysis. Research based gene panel identified a homozygous variant in NMNAT3 gene (c.64C>T, (p.His22Tyr)) which is absent in gnomAD and located in the adenosine triphosphate (ATP) binding domain. Segregation showed mother was heterozygous and an unaffected sibling was wild-type.

Functional assays demonstrated absent NMNAT activity; decreased levels of NAD+, NADH, NAM, and NMN; and disturbed glycolysis. They noted partial hematologic improvement after NAD precursor supplementation. No contradictory evidence is reported.

PMID: 24739386
They showed that complete knockout of NMNAT3 in mice caused depletion of NAD+ and disturbed glycolytic flow in mature RBCs, resulting in haemolytic anemia and splenomegaly.
Sources: Literature
Mendeliome v1.3553 CASP1 Chirag Patel Marked gene: CASP1 as ready
Mendeliome v1.3553 CASP1 Chirag Patel Gene: casp1 has been classified as Red List (Low Evidence).
Mendeliome v1.3553 Chirag Patel Copied gene CASP1 from panel Defects of intrinsic and innate immunity
Mendeliome v1.3553 CASP1 Chirag Patel gene: CASP1 was added
gene: CASP1 was added to Mendeliome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP1 were set to 41101739
Phenotypes for gene: CASP1 were set to Absent IL18 and lymphopenia but no clinical disease
Defects of intrinsic and innate immunity v1.22 CASP1 Chirag Patel Marked gene: CASP1 as ready
Defects of intrinsic and innate immunity v1.22 CASP1 Chirag Patel Gene: casp1 has been classified as Red List (Low Evidence).
Defects of intrinsic and innate immunity v1.22 CASP1 Chirag Patel changed review comment from: 8 individuals from 2 consaguineous families (from Pakistani consanguineous biobank). Individuals had the same homozygous CASP1 variant (Tyr153Ter), suggesting founder variant. The adult individuals had markedly reduced IL‑18/IL‑1β secretion and low neutrophil counts but NO overt infection susceptibility. Functional assays in HEK293 cells, patient serum and PBMCs demonstrate complete loss of CASP1 activity. Caspase-1 (CASP1) is a key effector of the canonical inflammasome and innate immunity.
Sources: Literature; to: 8 adult individuals from 2 unrelated consaguineous families identified from Pakistani consanguineous biobank. Individuals had the same homozygous CASP1 variant (Tyr153Ter). The individuals had markedly reduced IL‑18/IL‑1β secretion and low neutrophil counts but NO overt infection susceptibility. Functional assays in HEK293 cells, patient serum and PBMCs demonstrate complete loss of CASP1 activity. Multiple heterozygote carriers in the families had reduced CASP1 protein and milder lymphopenia, but no clinical disease. Caspase-1 (CASP1) is a key effector of the canonical inflammasome and innate immunity.
Sources: Literature
Defects of intrinsic and innate immunity v1.22 CASP1 Chirag Patel gene: CASP1 was added
gene: CASP1 was added to Defects of intrinsic and innate immunity. Sources: Literature
Mode of inheritance for gene: CASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP1 were set to 41101739
Phenotypes for gene: CASP1 were set to Absent IL18 and lymphopenia but no clinical disease
Review for gene: CASP1 was set to RED
Added comment: 8 individuals from 2 consaguineous families (from Pakistani consanguineous biobank). Individuals had the same homozygous CASP1 variant (Tyr153Ter), suggesting founder variant. The adult individuals had markedly reduced IL‑18/IL‑1β secretion and low neutrophil counts but NO overt infection susceptibility. Functional assays in HEK293 cells, patient serum and PBMCs demonstrate complete loss of CASP1 activity. Caspase-1 (CASP1) is a key effector of the canonical inflammasome and innate immunity.
Sources: Literature
Deafness_IsolatedAndComplex v1.290 COL4A3 Chirag Patel Mode of inheritance for gene: COL4A3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.289 COL4A3 Chirag Patel edited their review of gene: COL4A3: Added comment: ARAS - 50%-60% typically exhibit hearing loss
ADAS - hearing loss is usually a very late development; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.289 COL4A4 Chirag Patel Phenotypes for gene: COL4A4 were changed from Alport syndrome 2, autosomal recessive MIM#203780; Hematuria, familial benign MIM#141200 to Alport syndrome 2, autosomal recessive, MIM# 203780; Alport syndrome 3, autosomal dominant, MIM# 104200
Deafness_IsolatedAndComplex v1.288 COL4A3 Chirag Patel Deleted their comment
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel Marked gene: COL4A4 as ready
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel Gene: col4a4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.288 COL4A3 Chirag Patel Marked gene: COL4A3 as ready
Deafness_IsolatedAndComplex v1.288 COL4A3 Chirag Patel Gene: col4a3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.288 COL4A3 Chirag Patel commented on gene: COL4A3
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel edited their review of gene: COL4A4: Added comment: ARAS - 50%-60% typically exhibit hearing loss
ADAS - hearing loss is usually a very late development; Changed rating: GREEN; Changed phenotypes: Alport syndrome 2, autosomal recessive, MIM# 203780, Alport syndrome 3, autosomal dominant, MIM# 104200; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel Deleted their comment
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel commented on gene: COL4A4
Mendeliome v1.3552 NOL10 Sangavi Sivagnanasundram gene: NOL10 was added
gene: NOL10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOL10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOL10 were set to 41093997
Phenotypes for gene: NOL10 were set to NOL10-related neurological disorder MONDO:0100545
Review for gene: NOL10 was set to RED
Added comment: 12yr F with recurrent focal seizures, progressive memory impairment and atrophy and parietal gliosis on MRI. Homozygous missense variant was identified (NM_024894.4: c.682 A > C; p.Asn228His). The variant is absent in gnomAD v4.1

Functional study using patient-derived fibroblasts was conducted and showed defective ribosome biogenesis. As this is a new gene disease association, it is unclear if that is the mechanism of disease. Need more evidence to promote the gene to Amber.
Sources: Literature
Deafness_IsolatedAndComplex v1.288 Chirag Patel Copied gene COL4A3 from panel Mendeliome
Deafness_IsolatedAndComplex v1.288 COL4A3 Chirag Patel gene: COL4A3 was added
gene: COL4A3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL4A3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: COL4A3 were set to Alport syndrome 2, autosomal recessive, MIM# 203780; Alport syndrome 3, autosomal dominant, MIM# 104200
Deafness_IsolatedAndComplex v1.288 Chirag Patel Copied gene COL4A4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.288 COL4A4 Chirag Patel gene: COL4A4 was added
gene: COL4A4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL4A4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: COL4A4 were set to 20301386
Phenotypes for gene: COL4A4 were set to Alport syndrome 2, autosomal recessive MIM#203780; Hematuria, familial benign MIM#141200
Deafness_IsolatedAndComplex v1.287 ERCC4 Chirag Patel Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, MIM# 278760; MONDO:0010215 to Xeroderma pigmentosum, group F, MIM# 278760; MONDO:0010215
Deafness_IsolatedAndComplex v1.287 ERCC4 Chirag Patel Phenotypes for gene: ERCC4 were changed from Fanconi anemia, complementation group Q, MIM# 615272; MONDO:0014108; Xeroderma pigmentosum, group F, MIM# 278760; MONDO:0010215; XFE progeroid syndrome, MIM# 610965; MONDO:0012590 to Xeroderma pigmentosum, group F, MIM# 278760; MONDO:0010215
Deafness_IsolatedAndComplex v1.286 ERCC4 Chirag Patel Marked gene: ERCC4 as ready
Deafness_IsolatedAndComplex v1.286 ERCC4 Chirag Patel Gene: ercc4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.286 ERCC4 Chirag Patel reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group F, MIM# 278760, MONDO:0010215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.286 Chirag Patel Copied gene ERCC4 from panel Mendeliome
Deafness_IsolatedAndComplex v1.286 ERCC4 Chirag Patel gene: ERCC4 was added
gene: ERCC4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC4 were set to 23623386; 8797827; 23623389; 17183314; 29105242
Phenotypes for gene: ERCC4 were set to Fanconi anemia, complementation group Q, MIM# 615272; MONDO:0014108; Xeroderma pigmentosum, group F, MIM# 278760; MONDO:0010215; XFE progeroid syndrome, MIM# 610965; MONDO:0012590
Deafness_IsolatedAndComplex v1.286 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.285 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.284 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.284 ERCC3 Chirag Patel Phenotypes for gene: ERCC3 were changed from Trichothiodystrophy 2, photosensitive, MIM# 616390; Xeroderma pigmentosum, group B 61, MIM#0651 to Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.283 ERCC3 Chirag Patel Marked gene: ERCC3 as ready
Deafness_IsolatedAndComplex v1.283 ERCC3 Chirag Patel Gene: ercc3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.283 ERCC3 Chirag Patel reviewed gene: ERCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group B 61, MIM#0651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.283 ERCC2 Chirag Patel Phenotypes for gene: ERCC2 were changed from Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212 to Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212
Deafness_IsolatedAndComplex v1.282 ERCC2 Chirag Patel Phenotypes for gene: ERCC2 were changed from Cerebrooculofacioskeletal syndrome 2, MIM# 610756; MONDO:0012553; Trichothiodystrophy 1, photosensitive, MIM# 601675; MONDO:0011125; Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212 to Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212
Deafness_IsolatedAndComplex v1.281 ERCC2 Chirag Patel Marked gene: ERCC2 as ready
Deafness_IsolatedAndComplex v1.281 ERCC2 Chirag Patel Gene: ercc2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.281 ERCC2 Chirag Patel reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group D, MIM# 278730, MONDO:0010212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.281 XPA Chirag Patel Marked gene: XPA as ready
Deafness_IsolatedAndComplex v1.281 XPA Chirag Patel Gene: xpa has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.281 XPA Chirag Patel commented on gene: XPA
Deafness_IsolatedAndComplex v1.281 Chirag Patel Copied gene ERCC3 from panel Mendeliome
Deafness_IsolatedAndComplex v1.281 ERCC3 Chirag Patel gene: ERCC3 was added
gene: ERCC3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC3 were set to 2167179; 10447254; 16947863; 9012405; 32557569; 27004399
Phenotypes for gene: ERCC3 were set to Trichothiodystrophy 2, photosensitive, MIM# 616390; Xeroderma pigmentosum, group B 61, MIM#0651
Deafness_IsolatedAndComplex v1.281 Chirag Patel Copied gene ERCC2 from panel Mendeliome
Deafness_IsolatedAndComplex v1.281 ERCC2 Chirag Patel gene: ERCC2 was added
gene: ERCC2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC2 were set to 7849702; 9758621; 11443545; 33733458
Phenotypes for gene: ERCC2 were set to Cerebrooculofacioskeletal syndrome 2, MIM# 610756; MONDO:0012553; Trichothiodystrophy 1, photosensitive, MIM# 601675; MONDO:0011125; Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212
Deafness_IsolatedAndComplex v1.280 Chirag Patel Copied gene XPA from panel Mendeliome
Deafness_IsolatedAndComplex v1.280 XPA Chirag Patel gene: XPA was added
gene: XPA was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: XPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPA were set to 2234061; 1372102
Phenotypes for gene: XPA were set to Xeroderma pigmentosum, group A , MIM#278700; MONDO:0010210
Deafness_IsolatedAndComplex v1.279 PTRH2 Chirag Patel Marked gene: PTRH2 as ready
Deafness_IsolatedAndComplex v1.279 PTRH2 Chirag Patel Gene: ptrh2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.279 Chirag Patel Copied gene PTRH2 from panel Mendeliome
Deafness_IsolatedAndComplex v1.279 PTRH2 Chirag Patel gene: PTRH2 was added
gene: PTRH2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRH2 were set to 25558065; 25574476; 31057140; 27129381
Phenotypes for gene: PTRH2 were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, MIM# 616263
Deafness_IsolatedAndComplex v1.278 PLCG1 Chirag Patel Marked gene: PLCG1 as ready
Deafness_IsolatedAndComplex v1.278 PLCG1 Chirag Patel Gene: plcg1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.278 Chirag Patel Copied gene PLCG1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.278 PLCG1 Chirag Patel gene: PLCG1 was added
gene: PLCG1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: PLCG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLCG1 were set to 37422272; 40862571
Phenotypes for gene: PLCG1 were set to Immune dysregulation, autoimmunity, and autoinflammation, MIM# 620514
Mode of pathogenicity for gene: PLCG1 was set to Other
Deafness_IsolatedAndComplex v1.277 COG4 Chirag Patel Marked gene: COG4 as ready
Deafness_IsolatedAndComplex v1.277 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.277 COG4 Chirag Patel reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30290151; Phenotypes: Saul-Wilson syndrome, OMIM:618150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.277 Chirag Patel Copied gene COG4 from panel Growth failure
Deafness_IsolatedAndComplex v1.277 COG4 Chirag Patel gene: COG4 was added
gene: COG4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: COG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COG4 were set to 30290151; 31949312
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM:618150; Microcephalic osteodysplastic dysplasia, Saul-Wilson type, MONDO:0019407
Mode of pathogenicity for gene: COG4 was set to Other
Deafness_IsolatedAndComplex v1.276 ARSG Chirag Patel Marked gene: ARSG as ready
Deafness_IsolatedAndComplex v1.276 ARSG Chirag Patel Gene: arsg has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.276 ARSG Chirag Patel reviewed gene: ARSG: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300381, 32455177, 33300174, 33629623, 35226187; Phenotypes: Usher syndrome, type 4, MONDO:0029141; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.276 Chirag Patel Copied gene ARSG from panel Usher Syndrome
Deafness_IsolatedAndComplex v1.276 ARSG Chirag Patel gene: ARSG was added
gene: ARSG was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ARSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSG were set to 29300381; 20679209; 25452429; 26975023; 33300174; 32455177
Phenotypes for gene: ARSG were set to Usher syndrome, type IV, 618144
Deafness_IsolatedAndComplex v1.275 NLRP12 Chirag Patel reviewed gene: NLRP12: Rating: AMBER; Mode of pathogenicity: None; Publications: 18230725, 24064030, 31820221; Phenotypes: Familial cold autoinflammatory syndrome 2, OMIM:611762; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.275 NLRP12 Chirag Patel Classified gene: NLRP12 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.275 NLRP12 Chirag Patel Gene: nlrp12 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.274 NLRP12 Chirag Patel Marked gene: NLRP12 as ready
Deafness_IsolatedAndComplex v1.274 NLRP12 Chirag Patel Gene: nlrp12 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.274 Chirag Patel Copied gene NLRP12 from panel Mendeliome
Deafness_IsolatedAndComplex v1.274 NLRP12 Chirag Patel gene: NLRP12 was added
gene: NLRP12 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP12 were set to 18230725; 21360512; 24064030; 27633793; 38343435
Phenotypes for gene: NLRP12 were set to Familial cold autoinflammatory syndrome 2 - MIM#611762
Deafness_IsolatedAndComplex v1.273 DNAJC3 Chirag Patel Marked gene: DNAJC3 as ready
Deafness_IsolatedAndComplex v1.273 DNAJC3 Chirag Patel Gene: dnajc3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.273 DNAJC3 Chirag Patel Publications for gene: DNAJC3 were set to 33486469; 34630333; 34654017; 32738013
Deafness_IsolatedAndComplex v1.272 DNAJC3 Chirag Patel reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466870, 28940199, 32738013, 33486469, 34654017; Phenotypes: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.272 Chirag Patel Copied gene DNAJC3 from panel Mendeliome
Deafness_IsolatedAndComplex v1.272 DNAJC3 Chirag Patel gene: DNAJC3 was added
gene: DNAJC3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 33486469; 34630333; 34654017; 32738013
Phenotypes for gene: DNAJC3 were set to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus - MIM#616192
Palmoplantar Keratoderma and Erythrokeratoderma v0.137 AP1B1 Chirag Patel Marked gene: AP1B1 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.137 AP1B1 Chirag Patel Gene: ap1b1 has been classified as Green List (High Evidence).
Congenital Diarrhoea v1.29 AP1B1 Chirag Patel Marked gene: AP1B1 as ready
Congenital Diarrhoea v1.29 AP1B1 Chirag Patel Gene: ap1b1 has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.137 Chirag Patel Copied gene AP1B1 from panel Mendeliome
Palmoplantar Keratoderma and Erythrokeratoderma v0.137 AP1B1 Chirag Patel gene: AP1B1 was added
gene: AP1B1 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Expert Review Green,Literature
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855
Phenotypes for gene: AP1B1 were set to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Intellectual disability syndromic and non-syndromic v1.419 Chirag Patel Added reviews for gene AP1B1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.271 Chirag Patel Added reviews for gene AP1B1 from panel Mendeliome
Congenital Diarrhoea v1.29 Chirag Patel Copied gene AP1B1 from panel Mendeliome
Congenital Diarrhoea v1.29 AP1B1 Chirag Patel gene: AP1B1 was added
gene: AP1B1 was added to Congenital Diarrhoea. Sources: Expert Review Green,Literature
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855
Phenotypes for gene: AP1B1 were set to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Mendeliome v1.3551 AP1B1 Chirag Patel Phenotypes for gene: AP1B1 were changed from Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440 to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Mendeliome v1.3551 AP1B1 Chirag Patel Phenotypes for gene: AP1B1 were changed from Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150 to Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440
Mendeliome v1.3550 AP1B1 Chirag Patel Publications for gene: AP1B1 were set to 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855
Mendeliome v1.3550 AP1B1 Chirag Patel Publications for gene: AP1B1 were set to 31630788; 31630791
Mendeliome v1.3549 AP1B1 Chirag Patel reviewed gene: AP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31630791, 31630788, 33452671, 33349978, 35144013, 37657632, 32969855; Phenotypes: Ichthyosiform erythroderma, corneal involvement, and hearing loss MONDO:0009440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.270 AP1S1 Chirag Patel Phenotypes for gene: AP1S1 were changed from MEDNIK syndrome, MONDO:0012251 to MEDNIK syndrome, MONDO:0012251
Congenital Diarrhoea v1.28 AP1S1 Chirag Patel Phenotypes for gene: AP1S1 were changed from Non-syndromic congenital intestinal failure to MEDNIK syndrome, MONDO:0012251
Congenital Diarrhoea v1.28 AP1S1 Chirag Patel Publications for gene: AP1S1 were set to PMID: 32306098
Deafness_IsolatedAndComplex v1.269 AP1S1 Chirag Patel Phenotypes for gene: AP1S1 were changed from MEDNIK syndrome 609313; non-syndromic congenital intestinal failure to MEDNIK syndrome, MONDO:0012251
Congenital Diarrhoea v1.27 AP1S1 Chirag Patel Classified gene: AP1S1 as Green List (high evidence)
Congenital Diarrhoea v1.27 AP1S1 Chirag Patel Gene: ap1s1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.269 AP1S1 Chirag Patel Publications for gene: AP1S1 were set to 32306098
Deafness_IsolatedAndComplex v1.268 AP1S1 Chirag Patel Marked gene: AP1S1 as ready
Deafness_IsolatedAndComplex v1.268 AP1S1 Chirag Patel Gene: ap1s1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.268 Chirag Patel Copied gene AP1S1 from panel Mendeliome
Deafness_IsolatedAndComplex v1.268 AP1S1 Chirag Patel gene: AP1S1 was added
gene: AP1S1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to 32306098
Phenotypes for gene: AP1S1 were set to MEDNIK syndrome 609313; non-syndromic congenital intestinal failure
Congenital Diarrhoea v1.26 Chirag Patel Added reviews for gene AP1S1 from panel Mendeliome
Mendeliome v1.3549 AP1S1 Chirag Patel reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19057675, 23423674, 30244301, 32306098, 24754424, 39541497; Phenotypes: MEDNIK syndrome, MONDO:0012251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.267 TUBB4B Chirag Patel Publications for gene: TUBB4B were set to 31884617, 38662826, 37448631, 35240325, 38719929, 39876836, 29198720
Deafness_IsolatedAndComplex v1.267 TUBB4B Chirag Patel Publications for gene: TUBB4B were set to 31884617, 38662826, 37448631, 35240325, 38719929, 39876836, 29198720
Deafness_IsolatedAndComplex v1.266 TUBB4B Chirag Patel Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness, MIM# 617879 to TUBB4B-related ciliopathy, MONDO:1060115
Deafness_IsolatedAndComplex v1.266 TUBB4B Chirag Patel Publications for gene: TUBB4B were set to 29198720
Deafness_IsolatedAndComplex v1.265 TUBB4B Chirag Patel edited their review of gene: TUBB4B: Added comment: ClinGen definitive gene-disease association.
Affected individuals also exhibited congenital or childhood onset sensorineural hearing impairment.; Changed publications: 31884617, 38662826, 37448631, 35240325, 38719929, 39876836, 29198720; Changed phenotypes: TUBB4B-related ciliopathy, MONDO:1060115
Deafness_IsolatedAndComplex v1.265 TRPV4 Chirag Patel Phenotypes for gene: TRPV4 were changed from Auditory neuropathy spectrum disorder; Peripheral neuropathy; Hearing loss to Auditory neuropathy spectrum disorder; Charcot-Marie-Tooth disease axonal type 2C, MONDO:0011633; Hearing loss
Deafness_IsolatedAndComplex v1.264 TRPV4 Chirag Patel reviewed gene: TRPV4: Rating: GREEN; Mode of pathogenicity: None; Publications: 20037586; Phenotypes: Charcot-Marie-Tooth disease axonal type 2C, MONDO:0011633; Mode of inheritance: None
Deafness_IsolatedAndComplex v1.264 TMEM132E Chirag Patel Classified gene: TMEM132E as Red List (low evidence)
Deafness_IsolatedAndComplex v1.264 TMEM132E Chirag Patel Gene: tmem132e has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.263 PSMC3 Chirag Patel Classified gene: PSMC3 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.263 PSMC3 Chirag Patel Gene: psmc3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.262 PSMC3 Chirag Patel reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37256937; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.262 PAX2 Chirag Patel Classified gene: PAX2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.262 PAX2 Chirag Patel Gene: pax2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.261 PAX2 Chirag Patel reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22213154; Phenotypes: Renal coloboma syndrome, MONDO:0007352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.261 DSPP Chirag Patel Classified gene: DSPP as Green List (high evidence)
Deafness_IsolatedAndComplex v1.261 DSPP Chirag Patel Gene: dspp has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 DSPP Chirag Patel reviewed gene: DSPP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11175790, 15690376, 17686168, 15592686, 18456718, 15241678; Phenotypes: Dentinogenesis imperfecta, MONDO:0018849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.260 ADAMTS1 Chirag Patel Marked gene: ADAMTS1 as ready
Deafness_IsolatedAndComplex v1.260 ADAMTS1 Chirag Patel Gene: adamts1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 ANKRD24 Chirag Patel Marked gene: ANKRD24 as ready
Deafness_IsolatedAndComplex v1.260 ANKRD24 Chirag Patel Gene: ankrd24 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 ATP11A Chirag Patel Marked gene: ATP11A as ready
Deafness_IsolatedAndComplex v1.260 ATP11A Chirag Patel Gene: atp11a has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 CPD Chirag Patel Marked gene: CPD as ready
Deafness_IsolatedAndComplex v1.260 CPD Chirag Patel Gene: cpd has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 GOSR2 Chirag Patel Marked gene: GOSR2 as ready
Deafness_IsolatedAndComplex v1.260 GOSR2 Chirag Patel Gene: gosr2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 IKZF2 Chirag Patel Marked gene: IKZF2 as ready
Deafness_IsolatedAndComplex v1.260 IKZF2 Chirag Patel Gene: ikzf2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 MEPE Chirag Patel Marked gene: MEPE as ready
Deafness_IsolatedAndComplex v1.260 MEPE Chirag Patel Gene: mepe has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.260 MPDZ Chirag Patel Marked gene: MPDZ as ready
Deafness_IsolatedAndComplex v1.260 MPDZ Chirag Patel Gene: mpdz has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 NCOA3 Chirag Patel Marked gene: NCOA3 as ready
Deafness_IsolatedAndComplex v1.260 NCOA3 Chirag Patel Gene: ncoa3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 REST Chirag Patel Marked gene: REST as ready
Deafness_IsolatedAndComplex v1.260 REST Chirag Patel Gene: rest has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.260 SEZ6 Chirag Patel Marked gene: SEZ6 as ready
Deafness_IsolatedAndComplex v1.260 SEZ6 Chirag Patel Gene: sez6 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 SMARCA4 Chirag Patel Marked gene: SMARCA4 as ready
Deafness_IsolatedAndComplex v1.260 SMARCA4 Chirag Patel Gene: smarca4 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 TECTB Chirag Patel Marked gene: TECTB as ready
Deafness_IsolatedAndComplex v1.260 TECTB Chirag Patel Gene: tectb has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 TRRAP Chirag Patel Marked gene: TRRAP as ready
Deafness_IsolatedAndComplex v1.260 TRRAP Chirag Patel Gene: trrap has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 CENPP Chirag Patel Marked gene: CENPP as ready
Deafness_IsolatedAndComplex v1.260 CENPP Chirag Patel Gene: cenpp has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 MAP3K1 Chirag Patel Marked gene: MAP3K1 as ready
Deafness_IsolatedAndComplex v1.260 MAP3K1 Chirag Patel Gene: map3k1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 TOGARAM2 Chirag Patel Marked gene: TOGARAM2 as ready
Deafness_IsolatedAndComplex v1.260 TOGARAM2 Chirag Patel Gene: togaram2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 STX4 Chirag Patel Marked gene: STX4 as ready
Deafness_IsolatedAndComplex v1.260 STX4 Chirag Patel Gene: stx4 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.260 MVD Chirag Patel Marked gene: MVD as ready
Deafness_IsolatedAndComplex v1.260 MVD Chirag Patel Gene: mvd has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 PKHD1L1 Chirag Patel Marked gene: PKHD1L1 as ready
Deafness_IsolatedAndComplex v1.260 PKHD1L1 Chirag Patel Gene: pkhd1l1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 FXN Chirag Patel Marked gene: FXN as ready
Deafness_IsolatedAndComplex v1.260 FXN Chirag Patel Gene: fxn has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 MPZ Chirag Patel Marked gene: MPZ as ready
Deafness_IsolatedAndComplex v1.260 MPZ Chirag Patel Gene: mpz has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 PCDH9 Chirag Patel Marked gene: PCDH9 as ready
Deafness_IsolatedAndComplex v1.260 PCDH9 Chirag Patel Gene: pcdh9 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.260 TMEM126A Chirag Patel Marked gene: TMEM126A as ready
Deafness_IsolatedAndComplex v1.260 TMEM126A Chirag Patel Gene: tmem126a has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.260 NEFL Chirag Patel Marked gene: NEFL as ready
Deafness_IsolatedAndComplex v1.260 NEFL Chirag Patel Gene: nefl has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.260 Chirag Patel HPO terms changed from Hearing impairment, HP:0000365 to Hearing impairment, HP:0000365; Sensorineural hearing impairment HP:0000407
Deafness_IsolatedAndComplex v1.259 Chirag Patel Copied gene NEFL from panel Auditory Neuropathy
Deafness_IsolatedAndComplex v1.259 NEFL Chirag Patel gene: NEFL was added
gene: NEFL was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NEFL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEFL were set to 21176974
Phenotypes for gene: NEFL were set to Syndromic auditory neuropathy spectrum disorder
Deafness_IsolatedAndComplex v1.258 Chirag Patel Copied gene TMEM126A from panel Auditory Neuropathy
Deafness_IsolatedAndComplex v1.258 TMEM126A Chirag Patel gene: TMEM126A was added
gene: TMEM126A was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TMEM126A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM126A were set to 21176974
Phenotypes for gene: TMEM126A were set to Optic atrophy 7 MIM#612989; Syndromic auditory neuropathy spectrum disorder
Deafness_IsolatedAndComplex v1.257 PMP22 Chirag Patel Classified gene: PMP22 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.257 PMP22 Chirag Patel Gene: pmp22 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.257 PMP22 Chirag Patel Classified gene: PMP22 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.257 PMP22 Chirag Patel Gene: pmp22 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.256 Chirag Patel Copied gene PCDH9 from panel Auditory Neuropathy
Deafness_IsolatedAndComplex v1.256 PCDH9 Chirag Patel gene: PCDH9 was added
gene: PCDH9 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PCDH9 was set to Unknown
Publications for gene: PCDH9 were set to 21176974
Phenotypes for gene: PCDH9 were set to Non-syndromic auditory neuropathy spectrum disorder
Deafness_IsolatedAndComplex v1.255 Chirag Patel Copied gene MPZ from panel Auditory Neuropathy
Deafness_IsolatedAndComplex v1.255 MPZ Chirag Patel gene: MPZ was added
gene: MPZ was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MPZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MPZ were set to 21176974; 12845552; 12805115
Phenotypes for gene: MPZ were set to Syndromic auditory neuropathy spectrum disorder
Deafness_IsolatedAndComplex v1.255 Chirag Patel Copied gene FXN from panel Auditory Neuropathy
Deafness_IsolatedAndComplex v1.255 FXN Chirag Patel gene: FXN was added
gene: FXN was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
STR tags were added to gene: FXN.
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXN were set to 18515321; 25791504
Phenotypes for gene: FXN were set to Friedreich ataxia MIM#229300
Deafness_IsolatedAndComplex v1.254 Chirag Patel Copied gene PKHD1L1 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.254 PKHD1L1 Chirag Patel gene: PKHD1L1 was added
gene: PKHD1L1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PKHD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKHD1L1 were set to 38459354
Phenotypes for gene: PKHD1L1 were set to non syndromic hearing loss (MONDO:0020678)
Deafness_IsolatedAndComplex v1.253 Chirag Patel Copied gene MVD from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.253 MVD Chirag Patel gene: MVD was added
gene: MVD was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MVD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVD were set to 34135477
Phenotypes for gene: MVD were set to Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related
Deafness_IsolatedAndComplex v1.252 Chirag Patel Copied gene STX4 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.252 STX4 Chirag Patel gene: STX4 was added
gene: STX4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: STX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX4 were set to 36355422
Phenotypes for gene: STX4 were set to Deafness, autosomal recessive 123, MIM# 620745
Deafness_IsolatedAndComplex v1.252 Chirag Patel Copied gene TOGARAM2 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.252 TOGARAM2 Chirag Patel gene: TOGARAM2 was added
gene: TOGARAM2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Deafness_IsolatedAndComplex v1.251 Chirag Patel Copied gene MAP3K1 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.251 MAP3K1 Chirag Patel gene: MAP3K1 was added
gene: MAP3K1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MAP3K1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAP3K1 were set to 39062623
Phenotypes for gene: MAP3K1 were set to Hearing loss disorder, MONDO:0005365, MAP3K1-related
Deafness_IsolatedAndComplex v1.250 Chirag Patel Copied gene CENPP from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.250 CENPP Chirag Patel gene: CENPP was added
gene: CENPP was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: CENPP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CENPP were set to 36071244
Phenotypes for gene: CENPP were set to autosomal dominant nonsyndromic hearing loss; MONDO:0019587
Deafness_IsolatedAndComplex v1.249 Chirag Patel Copied gene TRRAP from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.249 TRRAP Chirag Patel gene: TRRAP was added
gene: TRRAP was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRRAP were set to PMID: 31231791
Phenotypes for gene: TRRAP were set to Deafness, autosomal dominant 75 MIM#618778
Deafness_IsolatedAndComplex v1.248 Chirag Patel Copied gene TECTB from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.248 TECTB Chirag Patel gene: TECTB was added
gene: TECTB was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: TECTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TECTB were set to 40832383
Phenotypes for gene: TECTB were set to Hearing loss disorder, MONDO:0005365, TECTB-related
Deafness_IsolatedAndComplex v1.248 Chirag Patel Copied gene SMARCA4 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.248 SMARCA4 Chirag Patel gene: SMARCA4 was added
gene: SMARCA4 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCA4 were set to 37399313
Phenotypes for gene: SMARCA4 were set to Otosclerosis MONDO:0005349, SMARCA4-related
Deafness_IsolatedAndComplex v1.247 Chirag Patel Copied gene SEZ6 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.247 SEZ6 Chirag Patel gene: SEZ6 was added
gene: SEZ6 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: SEZ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEZ6 were set to 34135477
Phenotypes for gene: SEZ6 were set to Nonsyndromic genetic hearing loss MONDO:0019497, SEZ6-related
Deafness_IsolatedAndComplex v1.247 Chirag Patel Copied gene REST from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.247 REST Chirag Patel gene: REST was added
gene: REST was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 29961578; 34828371
Phenotypes for gene: REST were set to Deafness, autosomal dominant 27, MIM# 612431
Deafness_IsolatedAndComplex v1.246 Chirag Patel Copied gene NCOA3 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.246 NCOA3 Chirag Patel gene: NCOA3 was added
gene: NCOA3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: NCOA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NCOA3 were set to 33326993
Phenotypes for gene: NCOA3 were set to Non-syndromic hearing loss
Deafness_IsolatedAndComplex v1.245 Chirag Patel Copied gene MPDZ from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.245 MPDZ Chirag Patel gene: MPDZ was added
gene: MPDZ was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MPDZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPDZ were set to 34135477; 29026089
Phenotypes for gene: MPDZ were set to Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related
Deafness_IsolatedAndComplex v1.245 Chirag Patel Copied gene MEPE from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.245 MEPE Chirag Patel gene: MEPE was added
gene: MEPE was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to Nonsyndromic genetic hearing loss, MONDO:0019497, MEPE-related; hereditary congenital facial paresis; otosclerosis
Deafness_IsolatedAndComplex v1.244 Chirag Patel Copied gene IKZF2 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.244 IKZF2 Chirag Patel gene: IKZF2 was added
gene: IKZF2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: IKZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF2 were set to PMID: 39406892
Phenotypes for gene: IKZF2 were set to nonsyndromic genetic hearing loss MONDO:0019497, IKZF2-related
Deafness_IsolatedAndComplex v1.244 Chirag Patel Copied gene GOSR2 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.244 GOSR2 Chirag Patel gene: GOSR2 was added
gene: GOSR2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Expert Review
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to 37074134
Phenotypes for gene: GOSR2 were set to hearing loss, autosomal recessive, MONDO:0019588, GOSR2-related
Deafness_IsolatedAndComplex v1.243 Chirag Patel Copied gene CPD from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.243 CPD Chirag Patel gene: CPD was added
gene: CPD was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPD were set to PMID: 41026541
Phenotypes for gene: CPD were set to Nonsyndromic genetic hearing loss, MONDO:0019497, CPD-related
Deafness_IsolatedAndComplex v1.242 Chirag Patel Copied gene ATP11A from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.242 ATP11A Chirag Patel gene: ATP11A was added
gene: ATP11A was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 35278131; 36300302
Phenotypes for gene: ATP11A were set to Deafness, autosomal dominant 84, MIM# 619810; Auditory neuropathy, autosomal dominant 2, MIM# 620384
Deafness_IsolatedAndComplex v1.242 Chirag Patel Copied gene ANKRD24 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.242 ANKRD24 Chirag Patel gene: ANKRD24 was added
gene: ANKRD24 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ANKRD24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANKRD24 were set to PMID: 39434538
Phenotypes for gene: ANKRD24 were set to sensorineural hearing loss disorder MONDO:0020678, ANKRD24-related
Deafness_IsolatedAndComplex v1.241 Chirag Patel Copied gene ADAMTS1 from panel Deafness_Isolated
Deafness_IsolatedAndComplex v1.241 ADAMTS1 Chirag Patel gene: ADAMTS1 was added
gene: ADAMTS1 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS1 were set to 34135477
Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related
Autoinflammatory Disorders v2.29 Sarah Milton Copied gene QSER1 from panel Fetal anomalies
Autoinflammatory Disorders v2.29 QSER1 Sarah Milton gene: QSER1 was added
gene: QSER1 was added to Autoinflammatory Disorders. Sources: Expert Review Red,Literature,Literature
Mode of inheritance for gene: QSER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: QSER1 were set to PMID: 41139957
Phenotypes for gene: QSER1 were set to Neurodevelopmental disorder, MONDO:0700092, QSER1-related
Mendeliome v1.3549 ZNF334 Sarah Milton gene: ZNF334 was added
gene: ZNF334 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF334 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF334 were set to PIMD: 41168503
Phenotypes for gene: ZNF334 were set to Familial cold autoinflammatory syndrome, MONDO:0018768, ZNF334-related
Review for gene: ZNF334 was set to RED
Added comment: ZNF334 encodes zinc finger protein 334 and function is not clearly defined.

PMID: 41168503 describes 1 individual with late onset cold induced autoinflammatory disease (urticaria, fever, arthralgia, lymphadenopathy, onset 40 yo) and progressive SNHL.

Functional studies indicated reduced interaction ZNF334 and HSP90 (a cold stress regulator protein), monocytic cells lines with truncated ZNF344 showed enhanced cold induced TNF/NFKB1/NLRP3/STAT3 signalling.

This variant was truncating NMD escape, however the gene has pLI = 0.
Further literature is required.
Sources: Literature
Arthrogryposis v0.466 ADAMTS10 Zornitza Stark Mode of inheritance for gene: ADAMTS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.465 ADAMTS10 Zornitza Stark changed review comment from: Comment when marking as ready: Joint stiffness and limitations described as part of the phenotype.; to: Joint stiffness and limitations described as part of the phenotype.
Arthrogryposis v0.465 ADAMTS10 Zornitza Stark Deleted their comment
Arthrogryposis v0.465 DOK7 Zornitza Stark Marked gene: DOK7 as ready
Arthrogryposis v0.465 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Arthrogryposis v0.465 DOK7 Zornitza Stark Phenotypes for gene: DOK7 were changed from to Fetal akinesia deformation sequence 3, MIM# 618389; Myasthenic syndrome, congenital, 10, MIM# 254300
Arthrogryposis v0.464 DOK7 Zornitza Stark Publications for gene: DOK7 were set to
Arthrogryposis v0.463 DOK7 Zornitza Stark Mode of inheritance for gene: DOK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.462 DOK7 Zornitza Stark edited their review of gene: DOK7: Changed phenotypes: Fetal akinesia deformation sequence 3, MIM# 618389, Myasthenic syndrome, congenital, 10, MIM# 254300
Arthrogryposis v0.462 Zornitza Stark Added reviews for gene DOK7 from panel Multiple pterygium syndrome_Fetal akinesia sequence
Arthrogryposis v0.461 COLQ Zornitza Stark Marked gene: COLQ as ready
Arthrogryposis v0.461 COLQ Zornitza Stark Gene: colq has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.461 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from to Myasthenic syndrome, congenital, 5, MIM# 603034
Arthrogryposis v0.460 COLQ Zornitza Stark Publications for gene: COLQ were set to
Arthrogryposis v0.459 COLQ Zornitza Stark Mode of inheritance for gene: COLQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.458 COLQ Zornitza Stark Classified gene: COLQ as Amber List (moderate evidence)
Arthrogryposis v0.458 COLQ Zornitza Stark Gene: colq has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.457 COLQ Zornitza Stark changed review comment from: Well established gene-disease association, more than 10 families reported. However, cannot find reports of presentation with multiple pterygia specifically.; to: Well established gene-disease association, more than 10 families reported. However, cannot find reports of presentation with arthrogryposis specifically, though contractures are common in the Congenital Myasthenic Syndromes, hence Amber rating.
Arthrogryposis v0.457 Zornitza Stark Added reviews for gene COLQ from panel Multiple pterygium syndrome_Fetal akinesia sequence
Arthrogryposis v0.456 CHRND Zornitza Stark Marked gene: CHRND as ready
Arthrogryposis v0.456 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Arthrogryposis v0.456 CHRND Zornitza Stark Phenotypes for gene: CHRND were changed from to Multiple pterygium syndrome, lethal type, MIM# 253290
Arthrogryposis v0.455 CHRND Zornitza Stark Mode of inheritance for gene: CHRND was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.454 CHRND Zornitza Stark changed review comment from: Typically presents with cystic hygroma/hydrops fetalis.; to: Typically presents with cystic hygroma/hydrops fetalis. Arthrogryposis is a feature.
Arthrogryposis v0.454 CHRND Zornitza Stark Deleted their comment
Mendeliome v1.3548 NUDT6 Zornitza Stark Phenotypes for gene: NUDT6 were changed from Osteogenesis imperfecta to Osteogenesis imperfecta, MONDO:0019019, NUDT6-related
Osteogenesis Imperfecta and Osteoporosis v1.12 NUDT6 Zornitza Stark Marked gene: NUDT6 as ready
Osteogenesis Imperfecta and Osteoporosis v1.12 NUDT6 Zornitza Stark Gene: nudt6 has been classified as Red List (Low Evidence).
Osteogenesis Imperfecta and Osteoporosis v1.12 NUDT6 Zornitza Stark Phenotypes for gene: NUDT6 were changed from Osteogenesis imperfecta to Osteogenesis imperfecta, MONDO:0019019, NUDT6-related
Mendeliome v1.3547 NUDT6 Zornitza Stark Marked gene: NUDT6 as ready
Mendeliome v1.3547 NUDT6 Zornitza Stark Gene: nudt6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.418 QSER1 Zornitza Stark Marked gene: QSER1 as ready
Intellectual disability syndromic and non-syndromic v1.418 QSER1 Zornitza Stark Gene: qser1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.418 Zornitza Stark Copied gene QSER1 from panel Fetal anomalies
Intellectual disability syndromic and non-syndromic v1.418 QSER1 Zornitza Stark gene: QSER1 was added
gene: QSER1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature,Literature
Mode of inheritance for gene: QSER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: QSER1 were set to PMID: 41139957
Phenotypes for gene: QSER1 were set to Neurodevelopmental disorder, MONDO:0700092, QSER1-related
Mendeliome v1.3547 QSER1 Zornitza Stark Marked gene: QSER1 as ready
Mendeliome v1.3547 QSER1 Zornitza Stark Gene: qser1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3547 QSER1 Zornitza Stark Classified gene: QSER1 as Amber List (moderate evidence)
Mendeliome v1.3547 QSER1 Zornitza Stark Gene: qser1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.467 QSER1 Zornitza Stark Marked gene: QSER1 as ready
Fetal anomalies v1.467 QSER1 Zornitza Stark Gene: qser1 has been classified as Red List (Low Evidence).
Eye Anterior Segment Abnormalities v1.16 WRAP73 Zornitza Stark Marked gene: WRAP73 as ready
Eye Anterior Segment Abnormalities v1.16 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Eye Anterior Segment Abnormalities v1.16 Zornitza Stark Copied gene WRAP73 from panel Mendeliome
Eye Anterior Segment Abnormalities v1.16 WRAP73 Zornitza Stark gene: WRAP73 was added
gene: WRAP73 was added to Eye Anterior Segment Abnormalities. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: WRAP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WRAP73 were set to 33693649
Phenotypes for gene: WRAP73 were set to Anterior segment dysgenesis, MONDO:0019503, WRAP73-related
Mendeliome v1.3546 WRAP73 Zornitza Stark Phenotypes for gene: WRAP73 were changed from Microsperophakia to Anterior segment dysgenesis, MONDO:0019503, WRAP73-related
Mendeliome v1.3545 WRAP73 Rylee Peters reviewed gene: WRAP73: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Anterior segment dysgenesis, MONDO:0019503, WRAP73-related; Mode of inheritance: None
Fetal anomalies v1.467 QSER1 Sarah Milton reviewed gene: QSER1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 41139957; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, QSER1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.467 QSER1 Sarah Milton Deleted their review
Fetal anomalies v1.467 Sarah Milton Copied gene QSER1 from panel Mendeliome
Fetal anomalies v1.467 QSER1 Sarah Milton gene: QSER1 was added
gene: QSER1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: QSER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: QSER1 were set to PMID: 41139957
Phenotypes for gene: QSER1 were set to Neurodevelopmental disorder, MONDO:0700092, QSER1-related
Mendeliome v1.3545 QSER1 Sarah Milton gene: QSER1 was added
gene: QSER1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: QSER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: QSER1 were set to PMID: 41139957
Phenotypes for gene: QSER1 were set to Neurodevelopmental disorder, MONDO:0700092, QSER1-related
Review for gene: QSER1 was set to AMBER
Added comment: QSER1 encodes glutamine and serine rich protein 1 of which the function is not clearly defined however is thought to have a role in methylation.

PMID: 41139957 describes 3 individuals with de novo heterozygous variants in QSER1 without clear consistent phenotypes.
2 individuals were born at less than 26 weeks with developmental delay with the individual that was born at term found to have normal development. Other associated features noted were ophthalmologic abnormalities (2), genitourinary abnormalities (2), congenital cardiac abnormalities (2), hemiparesis/gait abnormalities (1), preaxial polydactyly (1).

Variant types included frameshift and splice site.
One variant was present in 3 hets in gnomAD v4 with the others absent.

Functional studies demonstrated widespread expression of the protein in zebrafish without further experiments to examine molecular mechanism of variants or downstream effects.
Sources: Literature
Congenital hypothyroidism v0.77 SOX3 Chirag Patel Classified gene: SOX3 as Green List (high evidence)
Congenital hypothyroidism v0.77 SOX3 Chirag Patel Gene: sox3 has been classified as Green List (High Evidence).
Mendeliome v1.3544 SOX3 Chirag Patel Classified gene: SOX3 as Green List (high evidence)
Mendeliome v1.3544 SOX3 Chirag Patel Gene: sox3 has been classified as Green List (High Evidence).
Mendeliome v1.3543 Chirag Patel Added reviews for gene SOX3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.76 Chirag Patel Added reviews for gene SOX3 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.75 Chirag Patel Added reviews for gene THRB from panel Mendeliome
Congenital hypothyroidism v0.74 Chirag Patel Added reviews for gene THRA from panel Mendeliome
Congenital hypothyroidism v0.73 Chirag Patel Added reviews for gene TPO from panel Mendeliome
Congenital hypothyroidism v0.72 Chirag Patel Added reviews for gene TSHB from panel Mendeliome
Congenital hypothyroidism v0.71 Chirag Patel Added reviews for gene TSHR from panel Mendeliome
Congenital hypothyroidism v0.70 Chirag Patel Added reviews for gene TBL1X from panel Mendeliome
Congenital hypothyroidism v0.69 Chirag Patel Added reviews for gene SLC5A5 from panel Mendeliome
Congenital hypothyroidism v0.68 Chirag Patel Added reviews for gene SLC26A7 from panel Mendeliome
Congenital hypothyroidism v0.67 Chirag Patel Added reviews for gene SLC26A4 from panel Deafness_IsolatedAndComplex
Congenital hypothyroidism v0.66 Chirag Patel Added reviews for gene TG from panel Mendeliome
Congenital hypothyroidism v0.65 SLC16A2 Chirag Patel commented on gene: SLC16A2
Congenital hypothyroidism v0.65 Chirag Patel Added reviews for gene SLC16A2 from panel Mendeliome
Congenital hypothyroidism v0.64 Chirag Patel Added reviews for gene PROP1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.63 Chirag Patel Added reviews for gene PRKAR1A from panel Pseudohypoparathyroidism and Albright Hereditary Osteodystrophy
Congenital hypothyroidism v0.62 Chirag Patel Added reviews for gene POU1F1 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.61 Chirag Patel Added reviews for gene NKX2-1 from panel Mendeliome
Congenital hypothyroidism v0.60 Chirag Patel Added reviews for gene LHX4 from panel Pituitary hormone deficiency
Congenital hypothyroidism v0.59 Chirag Patel Added reviews for gene LHX3 from panel Mendeliome
Congenital hypothyroidism v0.58 Chirag Patel Added reviews for gene IYD from panel Mendeliome
Congenital hypothyroidism v0.57 GATA6 Chirag Patel Classified gene: GATA6 as Green List (high evidence)
Congenital hypothyroidism v0.57 GATA6 Chirag Patel Gene: gata6 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.56 GATA6 Chirag Patel Publications for gene GATA6 were changed from PMID: 31271559, 32207556, 23223019 to PMID: 31271559, 32207556, 23223019
Congenital hypothyroidism v0.55 GATA6 Chirag Patel edited their review of gene: GATA6: Added comment: PMID: 23223019 - 4 additional individuals with hypothyroidism along with typical phenotype features; Changed rating: GREEN; Changed publications: 23223019
Kabuki syndrome v0.17 Chirag Patel Added reviews for gene KMT2D from panel Mendeliome
Hypertrichosis syndromes v0.47 Chirag Patel Added reviews for gene KMT2D from panel Mendeliome
Congenital Heart Defect v0.476 Chirag Patel Added reviews for gene KMT2D from panel Mendeliome
Clefting disorders v0.279 Chirag Patel Added reviews for gene KMT2D from panel Mendeliome
Microcephaly v1.360 CCNK Sangavi Sivagnanasundram Marked gene: CCNK as ready
Microcephaly v1.360 CCNK Sangavi Sivagnanasundram Added comment: Comment when marking as ready: 4 of the reported cases presented with microcephaly
Microcephaly v1.360 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Microcephaly v1.360 Sangavi Sivagnanasundram Copied gene CCNK from panel Mendeliome
Microcephaly v1.360 CCNK Sangavi Sivagnanasundram gene: CCNK was added
gene: CCNK was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CCNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCNK were set to 41101726; 37597256; 30122539
Phenotypes for gene: CCNK were set to CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome MONDO:0035775
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Marked gene: CCNK as ready
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Classified gene: CCNK as Green List (high evidence)
Mendeliome v1.3542 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Mendeliome v1.3541 CCNK Sangavi Sivagnanasundram changed review comment from: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were either rare for AD gene or absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature; to: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.417 CCNK Sangavi Sivagnanasundram Marked gene: CCNK as ready
Intellectual disability syndromic and non-syndromic v1.417 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.417 CCNK Sangavi Sivagnanasundram Classified gene: CCNK as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.417 CCNK Sangavi Sivagnanasundram Gene: ccnk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.416 CCNK Sangavi Sivagnanasundram changed review comment from: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were either rare for AD gene or absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature; to: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.416 Sangavi Sivagnanasundram Copied gene CCNK from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.416 CCNK Sangavi Sivagnanasundram gene: CCNK was added
gene: CCNK was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCNK were set to 41101726; 37597256; 30122539
Phenotypes for gene: CCNK were set to CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome MONDO:0035775
Mendeliome v1.3541 CCNK Sangavi Sivagnanasundram gene: CCNK was added
gene: CCNK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCNK were set to 41101726; 37597256; 30122539
Phenotypes for gene: CCNK were set to CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome MONDO:0035775
Review for gene: CCNK was set to GREEN
Added comment: CCNK encodes a regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases.
Reported affected individuals presented with a syndromic neurodevelopmental disorder (i.e. DD, ID, language impairment and various dysmorphic features)
7 unrelated families with different de novo variants (missense and CNV, deletion). All variants were either rare for AD gene or absent in gnomAD v4.1.
Supportive functional studies (knockdown zebrafish and mouse model) showed recapitulation of human phenotype and was supportive of LoF as the mechanism of disease
Sources: Literature
Pituitary hormone deficiency v0.72 FOXA2 Chirag Patel Phenotypes for gene: FOXA2 were changed from No OMIM number; Congenital hyperinsulinism; Congenital hypopituitarism to Hypopituitarism, MONDO:0005152; Hyperinsulinism, MONDO:0002177
Publications for gene FOXA2 were changed from 28973288, 29329447, 30414530, 33729509, 31294511, 33999151 to 28973288, 29329447, 30414530, 33729509, 31294511, 33999151
Pituitary hormone deficiency v0.71 FGFR1 Chirag Patel Phenotypes for gene: FGFR1 were changed from Jackson-Weiss syndrome (123150); Pfeiffer syndrome (101600); Hypogonadotropic hypogonadism 2 with or without anosmia (147950); Hartsfield syndrome (615465) to Hypogonadotropic hypogonadism 2 with or without anosmia 147950
Publications for gene FGFR1 were changed from 12627230, 18034870, 16606836, 15001591 to 12627230, 18034870, 16606836, 15001591
Pituitary hormone deficiency v0.70 FGFR1 Chirag Patel reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12627230, 18034870, 16606836, 15001591; Phenotypes: Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.70 Chirag Patel Added reviews for gene FGF8 from panel Differences of Sex Development
Mendeliome v1.3540 FOXA2 Chirag Patel Phenotypes for gene: FOXA2 were changed from Hyperinsulinism MONDO:0002177 to Hyperinsulinism MONDO:0002177; Hypopituitarism, MONDO:0005152
Publications for gene FOXA2 were changed from 29329447; 28973288; 11445544; 33999151; 30414530; 33729509; 31294511 to 29329447; 28973288; 11445544; 33999151; 30414530; 33729509; 31294511
Mendeliome v1.3539 Chirag Patel Added reviews for gene FOXA2 from panel Pituitary hormone deficiency
Pituitary hormone deficiency v0.69 FOXA2 Chirag Patel reviewed gene: FOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28973288, 29329447, 30414530, 33729509, 31294511, 33999151; Phenotypes: Hypopituitarism, MONDO:0005152, Hyperinsulinism, MONDO:0002177; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.69 Chirag Patel Added reviews for gene GLI3 from panel Growth failure
Pituitary hormone deficiency v0.68 Chirag Patel Added reviews for gene GLI2 from panel Mendeliome
Pituitary hormone deficiency v0.67 Chirag Patel Added reviews for gene GHRHR from panel Mendeliome
Pituitary hormone deficiency v0.66 Chirag Patel Added reviews for gene GHR from panel Mendeliome
Pituitary hormone deficiency v0.65 Chirag Patel Added reviews for gene GH1 from panel Mendeliome
Pituitary hormone deficiency v0.64 Chirag Patel Added reviews for gene GNAI2 from panel Mendeliome
Pituitary hormone deficiency v0.63 Chirag Patel Added reviews for gene GNRHR from panel Differences of Sex Development
Pituitary hormone deficiency v0.62 HESX1 Chirag Patel reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14561704, 26781211, 11136712, 16940453; Phenotypes: Growth hormone deficiency with pituitary anomalies, MIM#182230, Pituitary hormone deficiency, combined, 5, MIM#182230, Septooptic dysplasia, MIM#182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.62 LHX3 Chirag Patel reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835633, 16394081, 17327381, 18407919; Phenotypes: Pituitary hormone deficiency, combined, 3, MIM# 221750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.62 LHX4 Chirag Patel reviewed gene: LHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 17527005, 18073311; Phenotypes: Pituitary hormone deficiency, combined, 4, MIM# 262700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.62 Chirag Patel Added reviews for gene OTX2 from panel Intellectual disability syndromic and non-syndromic
Pituitary hormone deficiency v0.61 PITX2 Chirag Patel commented on gene: PITX2
Pituitary hormone deficiency v0.61 Chirag Patel Added reviews for gene PITX2 from panel Mendeliome
Pituitary hormone deficiency v0.60 Chirag Patel Added reviews for gene PNPLA6 from panel Mendeliome
Mendeliome v1.3538 Chirag Patel Copied gene NUDT6 from panel Osteogenesis Imperfecta and Osteoporosis
Mendeliome v1.3538 NUDT6 Chirag Patel gene: NUDT6 was added
gene: NUDT6 was added to Mendeliome. Sources: Expert List
Mode of inheritance for gene: NUDT6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUDT6 were set to Osteogenesis imperfecta
Osteogenesis Imperfecta and Osteoporosis v1.11 NUDT6 Chirag Patel gene: NUDT6 was added
gene: NUDT6 was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Expert List
Mode of inheritance for gene: NUDT6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUDT6 were set to Osteogenesis imperfecta
Review for gene: NUDT6 was set to RED
Added comment: Not associated with any disease phenotype in OMIM.

The publication citation from a presentation given by Essawi et al. at the American Society of Human Genetics (ASHG 2018) conference ("A homozygous missense variant in NUDT6 is responsible for an autosomal recessive form of osteogenesis imperfecta").

A consanguineous Palestinian family with 3 affected individuals with clinical diagnosis of OI. Exome sequencing revealed a novel homozygous missense variant (c.308G>T, p.Arg103Leu) in exon 2 of NUDT6 gene. The variant segregated with the disease in the family (6 non-affected family members were either heterozygous carriers or non-carriers). NUDT6 is an expression regulator for the FGF2 gene. Functional studies show that NUDT6 was down-regulated in the proband's dermal fibroblasts and FGF2 was upregulated (RT-qPCR). Overexpression of the wild type and mutant NUDT6 gene in different cell lines showed significantly decreased levels of mutant NUDT6 RNA expression.
Sources: Expert List
Mendeliome v1.3537 TAPT1 Chirag Patel Classified gene: TAPT1 as Green List (high evidence)
Mendeliome v1.3537 TAPT1 Chirag Patel Gene: tapt1 has been classified as Green List (High Evidence).
Mendeliome v1.3536 Chirag Patel Added reviews for gene TAPT1 from panel Osteogenesis Imperfecta and Osteoporosis
Osteogenesis Imperfecta and Osteoporosis v1.10 TAPT1 Chirag Patel Classified gene: TAPT1 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v1.10 TAPT1 Chirag Patel Gene: tapt1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v1.9 TAPT1 Chirag Patel reviewed gene: TAPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37292039; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Diarrhoea v1.25 Chirag Patel Added reviews for gene UNC45A from panel Osteogenesis Imperfecta and Osteoporosis
Congenital Diarrhoea v1.24 Chirag Patel Added reviews for gene UNC45A from panel Osteogenesis Imperfecta and Osteoporosis
Osteogenesis Imperfecta and Osteoporosis v1.9 UNC45A Chirag Patel Classified gene: UNC45A as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v1.9 UNC45A Chirag Patel Gene: unc45a has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v1.8 UNC45A Chirag Patel reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35575086; Phenotypes: Osteootohepatoenteric syndrome, MIM# 619377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.240 COL4A6 Zornitza Stark Publications for gene: COL4A6 were set to 23714752; 33840813
Deafness_IsolatedAndComplex v1.239 COL4A6 Zornitza Stark changed review comment from: PMID: 41092388, two more families reported with deafness, albeit as examples of dual diagnoses.; to: PMID: 41092388, two more families reported with deafness, albeit as examples of dual diagnoses. In addition, the two variants are present in hemis in gnomADv4 (5 and 3 times). Maintain Amber rating.
Deafness_IsolatedAndComplex v1.239 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: PMID: 41092388, two more families reported with deafness, albeit as examples of dual diagnoses.; Changed publications: 23714752, 33840813, 41092388
Pituitary hormone deficiency v0.59 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Rare Disease
Mendeliome v1.3535 SRRM1 Zornitza Stark Marked gene: SRRM1 as ready
Mendeliome v1.3535 SRRM1 Zornitza Stark Gene: srrm1 has been classified as Green List (High Evidence).
Mendeliome v1.3535 Zornitza Stark Copied gene SRRM1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v1.3535 SRRM1 Zornitza Stark gene: SRRM1 was added
gene: SRRM1 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SRRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM1 were set to 41145827
Phenotypes for gene: SRRM1 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM1-related
Intellectual disability syndromic and non-syndromic v1.415 SRRM1 Zornitza Stark Marked gene: SRRM1 as ready
Intellectual disability syndromic and non-syndromic v1.415 SRRM1 Zornitza Stark Gene: srrm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.415 SRRM1 Zornitza Stark Classified gene: SRRM1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.415 SRRM1 Zornitza Stark Gene: srrm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.414 SRRM1 Zornitza Stark gene: SRRM1 was added
gene: SRRM1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRRM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM1 were set to 41145827
Phenotypes for gene: SRRM1 were set to Neurodevelopmental disorder, MONDO:0700092, SRRM1-related
Review for gene: SRRM1 was set to GREEN
Added comment: PMID 41145827 reports three individuals from three unrelated families with heterozygous truncating SRRM1 variants presenting with a neurodevelopmental disorder characterised by developmental delay, intellectual disability, short stature, behavioural and skeletal anomalies, and facial dysmorphism. Two variants are confirmed de novo and functional assays in neuronal‑like cells and Drosophila support haploinsufficiency as a disease mechanism.

Serine/arginine repetitive matrix protein 1 (SRRM1) is a key component of spliceosomes and plays various roles in messenger RNA processing.
Sources: Literature
Mendeliome v1.3534 ZNF81 Rylee Peters Tag disputed tag was added to gene: ZNF81.
Vasculitis v0.93 WDR1 Rylee Peters Tag umccr was removed from gene: WDR1.
Vasculitis v0.93 WDR1 Rylee Peters Tag umccr tag was added to gene: WDR1.
Intellectual disability syndromic and non-syndromic v1.413 SGSM3 Zornitza Stark Phenotypes for gene: SGSM3 were changed from Neurodevelopmental disorder (MONDO:0700092), SGSM3-related to Intellectual developmental disorder, autosomal recessive 84, MIM# 620401
Intellectual disability syndromic and non-syndromic v1.412 SGSM3 Zornitza Stark reviewed gene: SGSM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 84, MIM# 620401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3534 SGSM3 Zornitza Stark Phenotypes for gene: SGSM3 were changed from Neurodevelopmental disorder (MONDO:0700092), SGSM3-related to Intellectual developmental disorder, autosomal recessive 84, MIM# 620401
Mendeliome v1.3533 SGSM3 Zornitza Stark reviewed gene: SGSM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 84, MIM# 620401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3533 EPB41 Bryony Thompson Mode of inheritance for gene: EPB41 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Imprinting disorders v1.9 KHDC3L Bryony Thompson Added comment: Comment on mode of inheritance: No evidence of monoallelic association in the literature
Imprinting disorders v1.9 KHDC3L Bryony Thompson Mode of inheritance for gene: KHDC3L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3532 KHDC3L Bryony Thompson Added comment: Comment on mode of inheritance: No evidence of monoallelic association in the literature
Mendeliome v1.3532 KHDC3L Bryony Thompson Mode of inheritance for gene: KHDC3L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3531 EIF4A2 Bryony Thompson Mode of inheritance for gene: EIF4A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3530 EGR2 Bryony Thompson Mode of inheritance for gene: EGR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3529 PHGDH Sangavi Sivagnanasundram reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005786; Phenotypes: Neurometabolic disorder due to serine deficiency MONDO:0018162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v1.52 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727
Anophthalmia_Microphthalmia_Coloboma v1.51 RHOA Zornitza Stark Publications for gene: RHOA were set to 31570889
Anophthalmia_Microphthalmia_Coloboma v1.50 RHOA Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 40414526; Phenotypes: Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3529 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy to Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727
Mendeliome v1.3528 RHOA Zornitza Stark Publications for gene: RHOA were set to 31570889; 31821646
Mendeliome v1.3527 RHOA Zornitza Stark edited their review of gene: RHOA: Changed phenotypes: Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727
Mendeliome v1.3527 RHOA Zornitza Stark edited their review of gene: RHOA: Added comment: PMID 40414526: non-mosaic individual reported.; Changed publications: 31821646, 40414526
Incidentalome v0.366 TARDBP Zornitza Stark Marked gene: TARDBP as ready
Incidentalome v0.366 TARDBP Zornitza Stark Gene: tardbp has been classified as Green List (High Evidence).
Incidentalome v0.366 TARDBP Zornitza Stark Phenotypes for gene: TARDBP were changed from to Amyotrophic lateral sclerosis 10, with or without FTD; Frontotemporal lobar degeneration, TARDBP-related (MIM#612069; MONDO: 0012790)
Incidentalome v0.365 TARDBP Zornitza Stark Publications for gene: TARDBP were set to
Incidentalome v0.364 TARDBP Zornitza Stark Mode of inheritance for gene: TARDBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.363 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Incidentalome v0.363 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Incidentalome v0.363 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from to Amyotrophic lateral sclerosis 5, juvenile, MIM# 602099
Incidentalome v0.362 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Incidentalome v0.361 SPG11 Zornitza Stark Mode of inheritance for gene: SPG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.359 CARS Zornitza Stark Marked gene: CARS as ready
Microcephaly v1.359 CARS Zornitza Stark Gene: cars has been classified as Green List (High Evidence).
Microcephaly v1.359 CARS Zornitza Stark Tag new gene name tag was added to gene: CARS.
Microcephaly v1.359 Zornitza Stark Copied gene CARS from panel Mendeliome
Microcephaly v1.359 CARS Zornitza Stark gene: CARS was added
gene: CARS was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARS were set to 41121266; 39963003; 30824121
Phenotypes for gene: CARS were set to Microcephaly, developmental delay, and brittle hair syndrome, MIM# 618891
Mendeliome v1.3527 CARS Zornitza Stark Tag new gene name tag was added to gene: CARS.
Mendeliome v1.3527 CARS Zornitza Stark Phenotypes for gene: CARS were changed from Intellectual disability; microcephaly; brittle hair and nails to Microcephaly, developmental delay, and brittle hair syndrome, MIM# 618891
Mendeliome v1.3526 CARS Zornitza Stark Publications for gene: CARS were set to PMID: 30824121
Mendeliome v1.3525 CARS Zornitza Stark reviewed gene: CARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 41121266, 39963003, 30824121; Phenotypes: Microcephaly, developmental delay, and brittle hair syndrome, MIM# 618891; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.412 CARS Zornitza Stark Marked gene: CARS as ready
Intellectual disability syndromic and non-syndromic v1.412 CARS Zornitza Stark Added comment: Comment when marking as ready: New gene name is CARS1.
Intellectual disability syndromic and non-syndromic v1.412 CARS Zornitza Stark Gene: cars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.412 CARS Zornitza Stark Tag new gene name tag was added to gene: CARS.
Arthrogryposis v0.454 COL12A1 Zornitza Stark Marked gene: COL12A1 as ready
Arthrogryposis v0.454 COL12A1 Zornitza Stark Added comment: Comment when marking as ready: More severe end of the phenotype associated with biallelic disease is associated with arthrogryposis.
Arthrogryposis v0.454 COL12A1 Zornitza Stark Gene: col12a1 has been classified as Green List (High Evidence).
Arthrogryposis v0.454 COL12A1 Zornitza Stark Phenotypes for gene: COL12A1 were changed from to Ullrich congenital muscular dystrophy 2 , MIM# 616470
Arthrogryposis v0.453 COL12A1 Zornitza Stark Publications for gene: COL12A1 were set to
Arthrogryposis v0.452 COL12A1 Zornitza Stark Mode of inheritance for gene: COL12A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.451 Zornitza Stark Added reviews for gene COL12A1 from panel Muscular dystrophy and myopathy_Paediatric
Arthrogryposis v0.450 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Arthrogryposis v0.450 CHRNE Zornitza Stark Gene: chrne has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.450 CHRNE Zornitza Stark Phenotypes for gene: CHRNE were changed from to Congenital myasthenic syndrome 4, MONDO:1040021
Arthrogryposis v0.449 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Arthrogryposis v0.448 CHRNE Zornitza Stark Mode of inheritance for gene: CHRNE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.447 CHRNE Zornitza Stark Classified gene: CHRNE as Amber List (moderate evidence)
Arthrogryposis v0.447 CHRNE Zornitza Stark Gene: chrne has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.446 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: AMBER; Mode of pathogenicity: None; Publications: 33193787; Phenotypes: Congenital myasthenic syndrome 4, MONDO:1040021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.446 Zornitza Stark Added reviews for gene CHRND from panel Hydrops fetalis
Arthrogryposis v0.445 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Arthrogryposis v0.445 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Arthrogryposis v0.445 CHRNA1 Zornitza Stark Phenotypes for gene: CHRNA1 were changed from to Multiple pterygium syndrome, lethal type, MIM# 253290
Arthrogryposis v0.444 CHRNA1 Zornitza Stark Mode of inheritance for gene: CHRNA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.443 CHRNA1 Zornitza Stark changed review comment from: Typically presents with cystic hygroma/hydrops.; to: Typically presents with cystic hygroma/hydrops, contractures are part of the phenotype.
Arthrogryposis v0.443 Zornitza Stark Added reviews for gene CHRNA1 from panel Hydrops fetalis
Fetal anomalies v1.466 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254 to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Fetal anomalies v1.465 PAN2 Zornitza Stark edited their review of gene: PAN2: Changed phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Intellectual disability syndromic and non-syndromic v1.412 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254 to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Intellectual disability syndromic and non-syndromic v1.411 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3525 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254, PAN2-related to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Mendeliome v1.3524 PAN2 Zornitza Stark edited their review of gene: PAN2: Changed phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Congenital Heart Defect v0.475 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254 to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Congenital Heart Defect v0.474 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384; Mode of inheritance: None
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.160 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Syndromic disease MONDO:0002254 to Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.159 PAN2 Zornitza Stark edited their review of gene: PAN2: Changed phenotypes: Developmental delay with variable cardiac and renal congenital anomalies and dysmoprhic facies, MIM# 621384
Susceptibility to Viral Infections v1.3 IL27RA Zornitza Stark Phenotypes for gene: IL27RA were changed from Epstein-Barr virus infection MONDO:0005111 , IL27RA-related to Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405
Susceptibility to Viral Infections v1.2 IL27RA Zornitza Stark reviewed gene: IL27RA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405; Mode of inheritance: None
Disorders of immune dysregulation v1.34 IL27RA Zornitza Stark Phenotypes for gene: IL27RA were changed from Epstein-Barr virus infection MONDO:0005111 , IL27RA-related to Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405
Disorders of immune dysregulation v1.33 IL27RA Zornitza Stark reviewed gene: IL27RA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405; Mode of inheritance: None
Mendeliome v1.3524 IL27RA Zornitza Stark Phenotypes for gene: IL27RA were changed from Epstein-Barr virus infection MONDO:0005111 , IL27RA-related to Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405
Mendeliome v1.3523 IL27RA Zornitza Stark reviewed gene: IL27RA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 134 (Epstein-Barr virus-specific), MIM# 621405; Mode of inheritance: None
Brain Calcification v1.100 Zornitza Stark Copied gene RRP12 from panel Mendeliome
Brain Calcification v1.100 RRP12 Zornitza Stark gene: RRP12 was added
gene: RRP12 was added to Brain Calcification. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: RRP12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP12 were set to PMID: 41059649
Phenotypes for gene: RRP12 were set to Syndromic disease, MONDO:0002254, RRP12-related; Brain calcifications
Penetrance for gene: RRP12 were set to unknown
Mendeliome v1.3523 RRP12 Zornitza Stark Marked gene: RRP12 as ready
Mendeliome v1.3523 RRP12 Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3523 RRP12 Zornitza Stark Phenotypes for gene: RRP12 were changed from Brain calcifications to Syndromic disease, MONDO:0002254, RRP12-related; Brain calcifications
Mendeliome v1.3522 RRP12 Zornitza Stark Mode of pathogenicity for gene: RRP12 was changed from Other to None
Mendeliome v1.3521 RRP12 Zornitza Stark Classified gene: RRP12 as Amber List (moderate evidence)
Mendeliome v1.3521 RRP12 Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3520 RRP12 Catherine Dalzell gene: RRP12 was added
gene: RRP12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RRP12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP12 were set to PMID: 41059649
Phenotypes for gene: RRP12 were set to Brain calcifications
Penetrance for gene: RRP12 were set to unknown
Mode of pathogenicity for gene: RRP12 was set to Other
Review for gene: RRP12 was set to AMBER
Added comment: Variants: 5 individuals from 3 unrelated families with homozygous RRP12 variants (3 different variants, 2 consanguineous families with same variant, 2 siblings with same variant).

Phenotype: all individuals had brain calcifications (varying distribution, severity and age of onset). The patients from the two consanguineous families both had infantile-onset generalised dystonia, spasticity and severe speech impairment with widespread brain calcifications. One also had microcephaly, seizures and a cataract whilst the other had mild thrombocytopenia. The two siblings had psychiatric symptoms (one bipolar disease and one anxiety) with marked, bilateral symmetric calcifications. One also had cerebellar ataxia, choreic movements, cognitive impairment and subtle Parkinsonism whilst the other had chronic tinnitus. The final individual had dizziness and only faint bilateral lenticular calcifications.

Functional data: a statistically significant reduction in RRP12 protein levels in probands’ fibroblasts compared to controls was demonstrated. rrp12 knockdown in zebrafish embryos demonstrated reduced survival (50% survival at 2 days and maximum survival of 6 days compared to 100% survival at 6 days in controls). Phenotype abnormalities (delayed development and crimping) were also seen in the rrp12 knockdown embryos. Functional studies support a possible LoF mechanism.
Sources: Literature
Vascular Malformations SuperPanel v1.69 Bryony Thompson Changed child panels to: Vascular Malformations_Somatic; Mosaic skin disorders; Vascular Malformations_Germline; Cerebral vascular malformations; Lymphoedema_nonsyndromic; Lymphoedema_syndromic
Intellectual disability syndromic and non-syndromic v1.411 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, MIM# 615599 to Intellectual development disorder, autosomal recessive 40, MIM# 615599
Intellectual disability syndromic and non-syndromic v1.410 TAF2 Zornitza Stark edited their review of gene: TAF2: Changed phenotypes: Intellectual development disorder, autosomal recessive 40, MIM# 615599
Microcephaly v1.358 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, MIM# 615599 to Intellectual development disorder, autosomal recessive 40, MIM# 615599
Microcephaly v1.357 TAF2 Zornitza Stark edited their review of gene: TAF2: Changed phenotypes: Intellectual development disorder, autosomal recessive 40, MIM# 615599
Mendeliome v1.3520 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, MIM# 615599 to Intellectual development disorder, autosomal recessive 40, MIM# 615599
Mendeliome v1.3519 TAF2 Zornitza Stark edited their review of gene: TAF2: Changed phenotypes: Intellectual development disorder, autosomal recessive 40, MIM# 615599
Callosome v0.568 TAF2 Zornitza Stark Marked gene: TAF2 as ready
Callosome v0.568 TAF2 Zornitza Stark Gene: taf2 has been classified as Green List (High Evidence).
Callosome v0.568 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from Intellectual disability, autosomal recessive 40, MIM# 615599 to Intellectual development disorder, autosomal recessive 40, MIM# 615599
Callosome v0.567 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from intellectual disability; epilepsy; thin corpus callosum to Intellectual disability, autosomal recessive 40, MIM# 615599
Callosome v0.566 TAF2 Zornitza Stark Classified gene: TAF2 as Green List (high evidence)
Callosome v0.566 TAF2 Zornitza Stark Gene: taf2 has been classified as Green List (High Evidence).
Renal Tubulointerstitial Disease v1.7 JAG1 Chirag Patel changed review comment from: Kidney malformations and chronic kidney disease are well established in Alagille syndrome.

3 large families (out of 203) with ADTKD and a (likely) pathogenic variant in JAG1 gene segregating with disease. JAG1 expression studies as well ER stress analysis suggested that the tubulointerstitial kidney disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.

None of the 23 adult patients with isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy) had syndromic manifestations of Alagille syndrome (i.e. liver, bile duct, heart, eye, or skeletal). Therefore, JAG1 variants should be considered in isolated tubulointerstitial kidney disease.
Sources: Literature; to: Kidney malformations and chronic kidney disease are well established in Alagille syndrome.

3 large families (out of 203) with ADTKD and a (likely) pathogenic variant in JAG1 gene segregating with disease (p.Trp288*, p.Arg201Cys, and c.2372+3_2372+6del). None of the 23 adult patients in the 3 families had syndromic manifestations of Alagille syndrome (i.e. liver, bile duct, heart, eye, or skeletal), but only had isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy). JAG1 expression studies as well ER stress analysis suggested that the tubulointerstitial kidney disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function. Therefore, JAG1 variants should be considered in isolated tubulointerstitial kidney disease.
Sources: Literature
Callosome v0.565 TAF2 Boris Keren gene: TAF2 was added
gene: TAF2 was added to Callosome. Sources: Literature
Mode of inheritance for gene: TAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF2 were set to PMID: 34474177
Phenotypes for gene: TAF2 were set to intellectual disability; epilepsy; thin corpus callosum
Penetrance for gene: TAF2 were set to Complete
Mode of pathogenicity for gene: TAF2 was set to Other
Review for gene: TAF2 was set to GREEN
gene: TAF2 was marked as current diagnostic
Added comment: Most patients have severe intellectual disability, microcephaly, thin corpus callosum. 9 reported patients from 4 families.
Only missenses are reported for now but the mechanism is currently unknown
Sources: Literature
Arthrogryposis v0.442 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Arthrogryposis v0.442 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Arthrogryposis v0.442 KAT6B Zornitza Stark Phenotypes for gene: KAT6B were changed from to KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Arthrogryposis v0.441 KAT6B Zornitza Stark Publications for gene: KAT6B were set to
Arthrogryposis v0.440 KAT6B Zornitza Stark Mode of inheritance for gene: KAT6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.439 KAT6B Zornitza Stark changed review comment from: Contractures are a feature of the syndrome.; to: Contractures are a feature of the syndrome, specifically the GPS end of the spectrum.
Arthrogryposis v0.439 KAT6B Zornitza Stark edited their review of gene: KAT6B: Changed publications: 22715153
Arthrogryposis v0.439 KAT6B Zornitza Stark reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: KAT6B-related multiple congenital anomalies syndrome MONDO:0036042; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.439 KLHL7 Zornitza Stark Marked gene: KLHL7 as ready
Arthrogryposis v0.439 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Arthrogryposis v0.439 KLHL7 Zornitza Stark Phenotypes for gene: KLHL7 were changed from to PERCHING syndrome, MIM# 617055
Arthrogryposis v0.438 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Arthrogryposis v0.437 KLHL7 Zornitza Stark Mode of inheritance for gene: KLHL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.436 KLHL7 Zornitza Stark edited their review of gene: KLHL7: Changed phenotypes: PERCHING syndrome, MIM# 617055
Arthrogryposis v0.436 KLHL7 Zornitza Stark edited their review of gene: KLHL7: Changed publications: 27392078, 30142437, 29074562
Arthrogryposis v0.436 KLHL7 Zornitza Stark reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.436 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
Arthrogryposis v0.436 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Arthrogryposis v0.436 ERCC8 Zornitza Stark Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome, type A, MIM# 216400
Arthrogryposis v0.435 ERCC8 Zornitza Stark Mode of inheritance for gene: ERCC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.434 ERCC8 Zornitza Stark reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cockayne syndrome, type A, MIM# 216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.434 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Arthrogryposis v0.434 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Arthrogryposis v0.434 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from to Cerebrooculofacioskeletal syndrome 1, MIM# 214150
Arthrogryposis v0.433 ERCC6 Zornitza Stark Mode of inheritance for gene: ERCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.432 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 1, MIM# 214150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.432 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Arthrogryposis v0.432 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Arthrogryposis v0.432 ASXL1 Zornitza Stark Phenotypes for gene: ASXL1 were changed from to Bohring-Opitz syndrome , MIM#605039
Arthrogryposis v0.431 ASXL1 Zornitza Stark Mode of inheritance for gene: ASXL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Arthrogryposis v0.430 ASXL1 Zornitza Stark changed review comment from: Well established gene-disease association. Arthrogryposis is key feature.; to: Well established gene-disease association. Contractures are a key feature.
Arthrogryposis v0.430 ASXL1 Zornitza Stark reviewed gene: ASXL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bohring-Opitz syndrome , MIM#605039; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.430 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Arthrogryposis v0.430 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Arthrogryposis v0.430 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from to Congenital myopathy 2C, severe infantile, autosomal dominant, MIM# 620278
Arthrogryposis v0.429 ACTA1 Zornitza Stark Publications for gene: ACTA1 were set to
Arthrogryposis v0.428 ACTA1 Zornitza Stark Mode of inheritance for gene: ACTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v0.427 ACTA1 Zornitza Stark edited their review of gene: ACTA1: Changed publications: 38666792
Arthrogryposis v0.427 ACTA1 Zornitza Stark reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 2C, severe infantile, autosomal dominant, MIM# 620278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Homologous_recombination_deficiency_WTS_UMCCR v0.45 Zornitza Stark Panel status changed from retired to public
Immune_markers_WTS_UMCCR v0.77 Zornitza Stark Panel status changed from retired to public
Deafness_IsolatedAndComplex v1.239 OSBPL2 Zornitza Stark Publications for gene: OSBPL2 were set to 25077649; 25759012; 31451425; 30894143
Deafness_IsolatedAndComplex v1.238 OSBPL2 Zornitza Stark changed review comment from: At least three families reported, variants segregated with disease over many generations/family members; animal model.; to: At least three families reported for mono-allelic association, variants segregated with disease over many generations/family members; animal model.
Deafness_IsolatedAndComplex v1.238 OSBPL2 Zornitza Stark edited their review of gene: OSBPL2: Added comment: PMID 38701954 proposes bi-allelic association with disease but single family only with two affected siblings. One variant is splice site and the other 3'UTR. RED for bi-allelic disease.; Changed publications: 25077649, 25759012, 31451425, 30894143, 38701954; Changed phenotypes: Deafness, autosomal dominant 67, MIM# 616340, Dyschromatosis, ichthyosis, deafness, and atopic disease, MIM# 621400
Mendeliome v1.3519 OSBPL2 Zornitza Stark Publications for gene: OSBPL2 were set to 25077649; 25759012; 31451425; 30894143
Mendeliome v1.3518 OSBPL2 Zornitza Stark reviewed gene: OSBPL2: Rating: RED; Mode of pathogenicity: None; Publications: 38701954; Phenotypes: Dyschromatosis, ichthyosis, deafness, and atopic disease, MIM# 621400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Stroke v1.29 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from Cathepsin A-related Arteriopathy With Strokes and Leukoencephalopathy (CARASAL) to Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Stroke v1.28 CTSA Zornitza Stark edited their review of gene: CTSA: Changed phenotypes: Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Leukodystrophy - adult onset v0.152 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from Cathepsin-A-related arteriopathy with strokes and leukoencephalopathy to Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Leukodystrophy - adult onset v0.151 CTSA Zornitza Stark edited their review of gene: CTSA: Changed phenotypes: Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Mendeliome v1.3518 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy to Galactosialidosis, MIM# 256540; Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Mendeliome v1.3517 CTSA Zornitza Stark edited their review of gene: CTSA: Changed phenotypes: Galactosialidosis, MIM# 256540, Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394
Mendeliome v1.3517 EPO Zornitza Stark Phenotypes for gene: EPO were changed from erythrocytosis, familial, 5 MONDO:0033483 to Erythrocytosis, familial, 5, MIM# 617907; Diamond-Blackfan anaemia-like, MIM# 617911
Mendeliome v1.3516 EPO Zornitza Stark Publications for gene: EPO were set to 27651169; 29514032; 25985138; 28283061
Mendeliome v1.3515 EPO Zornitza Stark Mode of pathogenicity for gene: EPO was changed from Other to None
Mendeliome v1.3514 EPO Zornitza Stark Mode of inheritance for gene: EPO was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3513 EPO Zornitza Stark reviewed gene: EPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 27651169, 29514032, 32130275, 20700488, 30507031, 28283061, 41137542; Phenotypes: Erythrocytosis, familial, 5, MIM# 617907, Diamond-Blackfan anaemia-like, MIM# 617911; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.35 EPO Zornitza Stark Publications for gene: EPO were set to 27651169; 29514032; 32130275; 20700488; 30507031; 28283061
Red cell disorders v1.34 EPO Zornitza Stark Mode of inheritance for gene: EPO was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.33 EPO Zornitza Stark changed review comment from: PMID 41137542: further report of homozygous missense variant causing DBAL phenotype.; to: PMID 41137542: further report of homozygous missense variant causing DBAL phenotype. Amber for bi-allelic association.
Red cell disorders v1.33 EPO Zornitza Stark edited their review of gene: EPO: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.33 EPO Zornitza Stark commented on gene: EPO: Mono-allelic disorder postulated to be GoF while bi-allelic disorder postulated to be LoF.
Red cell disorders v1.33 EPO Zornitza Stark edited their review of gene: EPO: Added comment: PMID 41137542: further report of homozygous missense variant causing DBAL phenotype.; Changed publications: 27651169, 29514032, 32130275, 20700488, 30507031, 28283061, 41137542; Changed phenotypes: Erythrocytosis, familial, 5, MIM# 617907, Diamond-Blackfan anaemia-like, MIM# 617911
Defects of intrinsic and innate immunity v1.21 IRF3 Bryony Thompson Publications for gene: IRF3 were set to 26216125; 20660188; 26513235
Susceptibility to Viral Infections v1.2 IRF3 Bryony Thompson Publications for gene: IRF3 were set to 26216125; 20660188; 26513235
Defects of intrinsic and innate immunity v1.20 IRF3 Bryony Thompson reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32972995, 38665565, 33386334, 41065760, 26216125, 26513235; Phenotypes: Inborn error of immunity MONDO:0003778; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Susceptibility to Viral Infections v1.1 IRF3 Bryony Thompson reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32972995, 38665565, 33386334, 41065760, 26216125, 26513235; Phenotypes: Inborn error of immunity MONDO:0003778; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3513 IRF3 Bryony Thompson Publications for gene: IRF3 were set to 26513235
Mendeliome v1.3512 IRF3 Bryony Thompson reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32972995, 38665565, 33386334, 41065760, 26216125, 26513235; Phenotypes: Inborn error of immunity MONDO:0003778; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3512 IFNGR2 Zornitza Stark Deleted their comment
Mendeliome v1.3512 IFNGR2 Zornitza Stark edited their review of gene: IFNGR2: Added comment: PMID 23161749: some evidence that haploinsufficiency causes mono-allelic disease. Amber for this association.; Changed publications: 15924140, 18625743, 31222290, 23161749, 23161749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3512 NLRP12 Zornitza Stark reviewed gene: NLRP12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v2.28 NLRP12 Zornitza Stark reviewed gene: NLRP12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Familial cold autoinflammatory syndrome 2 - MIM#611762; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vasculitis v0.93 NLRP12 Zornitza Stark changed review comment from: Phenotypic overlap.; to: Phenotypic overlap. Note missense variants with GoF mechanism much better established as causative than LoF variants. LoF variants should be treated with caution, also very high gnomAD counts (in hundreds).
Intellectual disability syndromic and non-syndromic v1.410 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Intellectual disability syndromic and non-syndromic v1.410 CXorf56 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is STEEP1
Intellectual disability syndromic and non-syndromic v1.410 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.410 CXorf56 Zornitza Stark Phenotypes for gene: CXorf56 were changed from Mental retardation, X-linked 107, MIM# 301013 to Intellectual developmental disorder, X-linked 107, MIM# 301013
Intellectual disability syndromic and non-syndromic v1.409 CXorf56 Zornitza Stark Tag new gene name tag was added to gene: CXorf56.
Intellectual disability syndromic and non-syndromic v1.409 CXorf56 Zornitza Stark edited their review of gene: CXorf56: Changed phenotypes: Intellectual developmental disorder, X-linked 107, MIM# 301013
Genetic Epilepsy v1.267 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Genetic Epilepsy v1.267 CXorf56 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is STEEP1
Genetic Epilepsy v1.267 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.267 CXorf56 Zornitza Stark Tag new gene name tag was added to gene: CXorf56.
Genetic Epilepsy v1.267 CXorf56 Zornitza Stark edited their review of gene: CXorf56: Changed phenotypes: Intellectual developmental disorder, X-linked 107, MIM# 301013
Mendeliome v1.3512 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Mendeliome v1.3512 CXorf56 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is STEEP1
Mendeliome v1.3512 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Mendeliome v1.3512 CXorf56 Zornitza Stark Publications for gene: CXorf56 were set to 29374277
Mendeliome v1.3511 CXorf56 Zornitza Stark Phenotypes for gene: CXorf56 were changed from Mental retardation, X-linked 107, MIM# 301013 to Intellectual developmental disorder, X-linked 107, MIM# 301013
Mendeliome v1.3510 CXorf56 Zornitza Stark Tag new gene name tag was added to gene: CXorf56.
Pituitary hormone deficiency v0.58 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
Pituitary hormone deficiency v0.58 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Green List (High Evidence).
Ataxia v1.60 SKOR2 Zornitza Stark Phenotypes for gene: SKOR2 were changed from complex neurodevelopmental disorder with motor features MONDO:0100516 to Valence-Farazi cerebellar ataxia syndrome, MIM# 621386
Ataxia v1.59 SKOR2 Zornitza Stark reviewed gene: SKOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Valence-Farazi cerebellar ataxia syndrome, MIM# 621386; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.409 SKOR2 Zornitza Stark Phenotypes for gene: SKOR2 were changed from complex neurodevelopmental disorder with motor features MONDO:0100516 to Valence-Farazi cerebellar ataxia syndrome, MIM# 621386
Intellectual disability syndromic and non-syndromic v1.408 SKOR2 Zornitza Stark edited their review of gene: SKOR2: Changed phenotypes: Valence-Farazi cerebellar ataxia syndrome, MIM# 621386
Mendeliome v1.3510 SKOR2 Zornitza Stark Phenotypes for gene: SKOR2 were changed from complex neurodevelopmental disorder with motor features MONDO:0100516 to Valence-Farazi cerebellar ataxia syndrome, MIM# 621386
Mendeliome v1.3509 SKOR2 Zornitza Stark reviewed gene: SKOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Valence-Farazi cerebellar ataxia syndrome, MIM# 621386; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.58 PROKR2 Chirag Patel Mode of inheritance for gene PROKR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.57 PROKR2 Chirag Patel commented on gene: PROKR2: While OMIM refers to this as AD disease, hom and c.het patients are regularly reported
Het. patients have been reported as asymptomatic carriers (OMIM)

Loss of function - transfected HEK293 cells showed a reduction in signalling and maximal responses (PMID:18826963).

Dominant negative - coexpression of a mutant missense with wildtype protein resulted in reduced signalling compared to wildtype alone (PMID:29161432).
Pituitary hormone deficiency v0.57 PROKR2 Chirag Patel reviewed gene: PROKR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22319038, 25678757, 25759380, 18826963, 29161432; Phenotypes: Hypogonadotropic hypogonadism 3 with or without anosmia (244200); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.57 PROKR2 Chirag Patel Publications for gene PROKR2 were changed from 22319038; 25678757; 25759380; 18826963; 29161432 to 22319038; 25678757; 25759380; 18826963; 29161432
Pituitary hormone deficiency v0.56 PROP1 Chirag Patel Phenotypes for gene: PROP1 were changed from Pituitary hormone deficiency, combined, 2 (262600) to Pituitary hormone deficiency, combined, 2 MIM# 262600
Publications for gene PROP1 were changed from 20301521, 31090814 to 20301521, 31090814
Pituitary hormone deficiency v0.55 PROP1 Chirag Patel reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301521, 31090814; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.55 SOX2 Chirag Patel Phenotypes for gene: SOX2 were changed from Microphthalmia, syndromic 3 (206900) to Microphthalmia, syndromic 3, MIM# 206900
Publications for gene SOX2 were changed from 20301477, 16932809, 24211324, 21326281 to 20301477, 16932809, 24211324, 21326281
Pituitary hormone deficiency v0.54 SOX2 Chirag Patel reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301477, 16932809, 24211324, 21326281; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.54 TBX19 Chirag Patel Phenotypes for gene: TBX19 were changed from Adrenocorticotropic hormone deficiency (201400) to Adrenocorticotropic hormone deficiency, 201400
Publications for gene TBX19 were changed from 15613420, 31998673, 11290323, 15476446, 22170728 to 15613420, 31998673, 11290323, 15476446, 22170728
Mendeliome v1.3509 TBX19 Chirag Patel Source Victorian Clinical Genetics Services was removed from TBX19.
Source Expert List was added to TBX19.
Publications for gene TBX19 were changed from 15613420, 31998673, 11290323, 15476446, 22170728 to 15613420, 31998673, 11290323, 15476446, 22170728
Pituitary hormone deficiency v0.53 TBX19 Chirag Patel reviewed gene: TBX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 15613420, 31998673, 11290323, 15476446, 22170728; Phenotypes: Adrenocorticotropic hormone deficiency, 201400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pituitary hormone deficiency v0.53 SOX3 Chirag Patel reviewed gene: SOX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24346842, 15800844, 21289259; Phenotypes: Panhypopituitarism, X-linked (312000); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Pituitary hormone deficiency v0.53 SOX3 Chirag Patel Classified gene: SOX3 as Green List (high evidence)
Pituitary hormone deficiency v0.53 SOX3 Chirag Patel Gene: sox3 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.51 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Green List (high evidence)
Pituitary hormone deficiency v0.51 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.50 BRAF Chirag Patel Classified gene: BRAF as Green List (high evidence)
Pituitary hormone deficiency v0.50 BRAF Chirag Patel Gene: braf has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.49 BRAF Chirag Patel gene: BRAF was added
gene: BRAF was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 33795686
Phenotypes for gene: BRAF were set to Cardiofaciocutaneous syndrome, MONDO:0015280
Review for gene: BRAF was set to GREEN
Added comment: 5 unrelated patients with Cardio-Facio-Cutaneous (CFC) syndrome and 4 different missense variants in BRAF. They all had features of Septo-Optic Dysplasia with hypopituitarism. Functional studies using HEK293T cells showed that the BRAF genetic variants are pathogenic and result in activation of the ERK/MAPK pathway. Mice expressing one of the variants found BRAF p.Q257R showed abnormalities in terminal differentiation of hormone-producing cells causing hypopituitarism.
Sources: Genomics England PanelApp
Pituitary hormone deficiency v0.48 SHH Chirag Patel reviewed gene: SHH: Rating: AMBER; Mode of pathogenicity: None; Publications: 22897141; Phenotypes: Hypopituitarism, MONDO:0005152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v0.47 SHH Chirag Patel Phenotypes for gene: SHH were changed from Microphthalmia with coloboma 5 (611638); Holoprosencephaly 3 (142945) to Hypopituitarism, MONDO:0005152; Microphthalmia with coloboma 5 (611638); Holoprosencephaly 3 (142945)
Pituitary hormone deficiency v0.46 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.46 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.45 KCNQ1 Chirag Patel Phenotypes for gene: KCNQ1 were changed from Pituitary hormone deficiency; Long QT syndrome 1 (192500) to Hypopituitarism, MONDO:0005152; Long QT syndrome 1 (192500)
Pituitary hormone deficiency v0.44 KCNQ1 Chirag Patel Deleted their comment
Pituitary hormone deficiency v0.44 KCNQ1 Chirag Patel edited their review of gene: KCNQ1: Added comment: 2 missense variants in KCNQ1 [p.(Arg116Leu) or the p.(Pro369Leu)] identified in 3 unrelated families with multiple affected individuals with childhood onset of growth hormone deficiency (some with multiple pituitary hormone deficiencies). Gingival fibromatosis was only present if variant was maternally inherited. Variants segregated with disease and were absent in population databases.

The electrophysiological properties of the mutated channels were examined in whole-cell patch-clamp analyses in HEK 293 cells, in which both mutated channels (p.Arg116Leu and p.Pro369Leu) gave higher current levels than the wild-type (WT) Kv7.1 channels, and were associated with reduced pituitary hormone secretion from AtT-20 cells. KCNQ1 is expressed in mouse in postnatal pituitary somatotrope/gonadotrope cells and hypothalamic GHRH neurons. KCNQ1 is expressed in the human pituitary and hypothalamus.; Changed rating: AMBER; Changed publications: 29097701; Changed phenotypes: Hypopituitarism, MONDO:0005152; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.54 THBD Zornitza Stark Tag refuted tag was added to gene: THBD.
Pituitary hormone deficiency v0.44 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Pituitary hormone deficiency v0.44 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.44 KCNQ1 Chirag Patel Classified gene: KCNQ1 as Red List (low evidence)
Pituitary hormone deficiency v0.44 KCNQ1 Chirag Patel Gene: kcnq1 has been classified as Red List (Low Evidence).
Pituitary hormone deficiency v0.43 KCNQ1 Chirag Patel reviewed gene: KCNQ1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Combined Immunodeficiency v1.138 LCP1 Zornitza Stark Phenotypes for gene: LCP1 were changed from Bone marrow failure syndrome, MONDO:0000159, LCP1-related to Combined immunodeficiency, MONDO:0015131, LCP1-related
Combined Immunodeficiency v1.137 LCP1 Zornitza Stark Publications for gene: LCP1 were set to PMID: 38710235
Combined Immunodeficiency v1.136 LCP1 Zornitza Stark Classified gene: LCP1 as Green List (high evidence)
Combined Immunodeficiency v1.136 LCP1 Zornitza Stark Gene: lcp1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.129 LCP1 Zornitza Stark Phenotypes for gene: LCP1 were changed from Bone marrow failure syndrome, MONDO:0000159, LCP1-related to Combined immunodeficiency, MONDO:0015131, LCP1-related
Pituitary hormone deficiency v0.43 BMP4 Chirag Patel Classified gene: BMP4 as Green List (high evidence)
Pituitary hormone deficiency v0.43 BMP4 Chirag Patel Gene: bmp4 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.42 BMP4 Chirag Patel Phenotypes for gene: BMP4 were changed from Microphthalmia, syndromic 6 (607932) to Microphthalmia, syndromic 6, MIM#607932
Publications for gene BMP4 were changed from 31120642, 24289245, 18252212, 35633847 to 31120642, 24289245, 18252212, 35633847
Bone Marrow Failure v1.128 LCP1 Zornitza Stark Publications for gene: LCP1 were set to 38710235
Pituitary hormone deficiency v0.41 BMP4 Chirag Patel reviewed gene: BMP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31120642, 24289245, 18252212, 35633847; Phenotypes: Microphthalmia, syndromic 6, MIM#607932; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.127 LCP1 Zornitza Stark Classified gene: LCP1 as Green List (high evidence)
Bone Marrow Failure v1.127 LCP1 Zornitza Stark Gene: lcp1 has been classified as Green List (High Evidence).
Mendeliome v1.3508 LCP1 Zornitza Stark Phenotypes for gene: LCP1 were changed from Bone marrow failure syndrome, MONDO:0000159, LCP1-related to Combined immunodeficiency, MONDO:0015131, LCP1-related
Mendeliome v1.3507 LCP1 Zornitza Stark Publications for gene: LCP1 were set to 38710235
Mendeliome v1.3506 LCP1 Zornitza Stark Classified gene: LCP1 as Green List (high evidence)
Mendeliome v1.3506 LCP1 Zornitza Stark Gene: lcp1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.41 TGIF1 Chirag Patel Classified gene: TGIF1 as Amber List (moderate evidence)
Pituitary hormone deficiency v0.41 TGIF1 Chirag Patel Gene: tgif1 has been classified as Amber List (Moderate Evidence).
Pituitary hormone deficiency v0.40 TGIF1 Chirag Patel Phenotypes for gene: TGIF1 were changed from Holoprosencephaly 4 (142946) to Holoprosencephaly 4, MONDO:0007734
Publications for gene TGIF1 were changed from 23476075, 34440302 to 23476075, 34440302
Pituitary hormone deficiency v0.39 TGIF1 Chirag Patel reviewed gene: TGIF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23476075, 34440302; Phenotypes: Holoprosencephaly 4, MONDO:0007734; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.135 LCP1 Sarah Milton reviewed gene: LCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40510848, 41056520; Phenotypes: Combined immunodeficiency, MONDO:0015131, LCP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.126 LCP1 Sarah Milton reviewed gene: LCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40510848, 41056520; Phenotypes: Combined immunodeficiency, MONDO:0015131, LCP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3505 LCP1 Sarah Milton changed review comment from: LCP1 encodes lymphocyte cytosolic protein and has a role in actin cross-linking in haematopoietic cells.

PMID: 41056520 describes 4 families with 10 affected individuals who presented with neutropenia +/- lymphopenia and hypogammaglobulinemia. 2 individuals developed acute leukemia.

Variant type included missense, splice and inframe del. Appears there is some genotype phenotype correlation in regards to severity of disease.
All variants appropriately rare in gnomAD v4.

Supportive functional studies with IPSC produced with variant seen in affected individuals, these haematopoietic progenitors failed to produce CFU-G colonies with rescue upon introduction of gene corrected cells.

PMID: 41056520 describes additional family with 5 affected individuals who also had neutropenia +/- lymphopenia, hypogammaglobulinemia as well as deafness.; to: LCP1 encodes lymphocyte cytosolic protein and has a role in actin cross-linking in haematopoietic cells.

PMID: 41056520 describes 4 families with 10 affected individuals who presented with neutropenia +/- lymphopenia and hypogammaglobulinemia. 2 individuals developed acute leukemia.

Variant type included missense, splice and inframe del. Appears there is some genotype phenotype correlation in regards to severity of disease.
All variants appropriately rare in gnomAD v4.

Supportive functional studies with IPSC produced with variant seen in affected individuals, these haematopoietic progenitors failed to produce CFU-G colonies with rescue upon introduction of gene corrected cells.
Exact mechanism of disease remains unclear.

PMID: 41056520 describes additional family with 5 affected individuals who also had neutropenia +/- lymphopenia, hypogammaglobulinemia as well as deafness.
Mendeliome v1.3505 LCP1 Sarah Milton reviewed gene: LCP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40510848, PMID: 41056520; Phenotypes: Combined immunodeficiency, MONDO:0015131, LCP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 FSHR Zornitza Stark Marked gene: FSHR as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.29 SLC34A1 Chirag Patel Source KidGen_CalcPhos v38.1.0 was removed from SLC34A1.
Source Victorian Clinical Genetics Services was removed from SLC34A1.
Source Expert List was added to SLC34A1.
Mode of inheritance for gene SLC34A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SLC34A1 were changed from Hypercalcaemia, infantile, 2 MIM#616963 to Hypercalcaemia, infantile, 2 MIM#616963; Nephrolithiasis/osteoporosis, hypophosphatemic, 1, MIM#612286
Publications for gene SLC34A1 were changed from 26047794; 33516786; 33099630; 32866123; 31188746; 30943683; 12324554, 25050900, 9560283 to 26047794; 33516786; 33099630; 32866123; 31188746; 30943683; 12324554, 25050900, 9560283
Calcium and Phosphate disorders v1.28 SLC34A1 Chirag Patel reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12324554, 25050900, 9560283; Phenotypes: Nephrolithiasis/osteoporosis, hypophosphatemic, 1, MIM#612286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 FSHB Zornitza Stark Marked gene: FSHB as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 PROK2 Zornitza Stark Marked gene: PROK2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 KISS1R Zornitza Stark Marked gene: KISS1R as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 KISS1R Zornitza Stark Gene: kiss1r has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.388 KISS1R Zornitza Stark Phenotypes for gene: KISS1R were changed from Hypogonadotropic hypogonadism 8 with or without anosmia, MIM# 614837 to Hypogonadotropic hypogonadism 8 with or without anosmia, MIM# 614837
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.387 GNAS Zornitza Stark Marked gene: GNAS as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.387 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.387 LMNA Zornitza Stark Marked gene: LMNA as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.387 LMNA Zornitza Stark Gene: lmna has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.387 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from to Laminopathy (MONDO#0021106), LMNA-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 RCBTB1 Zornitza Stark Marked gene: RCBTB1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 RCBTB1 Zornitza Stark Gene: rcbtb1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v1.2 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Neurodegeneration with brain iron accumulation v1.2 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v1.2 SLC27A3 Zornitza Stark reviewed gene: SLC27A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v1.59 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Ataxia v1.59 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.408 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Intellectual disability syndromic and non-syndromic v1.408 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Regression v0.594 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Regression v0.594 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Optic Atrophy v1.54 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Optic Atrophy v1.54 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Mendeliome v1.3505 SLC27A3 Zornitza Stark Marked gene: SLC27A3 as ready
Mendeliome v1.3505 SLC27A3 Zornitza Stark Gene: slc27a3 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v1.50 YTHDC2 Zornitza Stark Marked gene: YTHDC2 as ready
Infertility and Recurrent Pregnancy Loss v1.50 YTHDC2 Zornitza Stark Gene: ythdc2 has been classified as Green List (High Evidence).
Mendeliome v1.3505 YTHDC2 Zornitza Stark Marked gene: YTHDC2 as ready
Mendeliome v1.3505 YTHDC2 Zornitza Stark Gene: ythdc2 has been classified as Green List (High Evidence).
Mendeliome v1.3505 Zornitza Stark Copied gene YTHDC2 from panel Primary Ovarian Insufficiency_Premature Ovarian Failure
Mendeliome v1.3505 YTHDC2 Zornitza Stark gene: YTHDC2 was added
gene: YTHDC2 was added to Mendeliome. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: YTHDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YTHDC2 were set to 29033321, 29360036, 35138268
Phenotypes for gene: YTHDC2 were set to Primary ovarian failure, MONDO:0005387
Infertility and Recurrent Pregnancy Loss v1.50 Zornitza Stark Copied gene YTHDC2 from panel Primary Ovarian Insufficiency_Premature Ovarian Failure
Infertility and Recurrent Pregnancy Loss v1.50 YTHDC2 Zornitza Stark gene: YTHDC2 was added
gene: YTHDC2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: YTHDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YTHDC2 were set to 29033321, 29360036, 35138268
Phenotypes for gene: YTHDC2 were set to Primary ovarian failure, MONDO:0005387
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 YTHDC2 Zornitza Stark Marked gene: YTHDC2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 YTHDC2 Zornitza Stark Gene: ythdc2 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 ZSWIM7 Zornitza Stark Marked gene: ZSWIM7 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.386 ZSWIM7 Zornitza Stark Publications for gene: ZSWIM7 were set to 40991243, 34402903
Genetic Epilepsy v1.267 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903
Genetic Epilepsy v1.266 OTUD7A Zornitza Stark Classified gene: OTUD7A as Green List (high evidence)
Genetic Epilepsy v1.266 OTUD7A Zornitza Stark Gene: otud7a has been classified as Green List (High Evidence).
Genetic Epilepsy v1.265 OTUD7A Zornitza Stark Tag SV/CNV tag was added to gene: OTUD7A.
Intellectual disability syndromic and non-syndromic v1.408 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903
Intellectual disability syndromic and non-syndromic v1.407 OTUD7A Zornitza Stark Classified gene: OTUD7A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.407 OTUD7A Zornitza Stark Gene: otud7a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.406 OTUD7A Zornitza Stark Tag SV/CNV tag was added to gene: OTUD7A.
Mendeliome v1.3504 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903
Mendeliome v1.3503 OTUD7A Zornitza Stark Classified gene: OTUD7A as Green List (high evidence)
Mendeliome v1.3503 OTUD7A Zornitza Stark Gene: otud7a has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.385 FSHB Chirag Patel Source NHS GMS was removed from FSHB.
Source Expert List was added to FSHB.
Phenotypes for gene: FSHB were changed from Hypogonadotropic hypogonadism 24 without anosmia 229070 to Hypogonadotropic hypogonadism 24 without anosmia, MIM# 229070
Publications for gene FSHB were changed from 8220432, 8220432, 9624193, 9806482, 12161499 to 8220432, 8220432, 9624193, 9806482, 12161499
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.384 FSHB Chirag Patel reviewed gene: FSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 8220432, 8220432, 9624193, 9806482, 12161499; Phenotypes: Hypogonadotropic hypogonadism 24 without anosmia, MIM# 229070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.384 FSHR Chirag Patel reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7553856, 9769327, 11889179, 20087398, 36704038; Phenotypes: Ovarian dysgenesis 1, MIM# 233300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.384 FSHR Chirag Patel Source Royal Melbourne Hospital was removed from FSHR.
Source Expert List was added to FSHR.
Phenotypes for gene: FSHR were changed from Ovarian dysgenesis 1 233300; Ovarian response to FSH stimulation 276400 to Ovarian dysgenesis 1 MONDO:0024463
Publications for gene FSHR were changed from 7553856, 9769327, 11889179, 20087398, 36704038 to 7553856, 9769327, 11889179, 20087398, 36704038
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.383 GALT Chirag Patel Source Royal Melbourne Hospital was removed from GALT.
Source Expert List was added to GALT.
Phenotypes for gene: GALT were changed from Galactosemia, 230400 to Primary ovarian failure, MONDO:0005387; Galactosemia MIM#230400
Publications for gene GALT were changed from 39440457, 19733849, 34433538, 31042289, 34730073 to 39440457, 19733849, 34433538, 31042289, 34730073
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.382 GALT Chirag Patel reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: 39440457, 19733849, 34433538, 31042289, 34730073; Phenotypes: Primary ovarian failure, MONDO:0005387, Galactosemia MIM#230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3502 OTUD7A Zornitza Stark Tag SV/CNV tag was added to gene: OTUD7A.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.382 HSD17B4 Chirag Patel reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 20673864, 28830375; Phenotypes: Perrault syndrome 1, #MIM 233400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.382 HSD17B4 Chirag Patel Source Royal Melbourne Hospital was removed from HSD17B4.
Source Expert List was added to HSD17B4.
Phenotypes for gene: HSD17B4 were changed from Perrault syndrome 1 233400 to Perrault syndrome 1, #MIM 233400
Publications for gene HSD17B4 were changed from 20673864, 28830375 to 20673864, 28830375
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.381 PMM2 Chirag Patel Source NHS GMS was removed from PMM2.
Source Expert List was added to PMM2.
Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia 212065 to Primary ovarian failure, MONDO:0005387; Congenital disorder of glycosylation, type Ia 212065
Publications for gene PMM2 were changed from 20301289, 31902100, 25497157, 33583911 to 20301289, 31902100, 25497157, 33583911
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.380 PMM2 Chirag Patel reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301289, 31902100, 25497157, 33583911; Phenotypes: Primary ovarian failure, MONDO:0005387, Congenital disorder of glycosylation, type Ia 212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary pigmented nodular adrenocortical disease v0.12 PDE11A Zornitza Stark Marked gene: PDE11A as ready
Primary pigmented nodular adrenocortical disease v0.12 PDE11A Zornitza Stark Gene: pde11a has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.12 PDE8B Zornitza Stark Marked gene: PDE8B as ready
Primary pigmented nodular adrenocortical disease v0.12 PDE8B Zornitza Stark Gene: pde8b has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.12 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Primary pigmented nodular adrenocortical disease v0.12 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Hypertension and Aldosterone disorders v1.16 ARMC5 Zornitza Stark Marked gene: ARMC5 as ready
Hypertension and Aldosterone disorders v1.16 ARMC5 Zornitza Stark Gene: armc5 has been classified as Red List (Low Evidence).
Mendeliome v1.3502 ARMC5 Zornitza Stark Marked gene: ARMC5 as ready
Mendeliome v1.3502 ARMC5 Zornitza Stark Gene: armc5 has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.12 ARMC5 Zornitza Stark Marked gene: ARMC5 as ready
Primary pigmented nodular adrenocortical disease v0.12 ARMC5 Zornitza Stark Gene: armc5 has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.12 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Primary pigmented nodular adrenocortical disease v0.12 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.380 WT1 Chirag Patel Source Royal Melbourne Hospital was removed from WT1.
Source Expert List was added to WT1.
Mode of inheritance for gene WT1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WT1 were changed from to Primary ovarian failure, MONDO:0005387
Publications for gene WT1 were changed from 26358501, 34845858 to 26358501, 34845858
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.379 WT1 Chirag Patel reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26358501, 34845858; Phenotypes: Primary ovarian failure, MONDO:0005387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.379 WDR11 Chirag Patel Source Royal Melbourne Hospital was removed from WDR11.
Source Expert List was added to WDR11.
Mode of inheritance for gene WDR11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WDR11 were changed from to Hypogonadotropic hypogonadism 14 with or without anosmia, MIM# 614858
Publications for gene WDR11 were changed from 20887964, 37988663, 36130823, 35722485, 32982993, 29263200 to 20887964, 37988663, 36130823, 35722485, 32982993, 29263200
Intellectual disability syndromic and non-syndromic v1.406 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to 23332918; 25205402; 31474318; 39953909
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.378 WDR11 Chirag Patel reviewed gene: WDR11: Rating: GREEN; Mode of pathogenicity: None; Publications: 20887964, 37988663, 36130823, 35722485, 32982993, 29263200; Phenotypes: Hypogonadotropic hypogonadism 14 with or without anosmia, MIM# 614858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.405 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to 23332918; 25205402; 31474318
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.378 TACR3 Chirag Patel reviewed gene: TACR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22031817, 20332248, 20194706, 20395662, 19755480, 28915117, 19079066; Phenotypes: Hypogonadotropic hypogonadism 11 with or without anosmia, MIM# 61484; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.378 TACR3 Chirag Patel Source Royal Melbourne Hospital was removed from TACR3.
Source Expert List was added to TACR3.
Mode of inheritance for gene TACR3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TACR3 were changed from to Hypogonadotropic hypogonadism 11 with or without anosmia, MIM# 614840
Publications for gene TACR3 were changed from 22031817, 20332248, 20194706, 20395662, 19755480, 28915117, 19079066 to 22031817, 20332248, 20194706, 20395662, 19755480, 28915117, 19079066
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.377 TAC3 Chirag Patel Source Royal Melbourne Hospital was removed from TAC3.
Source Expert List was added to TAC3.
Mode of inheritance for gene TAC3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TAC3 were changed from to Hypogonadotropic hypogonadism 10 with or without anosmia, MIM# 614839
Publications for gene TAC3 were changed from 20332248, 20194706, 34403359, 19079066 to 20332248, 20194706, 34403359, 19079066
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.376 TAC3 Chirag Patel reviewed gene: TAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20332248, 20194706, 34403359, 19079066; Phenotypes: Hypogonadotropic hypogonadism 10 with or without anosmia, MIM# 614839; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.278 KDM1A Zornitza Stark Marked gene: KDM1A as ready
Clefting disorders v0.278 KDM1A Zornitza Stark Gene: kdm1a has been classified as Green List (High Evidence).
Renal Tubulointerstitial Disease v1.7 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Renal Tubulointerstitial Disease v1.7 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Renal Tubulointerstitial Disease v1.6 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Renal Tubulointerstitial Disease v1.6 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.376 STAR Chirag Patel Source Royal Melbourne Hospital was removed from STAR.
Source Expert List was added to STAR.
Mode of inheritance for gene STAR was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAR were changed from to Lipoid adrenal hyperplasia, MIM# 201710
Publications for gene STAR were changed from 38913505, 36733346 to 38913505, 36733346
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.375 STAR Chirag Patel reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 38913505, 36733346; Phenotypes: Lipoid adrenal hyperplasia, MIM# 201710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulointerstitial Disease v1.6 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Renal Tubulointerstitial Disease v1.6 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.375 SEMA3A Chirag Patel Source Royal Melbourne Hospital was removed from SEMA3A.
Source Expert List was added to SEMA3A.
Mode of inheritance for gene SEMA3A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SEMA3A were changed from to Hypogonadotropic hypogonadism 16 with or without anosmia, MIM# 614897
Publications for gene SEMA3A were changed from 22416012, 22927827, 32060892, 31200363, 33819414 to 22416012, 22927827, 32060892, 31200363, 33819414
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.374 SEMA3A Chirag Patel reviewed gene: SEMA3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22416012, 22927827, 32060892, 31200363, 33819414; Phenotypes: Hypogonadotropic hypogonadism 16 with or without anosmia, MIM# 614897; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.374 PROK2 Chirag Patel Source Royal Melbourne Hospital was removed from PROK2.
Source Expert List was added to PROK2.
Mode of inheritance for gene PROK2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PROK2 were changed from to Hypogonadotropic hypogonadism 4 with or without anosmia, MIM# 610628
Publications for gene PROK2 were changed from 23341491, 18559922, 17959774, 17054399, 31200363, 33819414 to 23341491, 18559922, 17959774, 17054399, 31200363, 33819414
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.373 PROK2 Chirag Patel reviewed gene: PROK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.373 KISS1R Chirag Patel reviewed gene: KISS1R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.373 KISS1R Chirag Patel Source Royal Melbourne Hospital was removed from KISS1R.
Source Expert List was added to KISS1R.
Mode of inheritance for gene KISS1R was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KISS1R were changed from to Hypogonadotropic hypogonadism 8 with or without anosmia, MIM# 614837
Publications for gene KISS1R were changed from 23349759, 22619348, 21193544, 17164310, 14573733, 27094476, 33819414 to 23349759, 22619348, 21193544, 17164310, 14573733, 27094476, 33819414
Metal Metabolism Disorders v0.51 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to 35913762, 36562171
Metal Metabolism Disorders v0.50 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Metal Metabolism Disorders v0.50 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.372 GNAS Chirag Patel Source Royal Melbourne Hospital was removed from GNAS.
Source Expert Review was added to GNAS.
Mode of inheritance for gene GNAS was changed from to Other
Phenotypes for gene: GNAS were changed from to Pseudohypoparathyroidism Ia (103580) AD; Pseudohypoparathyroidism Ib (603233) AD; Pseudohypoparathyroidism Ic (612462) AD; Pseudopseudohypoparathyroidism (612463); Osseous heteroplasia, progressive (166350) AD; Pituitary adenoma 3, multiple types, somatic (617686)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.371 GNAS Chirag Patel reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoparathyroidism Ia (103580) AD, Pseudohypoparathyroidism Ib (603233) AD, Pseudohypoparathyroidism Ic (612462) AD, Pseudopseudohypoparathyroidism (612463), Osseous heteroplasia, progressive (166350) AD, Pituitary adenoma 3, multiple types, somatic (617686); Mode of inheritance: Other
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.371 LMNA Chirag Patel Classified gene: LMNA as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.371 LMNA Chirag Patel Gene: lmna has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.370 LMNA Chirag Patel reviewed gene: LMNA: Rating: AMBER; Mode of pathogenicity: None; Publications: 19283854; Phenotypes: Dilated cardiomyopathy 1A, MONDO:0007269, Primary ovarian failure, MONDO:0005387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.404 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171; 41040850
Intellectual disability syndromic and non-syndromic v1.403 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171; 41040850
Intellectual disability syndromic and non-syndromic v1.403 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171; 41040850
Intellectual disability syndromic and non-syndromic v1.402 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171
Intellectual disability syndromic and non-syndromic v1.401 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.401 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.400 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.400 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Regression v0.594 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to 35913762; 36562171; 41040850
Regression v0.594 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to 35913762; 36562171
Regression v0.593 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Regression v0.593 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Regression v0.592 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Regression v0.592 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.265 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171; 41040850
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.370 RCBTB1 Chirag Patel changed review comment from: POI was described in one family only; to: POI was described in only one family with 3 affected females (27486781)
Genetic Epilepsy v1.265 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.370 RCBTB1 Chirag Patel reviewed gene: RCBTB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.370 RCBTB1 Chirag Patel Classified gene: RCBTB1 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.370 RCBTB1 Chirag Patel Gene: rcbtb1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v1.264 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Genetic Epilepsy v1.264 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.369 Chirag Patel Copied gene RCBTB1 from panel Retinitis pigmentosa_Autosomal Recessive/X-linked
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.369 RCBTB1 Chirag Patel gene: RCBTB1 was added
gene: RCBTB1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RCBTB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RCBTB1 were set to 27486781
Phenotypes for gene: RCBTB1 were set to Retinal dystrophy with or without extraocular anomalies MIM#617175
Genetic Epilepsy v1.264 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Genetic Epilepsy v1.264 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Microcephaly v1.356 SLC31A1 Zornitza Stark Marked gene: SLC31A1 as ready
Microcephaly v1.356 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Microcephaly v1.357 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171; 41040850
Microcephaly v1.356 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171
Microcephaly v1.355 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Microcephaly v1.355 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Microcephaly v1.354 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Microcephaly v1.354 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Mendeliome v1.3502 PPIB Zornitza Stark Publications for gene: PPIB were set to 19781681; 32392875
Mendeliome v1.3501 PPIB Zornitza Stark Mode of inheritance for gene: PPIB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3500 PPIB Zornitza Stark edited their review of gene: PPIB: Changed publications: 19781681, 32392875, 41045073; Changed phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440, Optic atrophy (MONDO:0003608), PPIB-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic Atrophy v1.54 PPIB Zornitza Stark Tag founder tag was added to gene: PPIB.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.368 RECQL4 Chirag Patel Classified gene: RECQL4 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.368 RECQL4 Chirag Patel Gene: recql4 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.367 RECQL4 Chirag Patel gene: RECQL4 was added
gene: RECQL4 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Genomics England PanelApp
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL4 were set to 20301415, 10319867, 3138154
Phenotypes for gene: RECQL4 were set to Rothmund-Thomson syndrome, MONDO:0010002
Review for gene: RECQL4 was set to GREEN
Added comment: ClinGen definitive for Rothmund-Thomson syndrome (RTS).
POI can be a feature of RTS.
Sources: Genomics England PanelApp
Optic Atrophy v1.54 PPIB Zornitza Stark Marked gene: PPIB as ready
Optic Atrophy v1.54 PPIB Zornitza Stark Gene: ppib has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.54 PPIB Zornitza Stark Classified gene: PPIB as Amber List (moderate evidence)
Optic Atrophy v1.54 PPIB Zornitza Stark Gene: ppib has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.53 PPIB Zornitza Stark Classified gene: PPIB as Amber List (moderate evidence)
Optic Atrophy v1.53 PPIB Zornitza Stark Gene: ppib has been classified as Amber List (Moderate Evidence).
Regression v0.591 Sarah Milton Copied gene SLC27A3 from panel Mendeliome
Regression v0.591 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Regression. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Optic Atrophy v1.53 Sarah Milton Copied gene SLC27A3 from panel Mendeliome
Optic Atrophy v1.53 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Neurodegeneration with brain iron accumulation v1.2 Sarah Milton Copied gene SLC27A3 from panel Mendeliome
Neurodegeneration with brain iron accumulation v1.2 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Neurodegeneration with brain iron accumulation. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Intellectual disability syndromic and non-syndromic v1.399 Sarah Milton Copied gene SLC27A3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.399 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Ataxia v1.59 Sarah Milton Copied gene SLC27A3 from panel Mendeliome
Ataxia v1.59 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Optic Atrophy v1.52 PPIB Zornitza Stark Classified gene: PPIB as Red List (low evidence)
Optic Atrophy v1.52 PPIB Zornitza Stark Gene: ppib has been classified as Red List (Low Evidence).
Mendeliome v1.3500 SLC27A3 Sarah Milton gene: SLC27A3 was added
gene: SLC27A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC27A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A3 were set to PMID: 41054338
Phenotypes for gene: SLC27A3 were set to Inherited neurodegenerative disorder, MONDO:0024237, SLC27A3-related
Review for gene: SLC27A3 was set to RED
Added comment: SLC27A3 encodes for very long chain acyl CoA synthetase 3 which function to catalyse the formation of fatty acyl coA using long and very long chain fatty acids as substrates.

PMID: 41054338 describes one individual with a presumed homozgous stop gain variant in SLC27A3 who presented with progressive ataxia, optic atrophy, cognitive deterioration, mood disorder and progressive cortical atrophy on MRI-B.
Onset of symptoms at 18 months with significant progression from 12 years of age.
Duo exome testing performed (not segregated in both parents).

No homozygous LOF variants in gnomAD v4.

Some supportive functional data in paper with no protein expressed in patient cells as detected by western blot and patient's cells were found to have more neutral lipids than controls.

More literature is required to increase the robustness of this assertion.
Sources: Literature
Optic Atrophy v1.51 PPIB Zornitza Stark Classified gene: PPIB as Amber List (moderate evidence)
Optic Atrophy v1.51 PPIB Zornitza Stark Gene: ppib has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.366 YTHDC2 Chirag Patel Classified gene: YTHDC2 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.366 YTHDC2 Chirag Patel Gene: ythdc2 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.365 YTHDC2 Chirag Patel gene: YTHDC2 was added
gene: YTHDC2 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Genomics England PanelApp
Mode of inheritance for gene: YTHDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YTHDC2 were set to 29033321, 29360036, 35138268
Phenotypes for gene: YTHDC2 were set to Primary ovarian failure, MONDO:0005387
Review for gene: YTHDC2 was set to GREEN
Added comment: 2 different homozygous variants in YTHDC2 gene in 3 women from 2 families with early-onset POI (c. 2567C>G, p.P856R; c.1129G>T, p.E377*). They demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosis-associated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377* variant truncated the helicase core.

Ythdc2, an RNA helicase and N6-methyladenosine reader, has been shown to be a regulator of meiosis in mice.
Sources: Genomics England PanelApp
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.364 ZSWIM7 Chirag Patel Classified gene: ZSWIM7 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.364 ZSWIM7 Chirag Patel Gene: zswim7 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.363 ZSWIM7 Chirag Patel gene: ZSWIM7 was added
gene: ZSWIM7 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: ZSWIM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSWIM7 were set to 40991243, 34402903
Phenotypes for gene: ZSWIM7 were set to Primary ovarian failure, MONDO:0005387
Review for gene: ZSWIM7 was set to GREEN
Added comment: PMID: 40991243
Four french individuals with a diagnosis of premature ovarian insufficiency (POI) identified with variants in ZSWIM7

Patient 1: Homozygous deletion c.231_232del
Patient 2: Compound het c.231_232del;c.22del (p.Val8LeufsTer6)
Patient 3: Compound het c.231_232del; c.151C>T (NFE AF 0.002%)
Paitent 4: Homozygous c.176C>T p.(Arg51Ter)

PMID: 40991243
Two sisters from a consanguineous pedigree presented in adolescence with absent puberty and primary amenorrhea
Both sisters homozygous for c.173G>C and unaffected mother heterozygous for the variant
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.49 ZSWIM7 Chirag Patel Publications for gene ZSWIM7 were changed from 32719396, 33713115, 40991243, 34402903 to 32719396, 33713115, 40991243, 34402903
Mendeliome v1.3499 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Green List (high evidence)
Mendeliome v1.3499 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Green List (High Evidence).
Fetal anomalies v1.465 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Fetal anomalies v1.465 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Complement Deficiencies v1.2 FCN3 Zornitza Stark Classified gene: FCN3 as Red List (low evidence)
Complement Deficiencies v1.2 FCN3 Zornitza Stark Gene: fcn3 has been classified as Red List (Low Evidence).
Complement Deficiencies v1.2 FCN3 Zornitza Stark Classified gene: FCN3 as Red List (low evidence)
Complement Deficiencies v1.2 FCN3 Zornitza Stark Gene: fcn3 has been classified as Red List (Low Evidence).
Ciliopathies v1.94 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Renal Ciliopathies and Nephronophthisis v1.45 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Polydactyly v0.296 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Fetal anomalies v1.464 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Polydactyly v0.296 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Mendeliome v1.3498 TMEM17 Chirag Patel Phenotypes for gene: TMEM17 were changed from Meckel syndrome MONDO:0018921; TMEM17-related to Meckel syndrome MONDO:0018921, TMEM17-related
Complement Deficiencies v1.1 FCN3 Zornitza Stark edited their review of gene: FCN3: Added comment: Same hmz variant in all reported cases, some discussion in the literature about whether this is a genuine gene-disease association, downgrade to Red.; Changed rating: RED
Mendeliome v1.3497 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Renal Ciliopathies and Nephronophthisis v1.44 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Intellectual disability syndromic and non-syndromic v1.398 OTUD7A Rylee Peters reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924, 41028987; Phenotypes: Neurodevelopmental disorder with hypotonia and seizures (MIM#620790), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.295 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Polydactyly v0.295 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.44 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.44 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Fetal anomalies v1.463 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Genetic Epilepsy v1.263 OTUD7A Rylee Peters reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924, 41028987; Phenotypes: Neurodevelopmental disorder with hypotonia and seizures (MIM#620790), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3496 FCN3 Zornitza Stark Classified gene: FCN3 as Red List (low evidence)
Mendeliome v1.3496 FCN3 Zornitza Stark Gene: fcn3 has been classified as Red List (Low Evidence).
Mendeliome v1.3496 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Mendeliome v1.3496 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Mendeliome v1.3495 FCN3 Zornitza Stark edited their review of gene: FCN3: Added comment: Same recurrent hmz variant in all reported cases, downgrade.; Changed rating: RED
Fetal anomalies v1.462 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 41054827, 40841990
Mendeliome v1.3495 OTUD7A Rylee Peters reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924, 41028987; Phenotypes: Neurodevelopmental disorder with hypotonia and seizures (MIM#620790), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v1.43 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 41054827, 40841990
Polydactyly v0.294 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 41054827, 40841990
Mendeliome v1.3495 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 41054827, 40841990
Ciliopathies v1.93 TMEM17 Chirag Patel Classified gene: TMEM17 as Green List (high evidence)
Ciliopathies v1.93 TMEM17 Chirag Patel Gene: tmem17 has been classified as Green List (High Evidence).
Ciliopathies v1.92 TMEM17 Chirag Patel edited their review of gene: TMEM17: Added comment: 2 additional unrelated fetuses with clinical diagnosis of Meckel-Gruber syndrome (occipital encephalocele, polydactyly, and kidney cysts). WES identified a founder homozygous missense variant (Arg94Trp) in TMEM17 gene.

Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. The study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling.; Changed rating: GREEN; Changed publications: 40841990
Ciliopathies v1.92 TMEM17 Chirag Patel Publications for gene TMEM17 were changed from 41054827, 40841990 to 41054827, 40841990
Mendeliome v1.3495 PRKACA Chirag Patel Source Literature was removed from PRKACA.
Source Expert Review was added to PRKACA.
Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability; Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359
Publications for gene PRKACA were changed from 33058759; 31130284; 24571724, 25924874, 40066253, 37988664, 39006359 to 33058759; 31130284; 24571724, 25924874, 40066253, 37988664, 39006359
Mendeliome v1.3494 PDE11A Chirag Patel Source Victorian Clinical Genetics Services was removed from PDE11A.
Source Expert List was added to PDE11A.
Phenotypes for gene: PDE11A were changed from Pigmented nodular adrenocortical disease, primary, 2 - MIM#610475 to Pigmented nodular adrenocortical disease, primary, 2, MONDO:0012505
Publications for gene PDE11A were changed from 16767104; 18559625; 21047926; 17178847; 39006359, 20351491, 18491255, 18559625 to 16767104; 18559625; 21047926; 17178847; 39006359, 20351491, 18491255, 18559625
Mendeliome v1.3493 PDE8B Chirag Patel Source Victorian Clinical Genetics Services was removed from PDE8B.
Phenotypes for gene: PDE8B were changed from Striatal degeneration, autosomal dominant, MIM#609161 to Striatal degeneration, autosomal dominant, MIM#609161; Pigmented nodular adrenocortical disease, primary, 3, MONDO:0013616
Publications for gene PDE8B were changed from 20085714; 26769607; 26475694; 39006359, 32097969, 18272904, 25971952, 22335482, 18431404 to 20085714; 26769607; 26475694; 39006359, 32097969, 18272904, 25971952, 22335482, 18431404
Mendeliome v1.3492 Chirag Patel Copied gene ARMC5 from panel Primary pigmented nodular adrenocortical disease
Mendeliome v1.3492 ARMC5 Chirag Patel gene: ARMC5 was added
gene: ARMC5 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ARMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARMC5 were set to 39910635, 41042544, 25853793, 24283224, 24601692, 24708098, 24905064, 39006359, 32097969
Phenotypes for gene: ARMC5 were set to ACTH-independent macronodular adrenal hyperplasia 2, MONDO:0014416
Hypertension and Aldosterone disorders v1.16 ARMC5 Chirag Patel gene: ARMC5 was added
gene: ARMC5 was added to Hypertension and Aldosterone disorders. Sources: Literature
Mode of inheritance for gene: ARMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARMC5 were set to 25822102
Phenotypes for gene: ARMC5 were set to Primary aldosteronism, MONDO:0001422
Review for gene: ARMC5 was set to RED
Added comment: 12 germline ARMC5 genetic variants (9 missense and 2 intronic) in 20 unrelated and 2 related individuals in a cohort of 56 patients with primary aldosteronism.

4/9 missense variants and 2/3 intronic variants were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans. However, the variants were seen too commonly in the general population. No functional assays of the variants.

Note: ARMC5 has established association with Primary pigmented nodular adrenocortical disease.
Sources: Literature
Primary pigmented nodular adrenocortical disease v0.12 ARMC5 Chirag Patel Classified gene: ARMC5 as Green List (high evidence)
Primary pigmented nodular adrenocortical disease v0.12 ARMC5 Chirag Patel Gene: armc5 has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.11 ARMC5 Chirag Patel gene: ARMC5 was added
gene: ARMC5 was added to Primary pigmented nodular adrenocortical disease. Sources: Literature
Mode of inheritance for gene: ARMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARMC5 were set to 39910635, 41042544, 25853793, 24283224, 24601692, 24708098, 24905064, 39006359, 32097969
Phenotypes for gene: ARMC5 were set to ACTH-independent macronodular adrenal hyperplasia 2, MONDO:0014416
Review for gene: ARMC5 was set to GREEN
Added comment: Numerous cases reported and established gene-disease association.
Sources: Literature
Optic Atrophy v1.50 PPIB Rylee Peters gene: PPIB was added
gene: PPIB was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: PPIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIB were set to 41045073
Phenotypes for gene: PPIB were set to Optic atrophy (MONDO:0003608), PPIB-related
Review for gene: PPIB was set to AMBER
Added comment: PMID: 41045073 report 19 individuals from 9 families with adult‑onset autosomal dominant optic atrophy with a recurrent p.(Arg180Trp) missense variant (present in 7 hets in gnomAD v4). Segregation testing also identified the variant in 7 unaffected individuals (6 of whom were younger than 30yo). Somalier (relatedness metric) found possible distant relationships between 3 families; and 5 families have a shared haplotype, indicating a possible founder effect. Patient-derived fibroblasts showed altered mitochondrial morphology and subtle respiratory chain defects.
Sources: Literature
Mendeliome v1.3491 PPIB Rylee Peters reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 41045073; Phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440, Optic atrophy (MONDO:0003608), PPIB-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3491 PRKACA Chirag Patel reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: Other; Publications: 24571724, 25924874, 40066253, 37988664, 39006359; Phenotypes: Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary pigmented nodular adrenocortical disease v0.10 PRKACA Chirag Patel changed review comment from: 10 individuals from 8 unrelated family reported with ACTH-independent Cushing syndrome due to macronodular bilateral adrenal hyperplasia or adrenal adenomas. All individuals have chromosome duplications/triplications involving 19p13 region and PRKACA gene. Patient cells showed increased protein levels of the PKA catalytic subunit as well as increased basal protein kinase A activity, consistent with a gain of function.
Sources: Literature; to: Numerous cases reported with ACTH-independent Cushing syndrome due to macronodular bilateral adrenal hyperplasia or adrenal adenomas.

All individuals have chromosome duplications/triplications involving 19p13 region and PRKACA gene.

Patient cells showed increased protein levels of the PKA catalytic subunit as well as increased basal protein kinase A activity, consistent with a gain of function.
Primary pigmented nodular adrenocortical disease v0.10 PRKACA Chirag Patel Publications for gene: PRKACA were set to 24571724, 25924874
Primary pigmented nodular adrenocortical disease v0.9 PRKACA Chirag Patel Classified gene: PRKACA as Green List (high evidence)
Primary pigmented nodular adrenocortical disease v0.9 PRKACA Chirag Patel Gene: prkaca has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.8 PRKACA Chirag Patel gene: PRKACA was added
gene: PRKACA was added to Primary pigmented nodular adrenocortical disease. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACA were set to 24571724, 25924874
Phenotypes for gene: PRKACA were set to Pigmented nodular adrenocortical disease, primary, 4, MONDO:0014359
Mode of pathogenicity for gene: PRKACA was set to Other
Review for gene: PRKACA was set to GREEN
Added comment: 10 individuals from 8 unrelated family reported with ACTH-independent Cushing syndrome due to macronodular bilateral adrenal hyperplasia or adrenal adenomas. All individuals have chromosome duplications/triplications involving 19p13 region and PRKACA gene. Patient cells showed increased protein levels of the PKA catalytic subunit as well as increased basal protein kinase A activity, consistent with a gain of function.
Sources: Literature
Primary pigmented nodular adrenocortical disease v0.7 PDE8B Chirag Patel Classified gene: PDE8B as Green List (high evidence)
Primary pigmented nodular adrenocortical disease v0.7 PDE8B Chirag Patel Gene: pde8b has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.6 PDE8B Chirag Patel gene: PDE8B was added
gene: PDE8B was added to Primary pigmented nodular adrenocortical disease. Sources: Expert List
Mode of inheritance for gene: PDE8B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE8B were set to 39006359, 32097969, 18272904, 25971952, 22335482, 18431404
Phenotypes for gene: PDE8B were set to Pigmented nodular adrenocortical disease, primary, 3, MONDO:0013616
Review for gene: PDE8B was set to GREEN
Added comment: Numerous cases reported and established gene-disease association
Sources: Expert List
Mendeliome v1.3491 PDE8B Chirag Patel reviewed gene: PDE8B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39006359, 32097969, 18272904, 25971952, 22335482, 18431404; Phenotypes: Pigmented nodular adrenocortical disease, primary, 3, MONDO:0013616; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary pigmented nodular adrenocortical disease v0.5 PDE11A Chirag Patel Publications for gene PDE11A were changed from 39006359, 16767104, 20351491, 18491255, 18559625, 32097969 to 39006359, 16767104, 20351491, 18491255, 18559625, 32097969
Mendeliome v1.3491 PDE11A Chirag Patel Classified gene: PDE11A as Green List (high evidence)
Mendeliome v1.3491 PDE11A Chirag Patel Gene: pde11a has been classified as Green List (High Evidence).
Mendeliome v1.3490 PDE11A Chirag Patel reviewed gene: PDE11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39006359, 16767104, 20351491, 18491255, 18559625; Phenotypes: Pigmented nodular adrenocortical disease, primary, 2, MONDO:0012505; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary pigmented nodular adrenocortical disease v0.4 PDE11A Chirag Patel Classified gene: PDE11A as Green List (high evidence)
Primary pigmented nodular adrenocortical disease v0.4 PDE11A Chirag Patel Gene: pde11a has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.3 PDE11A Chirag Patel gene: PDE11A was added
gene: PDE11A was added to Primary pigmented nodular adrenocortical disease. Sources: Expert List
Mode of inheritance for gene: PDE11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE11A were set to 39006359, 16767104, 20351491, 18491255, 18559625
Phenotypes for gene: PDE11A were set to Pigmented nodular adrenocortical disease, primary, 2, MONDO:0012505
Review for gene: PDE11A was set to GREEN
Added comment: Numerous cases reported and established gene-disease association
Sources: Expert List
Primary pigmented nodular adrenocortical disease v0.2 PRKAR1A Chirag Patel Classified gene: PRKAR1A as Green List (high evidence)
Primary pigmented nodular adrenocortical disease v0.2 PRKAR1A Chirag Patel Gene: prkar1a has been classified as Green List (High Evidence).
Primary pigmented nodular adrenocortical disease v0.1 PRKAR1A Chirag Patel gene: PRKAR1A was added
gene: PRKAR1A was added to Primary pigmented nodular adrenocortical disease. Sources: Expert List
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKAR1A were set to 39006359, 12213893, 40066253, 39355138, 11115848
Phenotypes for gene: PRKAR1A were set to Pigmented nodular adrenocortical disease, primary, 1, MONDO:0012509; Carney complex type 1, MONDO:0008057
Review for gene: PRKAR1A was set to GREEN
Added comment: Pigmented nodular adrenocortical disease reported in Carney complex.
Gene-disease association is definitive in ClinGen.

Pigmented nodular adrenocortical disease can also occur in isolation with numerous cases reported.
Sources: Expert List
Primary pigmented nodular adrenocortical disease v0.0 Chirag Patel Added Panel Primary pigmented nodular adrenocortical disease
Set panel types to: Genetic Health Queensland
Metal Metabolism Disorders v0.49 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.398 AUTS2 Fahaz Nazer reviewed gene: AUTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39953909; Phenotypes: Intellectual developmental disorder, autosomal dominant 26, MIM# 615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.278 KDM1A Chirag Patel Classified gene: KDM1A as Green List (high evidence)
Clefting disorders v0.278 KDM1A Chirag Patel Gene: kdm1a has been classified as Green List (High Evidence).
Clefting disorders v0.277 KDM1A Chirag Patel reviewed gene: KDM1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26656649, 24838796, 27094131; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features 616728; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Tubulointerstitial Disease v1.4 JAG1 Chirag Patel gene: JAG1 was added
gene: JAG1 was added to Renal Tubulointerstitial Disease. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to PMID: 41061854
Phenotypes for gene: JAG1 were set to JAG1-related autosomal dominant tubulointerstitial kidney disease; Alagille syndrome, MONDO:0007318
Review for gene: JAG1 was set to GREEN
Added comment: Kidney malformations and chronic kidney disease are well established in Alagille syndrome.

3 large families (out of 203) with ADTKD and a (likely) pathogenic variant in JAG1 gene segregating with disease. JAG1 expression studies as well ER stress analysis suggested that the tubulointerstitial kidney disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.

None of the 23 adult patients with isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy) had syndromic manifestations of Alagille syndrome (i.e. liver, bile duct, heart, eye, or skeletal). Therefore, JAG1 variants should be considered in isolated tubulointerstitial kidney disease.
Sources: Literature
Renal Tubulointerstitial Disease v1.4 JAG1 Chirag Patel gene: JAG1 was added
gene: JAG1 was added to Renal Tubulointerstitial Disease. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to PMID: 41061854
Phenotypes for gene: JAG1 were set to JAG1-related autosomal dominant tubulointerstitial kidney disease; Alagille syndrome, MONDO:0007318
Review for gene: JAG1 was set to GREEN
Added comment: Kidney malformations and chronic kidney disease are well established in Alagille syndrome.

3 large families (out of 203) with ADTKD and a (likely) pathogenic variant in JAG1 gene segregating with disease. JAG1 expression studies as well ER stress analysis suggested that the tubulointerstitial kidney disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.

None of the 23 adult patients with isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy) had syndromic manifestations of Alagille syndrome (i.e. liver, bile duct, heart, eye, or skeletal). Therefore, JAG1 variants should be considered in isolated tubulointerstitial kidney disease.
Sources: Literature
Kidney Cancer v1.11 Krithika Murali removed gene:MSH6 from the panel
Kidney Cancer v1.10 Krithika Murali removed gene:MLH1 from the panel
Kidney Cancer v1.9 Krithika Murali removed gene:MSH2 from the panel
Microcephaly v1.353 Rylee Peters Copied gene SLC31A1 from panel Mendeliome
Microcephaly v1.353 SLC31A1 Rylee Peters gene: SLC31A1 was added
gene: SLC31A1 was added to Microcephaly. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171
Phenotypes for gene: SLC31A1 were set to Neurodegeneration and seizures due to copper transport defect, MIM# 620306
Intellectual disability syndromic and non-syndromic v1.398 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.590 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.263 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3490 SLC31A1 Rylee Peters reviewed gene: SLC31A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41040850; Phenotypes: Neurodegeneration and seizures due to copper transport defect MIM#620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3490 DIP2B_FRA12A_CGG Bryony Thompson Publications for STR: DIP2B_FRA12A_CGG were set to 17236128
Intellectual disability syndromic and non-syndromic v1.398 DIP2B_FRA12A_CGG Bryony Thompson Publications for STR: DIP2B_FRA12A_CGG were set to 17236128
Intellectual disability syndromic and non-syndromic v1.397 DIP2B_FRA12A_CGG Bryony Thompson edited their review of STR: DIP2B_FRA12A_CGG: Added comment: Unsure about the expansions association with disease due to variable phenotypes and possible incomplete penetrance PMID 17236128, 39854091, and 41028987 report 23 unrelated families with heterozygous CGG repeat expansions in the 5′UTR of DIP2B. Sixteen families present with intellectual disability associated with the FRA12A fragile site, while seven families (including two siblings, five ataxia probands, and one dystonia case) exhibit neurodevelopmental disability with progressive movement disorders (chorea, dystonia, ataxia). Functional studies demonstrate reduced DIP2B expression via promoter hypermethylation. Segregation analysis shows segregation from unaffected parents (possibly reduced penetrance) and de novo events. DIP2B expansion OR 2.8 (p=0.04) in ataxia cohort (5/788) vs gnomAD.; Changed publications: 17236128, 33510257, 39854091, 41028987; Changed phenotypes: intellectual disability, FRA12A type MONDO:0007634
Mendeliome v1.3489 DIP2B_FRA12A_CGG Bryony Thompson edited their review of STR: DIP2B_FRA12A_CGG: Added comment: Unsure about the expansions association with disease due to variable phenotypes and possible incomplete penetrance PMID 17236128, 39854091, and 41028987 report 23 unrelated families with heterozygous CGG repeat expansions in the 5′UTR of DIP2B. Sixteen families present with intellectual disability associated with the FRA12A fragile site, while seven families (including two siblings, five ataxia probands, and one dystonia case) exhibit neurodevelopmental disability with progressive movement disorders (chorea, dystonia, ataxia). Functional studies demonstrate reduced DIP2B expression via promoter hypermethylation. Segregation analysis shows segregation from unaffected parents (possibly reduced penetrance) and de novo events. DIP2B expansion OR 2.8 (p=0.04) in ataxia cohort (5/788) vs gnomAD.; Changed publications: 17236128, 33510257, 39854091, 41028987; Changed phenotypes: intellectual disability, FRA12A type MONDO:0007634
Repeat Disorders v0.269 DIP2B_FRA12A_CGG Bryony Thompson Phenotypes for STR: DIP2B_FRA12A_CGG were changed from Mental retardation, FRA12A type MIM#136630 to intellectual disability, FRA12A type MONDO:0007634
Repeat Disorders v0.268 DIP2B_FRA12A_CGG Bryony Thompson Publications for STR: DIP2B_FRA12A_CGG were set to 17236128; 39854091; 33510257
Repeat Disorders v0.267 DIP2B_FRA12A_CGG Bryony Thompson edited their review of STR: DIP2B_FRA12A_CGG: Added comment: Unsure about the expansions association with disease due to variable phenotypes and possible incomplete penetrance
PMID 17236128, 39854091, and 41028987 report 23 unrelated families with heterozygous CGG repeat expansions in the 5′UTR of DIP2B. Sixteen families present with intellectual disability associated with the FRA12A fragile site, while seven families (including two siblings, five ataxia probands, and one dystonia case) exhibit neurodevelopmental disability with progressive movement disorders (chorea, dystonia, ataxia). Functional studies demonstrate reduced DIP2B expression via promoter hypermethylation. Segregation analysis shows segregation from unaffected parents (possibly reduced penetrance) and de novo events. DIP2B expansion OR 2.8 (p=0.04) in ataxia cohort (5/788) vs gnomAD.; Changed publications: 17236128, 33510257, 39854091, 41028987; Changed phenotypes: intellectual disability, FRA12A type MONDO:0007634
Heterotaxy v1.44 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Heterotaxy v1.44 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Green List (High Evidence).
Heterotaxy v1.44 Zornitza Stark Copied gene CFAP74 from panel Ciliary Dyskinesia
Heterotaxy v1.44 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Heterotaxy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313; 41078601; 39362668; 36459505
Phenotypes for gene: CFAP74 were set to ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353
Ciliary Dyskinesia v1.63 CFAP74 Zornitza Stark Phenotypes for gene: CFAP74 were changed from ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353 to ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353
Ciliary Dyskinesia v1.62 CFAP74 Zornitza Stark Phenotypes for gene: CFAP74 were changed from Primary ciliary dyskinesia; infertility to ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353
Ciliary Dyskinesia v1.61 CFAP74 Zornitza Stark Publications for gene: CFAP74 were set to 32555313
Ciliary Dyskinesia v1.60 CFAP74 Zornitza Stark Classified gene: CFAP74 as Green List (high evidence)
Ciliary Dyskinesia v1.60 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.59 CFAP74 Zornitza Stark Classified gene: CFAP74 as Green List (high evidence)
Ciliary Dyskinesia v1.59 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Green List (High Evidence).
Mendeliome v1.3489 CFAP74 Zornitza Stark Phenotypes for gene: CFAP74 were changed from Primary ciliary dyskinesia; infertility to ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353
Mendeliome v1.3488 CFAP74 Zornitza Stark Classified gene: CFAP74 as Green List (high evidence)
Mendeliome v1.3488 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Green List (High Evidence).
Mendeliome v1.3487 RBM15 Zornitza Stark Marked gene: RBM15 as ready
Mendeliome v1.3487 RBM15 Zornitza Stark Gene: rbm15 has been classified as Red List (Low Evidence).
Mirror movements v1.1 RBM15 Zornitza Stark Marked gene: RBM15 as ready
Mirror movements v1.1 RBM15 Zornitza Stark Gene: rbm15 has been classified as Red List (Low Evidence).
Mendeliome v1.3487 SSPO Zornitza Stark Marked gene: SSPO as ready
Mendeliome v1.3487 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Mendeliome v1.3487 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Mendeliome v1.3487 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Genetic Epilepsy v1.263 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Genetic Epilepsy v1.263 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Genetic Epilepsy v1.263 SSPO Zornitza Stark Marked gene: SSPO as ready
Genetic Epilepsy v1.263 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Genetic Epilepsy v1.263 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Genetic Epilepsy v1.263 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Marked gene: SSPO as ready
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Classified gene: SSPO as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.397 SSPO Zornitza Stark Gene: sspo has been classified as Green List (High Evidence).
Kidney Cancer v1.8 MSH6 Krithika Murali Marked gene: MSH6 as ready
Kidney Cancer v1.8 MSH6 Krithika Murali Gene: msh6 has been classified as Green List (High Evidence).
Kidney Cancer v1.8 MSH6 Krithika Murali Classified gene: MSH6 as Green List (high evidence)
Kidney Cancer v1.8 MSH6 Krithika Murali Gene: msh6 has been classified as Green List (High Evidence).
Kidney Cancer v1.7 MSH2 Krithika Murali Marked gene: MSH2 as ready
Kidney Cancer v1.7 MSH2 Krithika Murali Gene: msh2 has been classified as Green List (High Evidence).
Kidney Cancer v1.7 MSH2 Krithika Murali Classified gene: MSH2 as Green List (high evidence)
Kidney Cancer v1.7 MSH2 Krithika Murali Gene: msh2 has been classified as Green List (High Evidence).
Kidney Cancer v1.6 MLH1 Krithika Murali Marked gene: MLH1 as ready
Kidney Cancer v1.6 MLH1 Krithika Murali Gene: mlh1 has been classified as Green List (High Evidence).
Kidney Cancer v1.6 MLH1 Krithika Murali Classified gene: MLH1 as Green List (high evidence)
Kidney Cancer v1.6 MLH1 Krithika Murali Gene: mlh1 has been classified as Green List (High Evidence).
Kidney Cancer v1.5 MLH1 Krithika Murali gene: MLH1 was added
gene: MLH1 was added to Kidney Cancer. Sources: Expert List,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MLH1 were set to PMID: 28754778
Phenotypes for gene: MLH1 were set to Lynch syndrome - MONDO:0005835; Mismatch repair cancer syndrome 1 MONDO:0010159
Review for gene: MLH1 was set to GREEN
Added comment: Elevated lifetime risk of urothelial carcinoma (mainly ureteric and renal pelvis cancers but can include bladder cancer) - PMID: 28754778; eviQ.
Sources: Expert List, Expert Review
Kidney Cancer v1.4 MSH2 Krithika Murali gene: MSH2 was added
gene: MSH2 was added to Kidney Cancer. Sources: Expert Review,Expert List
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MSH2 were set to PMID: 28754778
Phenotypes for gene: MSH2 were set to Lynch syndrome - MONDO:0005835; Mismatch repair cancer syndrome 1 MONDO:0010159
Review for gene: MSH2 was set to GREEN
Added comment: Elevated lifetime risk of urothelial carcinoma (mainly ureteric and renal pelvis cancers but can include bladder cancer) - PMID: 28754778; eviQ.
Sources: Expert Review, Expert List
Kidney Cancer v1.3 MSH6 Krithika Murali gene: MSH6 was added
gene: MSH6 was added to Kidney Cancer. Sources: Expert List,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MSH6 were set to PMID: 28754778
Phenotypes for gene: MSH6 were set to Lynch syndrome - MONDO:0005835; Mismatch repair cancer syndrome 1 MONDO:0010159
Review for gene: MSH6 was set to GREEN
Added comment: Elevated lifetime risk of urothelial carcinoma (mainly ureteric and renal pelvis cancers but can include bladder cancer) - PMID: 28754778; eviQ.
Sources: Expert List, Expert Review
Mendeliome v1.3486 PPFIA2 May Tun Hla Maw changed review comment from: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Gene-disease association: neurodevelopmental disorder.
Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature; to: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.396 Sarah Milton Copied gene SSPO from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.396 SSPO Sarah Milton gene: SSPO was added
gene: SSPO was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
new gene name tags were added to gene: SSPO.
Mode of inheritance for gene: SSPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSPO were set to PMID: 41077560
Phenotypes for gene: SSPO were set to Neurodevelopmental disorder, MONDO:0700092, SSPOP-related
Genetic Epilepsy v1.262 Sarah Milton Copied gene SSPO from panel Mendeliome
Genetic Epilepsy v1.262 SSPO Sarah Milton gene: SSPO was added
gene: SSPO was added to Genetic Epilepsy. Sources: Literature
new gene name tags were added to gene: SSPO.
Mode of inheritance for gene: SSPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSPO were set to PMID: 41077560
Phenotypes for gene: SSPO were set to Neurodevelopmental disorder, MONDO:0700092, SSPOP-related
Mendeliome v1.3486 SSPO Sarah Milton changed review comment from: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature; to: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which is a large secreted glycoprotein that plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mendeliome v1.3486 SSPO Sarah Milton gene: SSPO was added
gene: SSPO was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: SSPO.
Mode of inheritance for gene: SSPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSPO were set to PMID: 41077560
Phenotypes for gene: SSPO were set to Neurodevelopmental disorder, MONDO:0700092, SSPOP-related
Review for gene: SSPO was set to GREEN
Added comment: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mirror movements v1.1 Sangavi Sivagnanasundram Copied gene RBM15 from panel Mendeliome
Mirror movements v1.1 RBM15 Sangavi Sivagnanasundram gene: RBM15 was added
gene: RBM15 was added to Mirror movements. Sources: Literature
Mode of inheritance for gene: RBM15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBM15 were set to 41058181
Phenotypes for gene: RBM15 were set to Congenital mirror movements, RBM15-related, MONDO:0016558
Mendeliome v1.3485 RBM15 Sangavi Sivagnanasundram gene: RBM15 was added
gene: RBM15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBM15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBM15 were set to 41058181
Phenotypes for gene: RBM15 were set to Congenital mirror movements, RBM15-related, MONDO:0016558
Review for gene: RBM15 was set to RED
Added comment: One 27-year-old proband reported with mild mirror movements affecting only hands.
De novo heterozygous was identified in the affected individual and absent from asymptomatic parents - p.Ser175Lysfs∗8 - absent in gnomADv4.1
RBM15 is constraint for LOF according to gnomAD v4.1 [pLI = 1;o/e = 0.11 (0.06 - 0.21)] however, LoF isn't an established mechanism of disease.
Sources: Literature
Mendeliome v1.3484 CFAP74 Sangavi Sivagnanasundram changed review comment from: Additional reported individuals supporting gene-disease association.; to: Additional reported individuals in four unrelated families supporting gene-disease association.
Ciliary Dyskinesia v1.58 CFAP74 Sangavi Sivagnanasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 41078601, 39362668, 36459505, 32555313; Phenotypes: ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3484 CFAP74 Sangavi Sivagnanasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 41078601, 39362668, 36459505, 32555313; Phenotypes: ciliary dyskinesia, primary, 49, without situs inversus MONDO:0859353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3484 SNAI2 Sangavi Sivagnanasundram reviewed gene: SNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 41073431; Phenotypes: Waardenburg syndrome type 2D MONDO:0012144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.395 PPFIA2 Zornitza Stark Marked gene: PPFIA2 as ready
Intellectual disability syndromic and non-syndromic v1.395 PPFIA2 Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.395 Zornitza Stark Copied gene PPFIA2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.395 PPFIA2 Zornitza Stark gene: PPFIA2 was added
gene: PPFIA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PPFIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA2 were set to 41044885
Phenotypes for gene: PPFIA2 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA2 related
Mendeliome v1.3484 PPFIA2 Zornitza Stark Marked gene: PPFIA2 as ready
Mendeliome v1.3484 PPFIA2 Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence).
Mendeliome v1.3484 PPFIA2 Zornitza Stark Mode of pathogenicity for gene: PPFIA2 was changed from Other to None
Mendeliome v1.3483 PPFIA2 Zornitza Stark Classified gene: PPFIA2 as Green List (high evidence)
Mendeliome v1.3483 PPFIA2 Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence).
Congenital Myasthenia v1.18 PURA Zornitza Stark Marked gene: PURA as ready
Congenital Myasthenia v1.18 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Congenital Myasthenia v1.18 PURA Zornitza Stark Phenotypes for gene: PURA were changed from Congenital myasthenia; congenital hypoventilation to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Congenital Myasthenia v1.17 PURA Zornitza Stark Classified gene: PURA as Green List (high evidence)
Congenital Myasthenia v1.17 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Congenital Myasthenia v1.16 PURA Zornitza Stark reviewed gene: PURA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.352 EIPR1 Zornitza Stark Marked gene: EIPR1 as ready
Microcephaly v1.352 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.394 EIPR1 Zornitza Stark Marked gene: EIPR1 as ready
Intellectual disability syndromic and non-syndromic v1.394 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Microcephaly v1.352 Zornitza Stark Copied gene EIPR1 from panel Mendeliome
Microcephaly v1.352 EIPR1 Zornitza Stark gene: EIPR1 was added
gene: EIPR1 was added to Microcephaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: EIPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIPR1 were set to 41058046
Phenotypes for gene: EIPR1 were set to Mendelian neurodevelopmental disorder MONDO:0100500, EIPR1-related
Penetrance for gene: EIPR1 were set to unknown
Intellectual disability syndromic and non-syndromic v1.394 Zornitza Stark Copied gene EIPR1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.394 EIPR1 Zornitza Stark gene: EIPR1 was added
gene: EIPR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: EIPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIPR1 were set to 41058046
Phenotypes for gene: EIPR1 were set to Mendelian neurodevelopmental disorder MONDO:0100500, EIPR1-related
Penetrance for gene: EIPR1 were set to unknown
Mendeliome v1.3482 EIPR1 Zornitza Stark Marked gene: EIPR1 as ready
Mendeliome v1.3482 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Mendeliome v1.3482 EIPR1 Zornitza Stark Classified gene: EIPR1 as Green List (high evidence)
Mendeliome v1.3482 EIPR1 Zornitza Stark Gene: eipr1 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.68 ARHGAP19 Zornitza Stark Marked gene: ARHGAP19 as ready
Hereditary Neuropathy_CMT - isolated v1.68 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.68 Zornitza Stark Copied gene ARHGAP19 from panel Mendeliome
Hereditary Neuropathy_CMT - isolated v1.68 ARHGAP19 Zornitza Stark gene: ARHGAP19 was added
gene: ARHGAP19 was added to Hereditary Neuropathy_CMT - isolated. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ARHGAP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP19 were set to 41086021
Phenotypes for gene: ARHGAP19 were set to Motor Peripheral Neuropathy; MONDO:0002316; ARHGAP19 related
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Marked gene: ARHGAP19 as ready
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Classified gene: ARHGAP19 as Green List (high evidence)
Mendeliome v1.3481 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Mendeliome v1.3480 AGBL3 Bryony Thompson Marked gene: AGBL3 as ready
Mendeliome v1.3480 AGBL3 Bryony Thompson Gene: agbl3 has been classified as Red List (Low Evidence).
Mendeliome v1.3480 AGBL3 Bryony Thompson gene: AGBL3 was added
gene: AGBL3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGBL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGBL3 were set to 41042736
Phenotypes for gene: AGBL3 were set to Hypocomplementemic urticarial vasculitis MONDO:0018227
Review for gene: AGBL3 was set to RED
Added comment: PMID:41042736 reports one patient from a single consanguineous family with biallelic loss‑of‑function AGBL3 variant presenting with hypocomplementemic urticarial vasculitis syndrome, childhood‑onset fever, urticarial rash, arthralgia, and low complement levels.
Sources: Literature
Immunological disorders_SuperPanel v15.134 Bryony Thompson Changed child panels to: Autoinflammatory Disorders; Combined Immunodeficiency; Bone Marrow Failure; Phagocyte Defects; Disorders of immune dysregulation; Severe Combined Immunodeficiency; Defects of intrinsic and innate immunity; Hereditary angioedema; Autoimmune Lymphoproliferative Syndrome; Predominantly Antibody Deficiency; Susceptibility to Viral Infections; Complement Deficiencies; Inflammatory bowel disease
Severe Combined Immunodeficiency v1.27 Bryony Thompson Panel name changed from Severe Combined Immunodeficiency (absent T present B cells) to Severe Combined Immunodeficiency
Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v1.3479 EIPR1 Thomas Cloney gene: EIPR1 was added
gene: EIPR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIPR1 were set to 41058046
Phenotypes for gene: EIPR1 were set to Mendelian neurodevelopmental disorder MONDO:0100500, EIPR1-related
Penetrance for gene: EIPR1 were set to unknown
Review for gene: EIPR1 was set to GREEN
Added comment: Report of 8 individuals from 6 unrelated consanguinous families with homozygous EIPR1 variants (5 different variants).
Phenotype: All had global developmental delay (range of severity), with significant motor delay (5/8 never attained walking). Neurological manifestations: 2/8 Hypotonia, 4/8 had spasticity. 5/8 had microcepahly. MRI Brain abnormalities included: delayed myelination, hypoplasia of the corpus callosum, mild cerebellar atrophy, dysmorphic lateral ventricles. (Limited phenotypic information in pre-print - all in supplementary data)
Functional data: In vitro functional work show reduced protrien levels and interaction with EARP and GARP; and in vivo zebrafish models with knowckout of EIPR1 result in neurodevelopmental and locomotor defects
Sources: Literature
Congenital Myasthenia v1.16 PURA Maggie Yau gene: PURA was added
gene: PURA was added to Congenital Myasthenia. Sources: Literature
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to 36768582
Phenotypes for gene: PURA were set to Congenital myasthenia; congenital hypoventilation
Review for gene: PURA was set to GREEN
Added comment: PMID:36768582 Three cases with clinical myasthenic features confirmed with electrophysiological studies showing decremental response on repetitive nerve stimulation (RNS)
Sources: Literature
Mendeliome v1.3479 PPFIA2 May Tun Hla Maw gene: PPFIA2 was added
gene: PPFIA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPFIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA2 were set to 41044885
Phenotypes for gene: PPFIA2 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA2 related
Mode of pathogenicity for gene: PPFIA2 was set to Other
Review for gene: PPFIA2 was set to GREEN
Added comment: Encodes Liprin-alpha2.
Predominantly expressed in brain in the pre- and post-synaptic compartments.
Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains.

Gene-disease association: neurodevelopmental disorder.
Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism.

Evidence summary:
Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD.

Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia.

Functional studies:
Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype.
Sources: Literature
Severe Combined Immunodeficiency v1.26 Bryony Thompson Copied gene PSMB10 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.26 PSMB10 Bryony Thompson gene: PSMB10 was added
gene: PSMB10 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Red,Literature
Mode of inheritance for gene: PSMB10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMB10 were set to 38503300
Phenotypes for gene: PSMB10 were set to Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Severe Combined Immunodeficiency v1.25 Bryony Thompson Copied gene LCP2 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.25 LCP2 Bryony Thompson gene: LCP2 was added
gene: LCP2 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LCP2 were set to 33231617
Phenotypes for gene: LCP2 were set to Immunodeficiency 81, MIM# 619374; Severe combined immunodeficiency
Severe Combined Immunodeficiency v1.24 Bryony Thompson Copied gene RAG2 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.24 RAG2 Bryony Thompson gene: RAG2 was added
gene: RAG2 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAG2 were set to 26996199
Phenotypes for gene: RAG2 were set to Recombinase activating gene 2 deficiency MONDO:0000573
Severe Combined Immunodeficiency v1.23 Bryony Thompson Copied gene RAG1 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.23 RAG1 Bryony Thompson gene: RAG1 was added
gene: RAG1 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAG1 were set to 26689875; 26186701
Phenotypes for gene: RAG1 were set to Recombinase activating gene 1 deficiency MONDO:0000572
Severe Combined Immunodeficiency v1.22 Bryony Thompson Copied gene RAC2 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.22 RAC2 Bryony Thompson gene: RAC2 was added
gene: RAC2 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Expert list
Mode of inheritance for gene: RAC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC2 were set to 32198141; 31919089; 31382036; 31071452; 30723080; 30654050
Phenotypes for gene: RAC2 were set to SCID; recurrent bacterial and viral infections; lymphoproliferation; neutropaenia; reticular dysgenesis; deafness
Mode of pathogenicity for gene: RAC2 was set to Other
Intellectual disability syndromic and non-syndromic v1.393 BRSK1 Zornitza Stark Marked gene: BRSK1 as ready
Intellectual disability syndromic and non-syndromic v1.393 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.261 BRSK1 Zornitza Stark Marked gene: BRSK1 as ready
Genetic Epilepsy v1.261 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.393 Zornitza Stark Copied gene BRSK1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v1.393 BRSK1 Zornitza Stark gene: BRSK1 was added
gene: BRSK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BRSK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK1 were set to 41035394
Phenotypes for gene: BRSK1 were set to Neurodevelopmental disorder, MONDO:0700092, BRSK1-related
Genetic Epilepsy v1.261 Zornitza Stark Copied gene BRSK1 from panel Mendeliome
Genetic Epilepsy v1.261 BRSK1 Zornitza Stark gene: BRSK1 was added
gene: BRSK1 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: BRSK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK1 were set to 41035394
Phenotypes for gene: BRSK1 were set to Neurodevelopmental disorder, MONDO:0700092, BRSK1-related
Mendeliome v1.3479 BRSK1 Zornitza Stark Phenotypes for gene: BRSK1 were changed from Epilepsy, MONDO:0005027, BRSK1-related to Neurodevelopmental disorder, MONDO:0700092, BRSK1-related
Mendeliome v1.3478 BRSK1 Zornitza Stark Marked gene: BRSK1 as ready
Mendeliome v1.3478 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Mendeliome v1.3478 BRSK1 Zornitza Stark Classified gene: BRSK1 as Green List (high evidence)
Mendeliome v1.3478 BRSK1 Zornitza Stark Gene: brsk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.260 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Genetic Epilepsy v1.260 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Genetic Epilepsy v1.259 GRIA1 Zornitza Stark Publications for gene: GRIA1 were set to 35675825; 38890806; 37921875
Genetic Epilepsy v1.259 GRIA1 Zornitza Stark Publications for gene: GRIA1 were set to 35675825
Genetic Epilepsy v1.258 GRIA1 Zornitza Stark Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.258 GRIA1 Zornitza Stark Mode of inheritance for gene: GRIA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.257 GRIA1 Zornitza Stark Classified gene: GRIA1 as Green List (high evidence)
Genetic Epilepsy v1.257 GRIA1 Zornitza Stark Gene: gria1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.257 GRIA1 Zornitza Stark Classified gene: GRIA1 as Green List (high evidence)
Genetic Epilepsy v1.257 GRIA1 Zornitza Stark Gene: gria1 has been classified as Green List (High Evidence).
Mendeliome v1.3477 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 31752325; 30244537; 28594066; 28645153; 33199448; 33199448
Mendeliome v1.3476 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Added comment: Additional reports for association between mono allelic variants and SCA:

PMID:39729134 (2024) reported an 11-year-old male of Indian descent with childhood-onset ataxia and severe sensorineural hearing loss. Genetic analysis identified heterozygous 3' splice site variant in the PNPT1 gene (c.2014-3 C > G).

PMID:39899068 (2025) reported a 1-year-8-month-old female proband of Brazilian descent with Spinocerebellar Ataxia 25 that presented with progressive ataxia, cerebellar atrophy, and sensory neuropathy. She was identified with a novel heterozygous truncating variant in PNPT1 (c.2068del), which she inherited from her father. Although the father was previously reported as asymptomatic, he was affected with axonal and demyelinating polyneuropathy but not ataxia upon detailed examination.

PMID:39924761 (2025) reported two unrelated families, where all individuals presented with sensory ataxic neuropathy (SAN), while some individuals developed cerebellar signs. Analysis of WGS variant data through the 100,000 Genomes Project identified two different heterozygous variants in these families. Family 1 underwent a 'quad' study and the previously reported c.2014‐3C>G variant segregated in all affected family members and was absent in all unaffected family members. Sanger sequencing confirmed segregation in two other individuals. c.2014‐3C>G is the same variant that was found in the 3-generation Australian family reported by PMID:35411967, where unaffected family members harboured the variant. A novel nonsense variant (c.2143C>T/ p.Arg715Ter) was found in both affected members of Family 2.

PMID:40757543 (2024) reported an 18-year-old male presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cognitive decline since early adolescence. The patient was identified with a heterozygous pathogenic variant c.162-1G>A in PNPT1 gene.; Changed rating: GREEN; Changed publications: 35411967, 39729134, 39899068, 39924761, 40757543
Severe Combined Immunodeficiency v1.21 Bryony Thompson Copied gene PRKDC from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.21 PRKDC Bryony Thompson gene: PRKDC was added
gene: PRKDC was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRKDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKDC were set to 19075392; 23722905
Phenotypes for gene: PRKDC were set to Immunodeficiency 26, with or without neurologic abnormalities MIM# 615966; Absent T and B cells; normal NK cells; SCID; recurrent respiratory infections; microcephaly; seizures; developmental delay
Severe Combined Immunodeficiency v1.20 Bryony Thompson Copied gene NUDCD3 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.20 NUDCD3 Bryony Thompson gene: NUDCD3 was added
gene: NUDCD3 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Literature
Mode of inheritance for gene: NUDCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD3 were set to PMID: 38787962
Phenotypes for gene: NUDCD3 were set to Severe combined immunodeficiency; omenn syndrome
Severe Combined Immunodeficiency v1.19 Bryony Thompson Copied gene NHEJ1 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.19 NHEJ1 Bryony Thompson gene: NHEJ1 was added
gene: NHEJ1 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: NHEJ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHEJ1 were set to 16439204; 16439205
Phenotypes for gene: NHEJ1 were set to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; MONDO:0012650
Severe Combined Immunodeficiency v1.18 Bryony Thompson Copied gene LIG4 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.18 LIG4 Bryony Thompson gene: LIG4 was added
gene: LIG4 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
treatable tags were added to gene: LIG4.
Mode of inheritance for gene: LIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG4 were set to 27717373; 10911993
Phenotypes for gene: LIG4 were set to LIG4 syndrome MIM# 606593; T-/B-lymphocytopaenia; Normal NK, radiation sensitivity; Microcephaly; absent/low B and T cells; low Ig; raised IgM; failure to thrive; bacterial/viral/fungal infections; hypogammaglobulinaemia; neurodevelopmental delay; microcephaly; pancytopaenia
Severe Combined Immunodeficiency v1.17 Bryony Thompson Copied gene LIG1 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.17 LIG1 Bryony Thompson gene: LIG1 was added
gene: LIG1 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Literature
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to PMID: 33025376; PMID: 36341401
Phenotypes for gene: LIG1 were set to Immunodeficiency 96, MIM# 619774
Severe Combined Immunodeficiency v1.16 Bryony Thompson Copied gene DCLRE1C from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.16 DCLRE1C Bryony Thompson gene: DCLRE1C was added
gene: DCLRE1C was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert list,Expert Review Green
Mode of inheritance for gene: DCLRE1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCLRE1C were set to 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179
Phenotypes for gene: DCLRE1C were set to Severe combined immunodeficiency due to DCLRE1C deficiency, MONDO:0011225
Severe Combined Immunodeficiency v1.15 Bryony Thompson Copied gene AK2 from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.15 AK2 Bryony Thompson gene: AK2 was added
gene: AK2 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
treatable tags were added to gene: AK2.
Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK2 were set to 19043417; 19043416; 33628209
Phenotypes for gene: AK2 were set to Reticular dysgenesis MIM# 267500; MONDO:0009973; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness
Severe Combined Immunodeficiency v1.14 Bryony Thompson Copied gene ADA from panel Severe Combined Immunodeficiency (absent T absent B cells)
Severe Combined Immunodeficiency v1.14 ADA Bryony Thompson gene: ADA was added
gene: ADA was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Expert Review Green,Melbourne Genomics Health Alliance Immunology Flagship,Victorian Clinical Genetics Services
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA were set to 3007108; 3475710; 8178821; 8227344; 2783588
Phenotypes for gene: ADA were set to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Mendeliome v1.3476 ARHGAP19 Fahaz Nazer gene: ARHGAP19 was added
gene: ARHGAP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP19 were set to 41086021
Phenotypes for gene: ARHGAP19 were set to Motor Peripheral Neuropathy; MONDO:0002316; ARHGAP19 related
Review for gene: ARHGAP19 was set to GREEN
Added comment: Biallelic LOF variants in 25 individuals from 20 unrelated families
Phenotype: motor predominant neuropathy
14/23 had assymetric lower limb involvement

Biochemical GAP assays show GAP domain variants cause loss of protein function.
RNA studies show LOF alters expression of genes linked to 3 cellular pathways, compared to controls.
iPSC-derived motor neurons show reduced ARHGAP19 expression

Models: Zebrafish, drosophila loss of function models show movement deficits.

LOF variants reported in 'GAP' domain and outside this domain with no genotype-phenotype correlation noted
Sources: Literature
Genetic Epilepsy v1.256 GRIA1 Michelle Torres reviewed gene: GRIA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38890806, 37921875; Phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3476 BRSK1 Cara Beck gene: BRSK1 was added
gene: BRSK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BRSK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK1 were set to 41035394
Phenotypes for gene: BRSK1 were set to Epilepsy, MONDO:0005027, BRSK1-related
Review for gene: BRSK1 was set to GREEN
Added comment: PMID:41035394
Six novel BRSK1 variants were identified in seven probands. Five cases were de novo, two inherited. One variant was recurrent.
All had epilepsy (generalised tonic clonic seizures, absence, focal, spasms), 2/7 GDD, 1/1 'mental developmental delay', 1/7 motor delay, 2/7 normal development.
Functional work, including in a mouse model, was consistent with loss of function mechanism and supports pathogenicity of 2 frameshift, 1 nonsense, 1 missense variant, with 2 missense not yet considered pathogenic.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.48 ASIC5 Jasmine Chew edited their review of gene: ASIC5: Changed publications: 34395479
Infertility and Recurrent Pregnancy Loss v1.48 ASIC5 Jasmine Chew gene: ASIC5 was added
gene: ASIC5 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ASIC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASIC5 were set to PMID: 34395479
Phenotypes for gene: ASIC5 were set to Unexplained recurrent pregnancy loss
Review for gene: ASIC5 was set to AMBER
Added comment: PMID: 34395479 (2021)- WGS on a family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at 9th week of pregnancy revealed a novel homozygous c.680G>T, R227I missense variant inherited from parents with heterozygous variants. Another female subject was observed with an identical heterozygous variant, who is a single daughter, and her mother experienced the unexplained RPL similar with the earlier family in the ninth week of pregnancy consecutively three times. Functional analyses of the variant supported pathogenicity- reduced protein stability and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5.
Sources: Literature
Calcium and Phosphate disorders v1.28 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 35738466; 18386070; 39837581
Calcium and Phosphate disorders v1.27 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 35738466; 18386070; 39837581
Calcium and Phosphate disorders v1.26 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 35738466; 18386070; 39837581
Deafness_IsolatedAndComplex v1.238 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.26 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 35738466; 18386070; 39837581
Deafness_IsolatedAndComplex v1.237 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 9916796; 12414817; 16611712; 18798332
Calcium and Phosphate disorders v1.25 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 35738466; 18386070
Deafness_IsolatedAndComplex v1.237 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.25 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.24 ATP6V1B1 Elena Savva reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.236 ATP6V1B1 Elena Savva reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v1.22 ATP6V1B1 Elena Savva Marked gene: ATP6V1B1 as ready
Renal Tubulopathies and related disorders v1.22 ATP6V1B1 Elena Savva Gene: atp6v1b1 has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.22 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 12414817; 9916796; 18798332; 16611712
Renal Tubulopathies and related disorders v1.21 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v1.20 ATP6V1B1 Elena Savva reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3476 ATP6V1B1 Elena Savva Publications for gene: ATP6V1B1 were set to 9916796; 12414817; 16611712; 18798332
Mendeliome v1.3475 ATP6V1B1 Elena Savva Mode of inheritance for gene: ATP6V1B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3474 ATP6V1B1 Elena Savva reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM#267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.392 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390 to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Intellectual disability syndromic and non-syndromic v1.391 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder (MONDO:0700092), KLHL20-related to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Genetic Epilepsy v1.256 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390 to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Intellectual disability syndromic and non-syndromic v1.390 KLHL20 Zornitza Stark reviewed gene: KLHL20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.256 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder (MONDO:0700092), KLHL20-related to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Genetic Epilepsy v1.255 KLHL20 Zornitza Stark reviewed gene: KLHL20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3474 KLHL20 Zornitza Stark Phenotypes for gene: KLHL20 were changed from Neurodevelopmental disorder (MONDO:0700092), KLHL20-related to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390
Mendeliome v1.3473 KLHL20 Zornitza Stark reviewed gene: KLHL20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, MIM# 621390; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Frontonasal dysplasia v1.3 KCTD15 Zornitza Stark Marked gene: KCTD15 as ready
Frontonasal dysplasia v1.3 KCTD15 Zornitza Stark Gene: kctd15 has been classified as Amber List (Moderate Evidence).
Frontonasal dysplasia v1.3 Zornitza Stark Copied gene KCTD15 from panel Mendeliome
Frontonasal dysplasia v1.3 KCTD15 Zornitza Stark gene: KCTD15 was added
gene: KCTD15 was added to Frontonasal dysplasia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: KCTD15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD15 were set to 38296633
Phenotypes for gene: KCTD15 were set to frontonasal dysplasia, MONDO:0016643
Mode of pathogenicity for gene: KCTD15 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.3473 KCTD15 Zornitza Stark Marked gene: KCTD15 as ready
Mendeliome v1.3473 KCTD15 Zornitza Stark Gene: kctd15 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3473 KCTD15 Zornitza Stark Classified gene: KCTD15 as Amber List (moderate evidence)
Mendeliome v1.3473 KCTD15 Zornitza Stark Gene: kctd15 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.400 SOX2 Zornitza Stark Publications for gene: SOX2 were set to 38553553; 39736497
Cerebral Palsy v1.399 SOX2 Zornitza Stark Publications for gene: SOX2 were set to PMID: 38553553
Cerebral Palsy v1.398 SOX2 Zornitza Stark Classified gene: SOX2 as Amber List (moderate evidence)
Cerebral Palsy v1.398 SOX2 Zornitza Stark Gene: sox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3472 OCRL Zornitza Stark Phenotypes for gene: OCRL were changed from Dent disease 2, MIM# 300555; Lowe syndrome , MIM#309000 to Oculocerebrorenal syndrome MONDO:0010645; Dent disease 2, MIM# 300555; Lowe syndrome , MIM#309000
Fetal anomalies v1.462 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Fetal anomalies v1.461 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.390 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393 to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Intellectual disability syndromic and non-syndromic v1.389 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Intellectual disability syndromic and non-syndromic v1.388 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.91 SNAPIN Zornitza Stark Marked gene: SNAPIN as ready
Cerebellar and Pontocerebellar Hypoplasia v1.91 SNAPIN Zornitza Stark Gene: snapin has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.91 Zornitza Stark Copied gene SNAPIN from panel Callosome
Cerebellar and Pontocerebellar Hypoplasia v1.91 SNAPIN Zornitza Stark gene: SNAPIN was added
gene: SNAPIN was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SNAPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAPIN were set to 40930097; 26539891
Phenotypes for gene: SNAPIN were set to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Callosome v0.565 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393 to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Callosome v0.564 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Callosome v0.563 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.351 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393 to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Microcephaly v1.350 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Microcephaly v1.349 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3471 SNAPIN Zornitza Stark Phenotypes for gene: SNAPIN were changed from Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related to Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393
Mendeliome v1.3470 SNAPIN Zornitza Stark reviewed gene: SNAPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, MIM# 621393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.388 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from Molybdenum cofactor deficiency, type B2, MIM# 621373 to Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3470 IFNGR2 Zornitza Stark Publications for gene: IFNGR2 were set to 15924140; 18625743; 31222290
Mendeliome v1.3469 IFNGR2 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported with bi-allelic disease.
Mendeliome v1.3469 IFNGR2 Zornitza Stark edited their review of gene: IFNGR2: Added comment: PMID 23161749: single case report of heterozygous LoF variant causing disease (but ?missed second hit).; Changed publications: 15924140, 18625743, 31222290, 23161749
Clefting disorders v0.277 LOXL3 Zornitza Stark Marked gene: LOXL3 as ready
Clefting disorders v0.277 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Clefting disorders v0.277 Zornitza Stark Copied gene LOXL3 from panel Pierre Robin Sequence
Clefting disorders v0.277 LOXL3 Zornitza Stark gene: LOXL3 was added
gene: LOXL3 was added to Clefting disorders. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXL3 were set to 25663169; 26307084; 26957899; 29802726; 30362103; 34787502; 41052910
Phenotypes for gene: LOXL3 were set to Stickler syndrome, MONDO:0019354, LOXL3-related
Pierre Robin Sequence v0.53 LOXL3 Zornitza Stark Marked gene: LOXL3 as ready
Pierre Robin Sequence v0.53 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Pierre Robin Sequence v0.53 Zornitza Stark Copied gene LOXL3 from panel Fetal anomalies
Pierre Robin Sequence v0.53 LOXL3 Zornitza Stark gene: LOXL3 was added
gene: LOXL3 was added to Pierre Robin Sequence. Sources: Expert Review Green,Literature
Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXL3 were set to 25663169; 26307084; 26957899; 29802726; 30362103; 34787502; 41052910
Phenotypes for gene: LOXL3 were set to Stickler syndrome, MONDO:0019354, LOXL3-related
Fetal anomalies v1.461 LOXL3 Zornitza Stark Phenotypes for gene: LOXL3 were changed from Stickler syndrome; cleft lip/palate to Stickler syndrome, MONDO:0019354, LOXL3-related
Fetal anomalies v1.460 LOXL3 Zornitza Stark Publications for gene: LOXL3 were set to 25663169; 26307084; 26957899; 29802726; 30362103; 34787502
Fetal anomalies v1.459 LOXL3 Zornitza Stark Classified gene: LOXL3 as Green List (high evidence)
Fetal anomalies v1.459 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Fetal anomalies v1.458 LOXL3 Zornitza Stark reviewed gene: LOXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 41052910; Phenotypes: Stickler syndrome, MONDO:0019354, LOXL3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Stickler Syndrome v1.12 LOXL3 Zornitza Stark Phenotypes for gene: LOXL3 were changed from Stickler syndrome to Stickler syndrome, MONDO:0019354, LOXL3-related
Stickler Syndrome v1.11 LOXL3 Zornitza Stark Classified gene: LOXL3 as Green List (high evidence)
Stickler Syndrome v1.11 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Stickler Syndrome v1.10 LOXL3 Zornitza Stark edited their review of gene: LOXL3: Added comment: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease. Zebrafish model also available.; Changed rating: GREEN; Changed publications: 30362103, 25663169, 41052910; Changed phenotypes: Stickler syndrome, MONDO:0019354, LOXL3-related
Mendeliome v1.3469 LOXL3 Zornitza Stark Phenotypes for gene: LOXL3 were changed from Stickler syndrome to Stickler syndrome, MONDO:0019354, LOXL3-related
Mendeliome v1.3468 LOXL3 Zornitza Stark Publications for gene: LOXL3 were set to 30362103; 25663169
Mendeliome v1.3467 LOXL3 Zornitza Stark Classified gene: LOXL3 as Green List (high evidence)
Mendeliome v1.3467 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Green List (High Evidence).
Mendeliome v1.3466 LOXL3 Zornitza Stark changed review comment from: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease.; to: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease. Zebrafish model also available.
Mendeliome v1.3466 LOXL3 Zornitza Stark edited their review of gene: LOXL3: Added comment: PMID 41052910: additional family reported, three affected sibs, compound het variants segregated with disease.; Changed rating: GREEN; Changed publications: 30362103, 25663169, 41052910; Changed phenotypes: Stickler syndrome, MONDO:0019354, LOXL3-related
Mendeliome v1.3466 CDKL1 Zornitza Stark Classified gene: CDKL1 as Red List (low evidence)
Mendeliome v1.3466 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Mendeliome v1.3465 CDKL1 Zornitza Stark Deleted their comment
Mendeliome v1.3465 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Changed rating: RED
Intellectual disability syndromic and non-syndromic v1.387 CDKL1 Zornitza Stark Classified gene: CDKL1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.387 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.386 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Changed rating: RED
Intellectual disability syndromic and non-syndromic v1.386 CDKL1 Zornitza Stark Deleted their comment
Mendeliome v1.3465 CDKL1 Zornitza Stark Classified gene: CDKL1 as Amber List (moderate evidence)
Mendeliome v1.3465 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3464 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Added comment: PMID 40088891 reports two unrelated individuals with de novo heterozygous CDKL1 missense variants (p.Val115Ala, p.Arg169Cys) presenting with childhood‑onset neurodevelopmental disorder, developmental delay and seizures; Drosophila rescue assays show dominant‑negative activity of the variants. However, note that the variants are present at low frequency in gnomAD v4, p.Val115Ala: 2 individuals, p.Arg169Cys: 13 individuals. Some supportive functional data presented. Upgrade to Amber but not Green due to pop counts.; Changed rating: AMBER; Changed publications: 40088891
Intellectual disability syndromic and non-syndromic v1.386 CDKL1 Zornitza Stark Mode of pathogenicity for gene: CDKL1 was changed from None to None
Intellectual disability syndromic and non-syndromic v1.386 CDKL1 Zornitza Stark Mode of pathogenicity for gene: CDKL1 was changed from Other to None
Intellectual disability syndromic and non-syndromic v1.385 CDKL1 Zornitza Stark Classified gene: CDKL1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.385 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.384 CDKL1 Zornitza Stark edited their review of gene: CDKL1: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v1.384 CDKL1 Zornitza Stark commented on gene: CDKL1: PMID 40088891 reports two unrelated individuals with de novo heterozygous CDKL1 missense variants (p.Val115Ala, p.Arg169Cys) presenting with childhood‑onset neurodevelopmental disorder, developmental delay and seizures; Drosophila rescue assays show dominant‑negative activity of the variants. However, note that the variants are present at low frequency in gnomAD v4, p.Val115Ala: 2 individuals, p.Arg169Cys: 13 individuals. Some supportive functional data presented. Upgrade to Amber but not Green due to pop counts.
Mendeliome v1.3464 TEKT3 Zornitza Stark Marked gene: TEKT3 as ready
Mendeliome v1.3464 TEKT3 Zornitza Stark Gene: tekt3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3464 Zornitza Stark Copied gene TEKT3 from panel Infertility and Recurrent Pregnancy Loss
Mendeliome v1.3464 TEKT3 Zornitza Stark gene: TEKT3 was added
gene: TEKT3 was added to Mendeliome. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: TEKT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEKT3 were set to 36708031
Phenotypes for gene: TEKT3 were set to Spermatogenic failure, MONDO:0004983, TEKT3-related
Infertility and Recurrent Pregnancy Loss v1.48 TEKT3 Zornitza Stark Marked gene: TEKT3 as ready
Infertility and Recurrent Pregnancy Loss v1.48 TEKT3 Zornitza Stark Gene: tekt3 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.48 TEKT3 Zornitza Stark Classified gene: TEKT3 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.48 TEKT3 Zornitza Stark Gene: tekt3 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.47 TEKT3 Zornitza Stark gene: TEKT3 was added
gene: TEKT3 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TEKT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEKT3 were set to 36708031
Phenotypes for gene: TEKT3 were set to Spermatogenic failure, MONDO:0004983, TEKT3-related
Review for gene: TEKT3 was set to AMBER
Added comment: PMID: 36708031 reports two unrelated families with biallelic TEKT3 l variants causing oligoasthenoteratozoospermia and male infertility, some supportive functional data.
Sources: Literature
Mendeliome v1.3463 OCRL Sangavi Sivagnanasundram reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 1321346; Phenotypes: oculocerebrorenal syndrome MONDO:0010645; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.360 VPS13A Zornitza Stark Marked gene: VPS13A as ready
Incidentalome v0.360 VPS13A Zornitza Stark Gene: vps13a has been classified as Green List (High Evidence).
Incidentalome v0.360 VPS13A Zornitza Stark Phenotypes for gene: VPS13A were changed from Choreoacanthocytosis MIM#200150 to Choreoacanthocytosis MIM#200150
Incidentalome v0.360 VPS13A Zornitza Stark Phenotypes for gene: VPS13A were changed from to Choreoacanthocytosis MIM#200150
Mendeliome v1.3463 NUS1 Sangavi Sivagnanasundram reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083; Phenotypes: progressive myoclonus epilepsy MONDO:0020074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.359 VPS13A Zornitza Stark Publications for gene: VPS13A were set to 26813249; 15824261; 30140251; 31192303
Incidentalome v0.359 VPS13A Zornitza Stark Publications for gene: VPS13A were set to
Incidentalome v0.358 VPS13A Zornitza Stark Mode of inheritance for gene: VPS13A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.50 TH Zornitza Stark Phenotypes for gene: TH were changed from Segawa syndrome, recessive MIM#605407 to Segawa syndrome, recessive MIM#605407
Early-onset Dementia v1.50 TH Zornitza Stark Marked gene: TH as ready
Early-onset Dementia v1.50 TH Zornitza Stark Gene: th has been classified as Red List (Low Evidence).
Early-onset Dementia v1.50 TH Zornitza Stark Phenotypes for gene: TH were changed from to Segawa syndrome, recessive MIM#605407
Early-onset Dementia v1.49 TH Zornitza Stark Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.357 PTEN Zornitza Stark Marked gene: PTEN as ready
Incidentalome v0.357 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Incidentalome v0.357 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Cowden syndrome 1, MIM# 158350
Incidentalome v0.357 PTEN Zornitza Stark Publications for gene: PTEN were set to 32588888
Incidentalome v0.356 PTEN Zornitza Stark Publications for gene: PTEN were set to
Incidentalome v0.355 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.354 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.353 NOTCH3 Zornitza Stark Marked gene: NOTCH3 as ready
Incidentalome v0.353 NOTCH3 Zornitza Stark Gene: notch3 has been classified as Green List (High Evidence).
Incidentalome v0.353 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 125310 to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 125310
Incidentalome v0.352 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 125310
Incidentalome v0.352 NOTCH3 Zornitza Stark Publications for gene: NOTCH3 were set to 31960911
Incidentalome v0.351 NOTCH3 Zornitza Stark Publications for gene: NOTCH3 were set to
Incidentalome v0.350 NOTCH3 Zornitza Stark Mode of inheritance for gene: NOTCH3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3463 NLRP2 Zornitza Stark Phenotypes for gene: NLRP2 were changed from female infertility; early embryonic arrest to Oocyte/zygote/embryo maturation arrest 18, MONDO:0957230
Mendeliome v1.3462 NLRP2 Zornitza Stark Publications for gene: NLRP2 were set to 30877238; 19300480; 29574422; 33090377
Mendeliome v1.3461 NLRP2 Zornitza Stark Mode of inheritance for gene: NLRP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3460 NLRP2 Zornitza Stark edited their review of gene: NLRP2: Added comment: PMIDs 29574422, 30877238, 35643636, 39887367 and 41044650 report 15 unrelated families with rare NLRP2 variants. Maternal heterozygous variants cause multilocus imprinting disturbance (MLID) presenting as Beckwith‑Wiedemann syndrome, Silver‑Russell syndrome, transient neonatal diabetes mellitus, unspecified imprinting disorder and pseudohypoparathyroidism type‑1B. Biallelic loss‑of‑function variants cause autosomal recessive primary female infertility with early embryonic arrest (embryos arresting at the 2–4‑cell stage). Functional studies show reduced NLRP2 protein in patient‑derived cells and mouse Nlrp2 knockout recapitulating the embryonic arrest phenotype. No contradictory evidence exists for the well‑supported phenotypes.; Changed publications: 29574422, 30877238, 35643636, 39887367, 41044650
Mendeliome v1.3460 NLRP2 Zornitza Stark reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.3460 MVK Zornitza Stark Phenotypes for gene: MVK were changed from Mevalonic aciduria MIM# 610377 to Mevalonic aciduria MIM#610377; Porokeratosis 3, multiple types, MIM# 175900
Mendeliome v1.3459 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3458 MVK Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease associations.
Mendeliome v1.3458 MVK Zornitza Stark edited their review of gene: MVK: Changed phenotypes: Mevalonic aciduria MIM#610377, Porokeratosis 3, multiple types, MIM# 175900; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3458 LBR Zornitza Stark Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia, MIM# 215140 to Greenberg skeletal dysplasia, MIM#215140; Pelger-Huet anomaly, MIM# 169400
Mendeliome v1.3457 LBR Zornitza Stark Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3456 LBR Zornitza Stark changed review comment from: Overlap with ATD in particular.
Sources: Expert list; to: Well established mono- and biallelic gene-disease associations.
Sources: Expert list
Mendeliome v1.3456 LBR Zornitza Stark edited their review of gene: LBR: Changed phenotypes: Greenberg skeletal dysplasia, MIM#215140, Pelger-Huet anomaly, MIM# 169400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cholestasis v1.5 GBA Zornitza Stark Tag new gene name tag was added to gene: GBA.
Early-onset Parkinson disease v2.43 GBA Zornitza Stark Tag new gene name tag was added to gene: GBA.
Incidentalome v0.349 GBA Zornitza Stark Tag new gene name tag was added to gene: GBA.
Infertility and Recurrent Pregnancy Loss v1.46 CFAP206 Zornitza Stark Marked gene: CFAP206 as ready
Infertility and Recurrent Pregnancy Loss v1.46 CFAP206 Zornitza Stark Gene: cfap206 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.46 Zornitza Stark Copied gene CFAP206 from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v1.46 CFAP206 Zornitza Stark gene: CFAP206 was added
gene: CFAP206 was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CFAP206 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP206 were set to 34255152
Phenotypes for gene: CFAP206 were set to Spermatogenic failure 102, MIM# 621387
Penetrance for gene: CFAP206 were set to unknown
Mendeliome v1.3456 CFAP206 Zornitza Stark Phenotypes for gene: CFAP206 were changed from Multiple morphological abnormalities of the flagella to Spermatogenic failure 102, MIM# 621387
Mendeliome v1.3455 CFAP206 Zornitza Stark reviewed gene: CFAP206: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 102, MIM# 621387; Mode of inheritance: None
Liver Failure_Paediatric v1.30 Chirag Patel Copied gene ASL from panel Hyperammonaemia
Liver Failure_Paediatric v1.30 ASL Chirag Patel gene: ASL was added
gene: ASL was added to Liver Failure_Paediatric. Sources: Expert Review Green,Expert Review Green,Genomics England PanelApp,NHS GMS,Expert list,Victorian Clinical Genetics Services
treatable tags were added to gene: ASL.
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 2263616; 12408190
Phenotypes for gene: ASL were set to Argininosuccinic aciduria 207900
Cerebral Palsy v1.397 SOX2 Clare van Eyk edited their review of gene: SOX2: Added comment: Additional report of a 12 year old girl with a spastic and dystonic movement disorder diagnosed as CP and found to have a de novo loss of function variant in SOX2 (same child reported in both PMID: 39736497; https://doi.org/10.1186/s43042-025-00665-z). Notably, she did not have ocular symptoms.; Changed rating: AMBER; Changed publications: PMID: 38553553, PMID: 39736497
Kidney Cancer v1.2 SDHAF2 Chirag Patel Classified gene: SDHAF2 as Red List (low evidence)
Kidney Cancer v1.2 SDHAF2 Chirag Patel Gene: sdhaf2 has been classified as Red List (Low Evidence).
Kidney Cancer v1.1 SDHAF2 Chirag Patel Deleted their comment
Kidney Cancer v1.1 SDHAF2 Chirag Patel changed review comment from: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review; to: ClinGen definitive for HPP.
Renal carcinoma reported in HPP but no evidence in SDHAF2-related HPP.
Sources: Expert list, Expert Review
Kidney Cancer v1.1 SDHAF2 Chirag Patel edited their review of gene: SDHAF2: Added comment: evidence of renal cancers in SDHAF2-related HPP; Changed rating: RED
Genomic newborn screening: ICoNS v0.16 GLA Abigail Veldman gene: GLA was added
gene: GLA was added to Genomic newborn screening: ICoNS. Sources: ClinGen,Literature
Mode of inheritance for gene: GLA 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: GLA were set to 28613767; 37259462
Phenotypes for gene: GLA were set to Fabry disease (MIM 301500); Fabry disease, cardiac variant (MIM 301500)
Penetrance for gene: GLA were set to Complete
Mode of pathogenicity for gene: GLA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Age of onset: Variable,
Classic form 4-8 yrs, late-onset variants >25 yrs
Specifically difficult to predict in females

Treatment:
- Agalsidase-β (Recombinant α-GAL)
- Agalsidase-α (Recombinant α-GAL)
- Migalastat (Binds reversibly to the active site of the amenable mutant of α-GAL)
- Investigational therapies

Effect of (early) treatment:
There is no consensus when to start with ERT

Penetrance:

Prevalence: Prevalence in white male populations has been linked to Fabry disease in a wide range, approximately 1:17,000 to 1:117,000. Classic Fabry disease mutations are seen in approximately 1:22,000 to 1:40,000 males, and atypical presentations are associated with about 1:1000 to 1:3000 males and 1:6000 to 1:40,000 females. Although it is an under-diagnosed condition, the disease is seen in all racial and ethnic groups. (PMID: 28613767)
Sources: ClinGen, Literature
Intellectual disability syndromic and non-syndromic v1.384 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from Molybdenum cofactor deficiency, type B2, MIM# 621373 to Molybdenum cofactor deficiency, type B2, MIM# 621373
Intellectual disability syndromic and non-syndromic v1.383 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from Molybdenum cofactor deficiency MONDO:0020480 to Molybdenum cofactor deficiency, type B2, MIM# 621373
Intellectual disability syndromic and non-syndromic v1.382 MOCS3 Zornitza Stark edited their review of gene: MOCS3: Changed phenotypes: Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3455 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from Molybdenum cofactor deficiency MONDO:0020480 to Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3454 MOCS3 Zornitza Stark edited their review of gene: MOCS3: Changed phenotypes: Molybdenum cofactor deficiency, type B2, MIM# 621373
Mendeliome v1.3454 NRL Zornitza Stark Phenotypes for gene: NRL were changed from Retinitis pigmentosa 27 - MIM#613750; Retinal degeneration, autosomal recessive, clumped pigment type to Retinitis pigmentosa 27 - MIM#613750; Enhanced S-cone syndrome 2, MIM# 621371
Mendeliome v1.3453 NRL Zornitza Stark reviewed gene: NRL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Enhanced S-cone syndrome 2, MIM# 621371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.182 NRL Zornitza Stark Marked gene: NRL as ready
Retinitis pigmentosa v0.182 NRL Zornitza Stark Gene: nrl has been classified as Green List (High Evidence).
Retinitis pigmentosa v0.182 NRL Zornitza Stark Phenotypes for gene: NRL were changed from Retinitis pigmentosa 27 (AD); Retinal degeneration, autosomal recessive, clumped pigment type (AR) to Enhanced S-cone syndrome 2, MIM# 621371
Retinitis pigmentosa v0.181 NRL Zornitza Stark Publications for gene: NRL were set to
Retinitis pigmentosa v0.180 NRL Zornitza Stark edited their review of gene: NRL: Changed publications: 39766861, 36140584, 35693422
Retinitis pigmentosa v0.180 NRL Zornitza Stark edited their review of gene: NRL: Added comment: More than 5 families reported with the recessive phenotype.; Changed publications: 39766861
Retinitis pigmentosa v0.180 NRL Zornitza Stark Mode of inheritance for gene: NRL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v0.179 NRL Zornitza Stark reviewed gene: NRL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Enhanced S-cone syndrome 2, MIM# 621371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Marked gene: SRRM2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.92 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.91 SRRM2 Zornitza Stark gene: SRRM2 was added
gene: SRRM2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 40967764
Phenotypes for gene: SRRM2 were set to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Review for gene: SRRM2 was set to GREEN
Added comment: Four de novo loss-of-function (LoF) variants in SRRM2 were identified in 4 out of 71 patients with persistent tachypnoea of infancy, suggesting this is part of the phenotypic spectrum for this condition. All four had mild DD/ID.
Sources: Literature
Mendeliome v1.3453 KCTD15 Achchuthan Shanmugasundram gene: KCTD15 was added
gene: KCTD15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCTD15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD15 were set to 38296633
Phenotypes for gene: KCTD15 were set to frontonasal dysplasia, MONDO:0016643
Mode of pathogenicity for gene: KCTD15 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KCTD15 was set to AMBER
Added comment: PMID:38296633 (2024) reported a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in the affected father and daughter via exome sequencing and the variant segregated with the phenotype. A de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was identified via targeted DNA sequencing in a similarly affected sporadic patient.

There is some functional evidence available from structural analyses, which demonstrated that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.
Sources: Literature
Mendeliome v1.3453 RIPOR2 Arina Puzriakova edited their review of gene: RIPOR2: Added comment: PMID: 37864412 - a distinct homozygous LOF variant (c.1561C>T (p.Arg521*)) in exon 14 of the RIPOR2 gene was identified by WES in three siblings from a consanguineous Tunisian family with non-syndromic bilateral profound hearing and vestibular dysfunctions. Parents were unaffected heterozygous carriers. No other variants in hearing loss genes were found. Zebrafish model with a stop codon inserted within ripor2 exon 14 showed that F2 larva did not exhibit a different hearing or balance behaviour compared to wild-type.; Changed publications: 24958875, 32631815, 37864412; Changed phenotypes: Deafness, autosomal dominant 21, OMIM:607017, Deafness, autosomal recessive 104, OMIM:616515; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v1.255 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461 to Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461
Genetic Epilepsy v1.255 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461 to Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461
Mendeliome v1.3453 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461 to Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461
Mendeliome v1.3452 EXT2 Zornitza Stark Phenotypes for gene: EXT2 were changed from Seizures, scoliosis, and macrocephaly syndrome, MIM#616682 to Exostoses, multiple, type 2 MIM#133701; Seizures, scoliosis, and macrocephaly syndrome, MIM#616682
Mendeliome v1.3451 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v1.3450 NLRC4 Zornitza Stark Phenotypes for gene: NLRC4 were changed from Familial cold autoinflammatory syndrome 4 - MIM#616115; Autoinflammation with infantile enterocolitis - MIM#616050 to periodic fever-infantile enterocolitis-autoinflammatory syndrome MONDO:0014472
Mendeliome v1.3449 NMNAT1 Zornitza Stark Phenotypes for gene: NMNAT1 were changed from Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260; Leber congenital amaurosis 9, MIM# 608553 to NMNAT1-related retinopathy MONDO:0800101; Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260; Leber congenital amaurosis 9, MIM# 608553
Genomic newborn screening: BabyScreen+ v1.140 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) to NOG-related symphalangism spectrum disorder MONDO:0100521
Genomic newborn screening: BabyScreen+ v1.139 NOG Zornitza Stark edited their review of gene: NOG: Changed phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521
Fetal anomalies v1.458 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Brachydactyly, type B2 (MIM#611377); Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) to NOG-related symphalangism spectrum disorder MONDO:0100521
Fetal anomalies v1.457 NOG Zornitza Stark reviewed gene: NOG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.78 NOG Zornitza Stark Marked gene: NOG as ready
Hand and foot malformations v0.78 NOG Zornitza Stark Gene: nog has been classified as Green List (High Evidence).
Hand and foot malformations v0.78 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Stapes ankylosis with broad thumb and toes 184460; Symphalangism, proximal, 1A 185800; Multiple synostoses syndrome 1 186500; Tarsal-carpal coalition syndrome 186570; Brachydactyly, type B2 611377 to NOG-related symphalangism spectrum disorder MONDO:0100521
Hand and foot malformations v0.77 NOG Zornitza Stark reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.346 NOG Zornitza Stark Phenotypes for gene: NOG were changed from NOG-related symphalangism spectrum disorder MONDO:0100521 to NOG-related symphalangism spectrum disorder MONDO:0100521
Skeletal dysplasia v0.345 NOG Zornitza Stark Marked gene: NOG as ready
Skeletal dysplasia v0.345 NOG Zornitza Stark Gene: nog has been classified as Green List (High Evidence).
Skeletal dysplasia v0.345 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Tarsal-carpal coalition syndrome 186570; Stapes ankylosis with broad thumb and toes 184460; Brachydactyly, type B2 611377; Symphalangism, proximal, 1A 185800; Multiple synostoses syndrome 1 186500 to NOG-related symphalangism spectrum disorder MONDO:0100521
Skeletal dysplasia v0.344 NOG Zornitza Stark Publications for gene: NOG were set to
Skeletal dysplasia v0.343 NOG Zornitza Stark reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3448 NOG Zornitza Stark Phenotypes for gene: NOG were changed from Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) to NOG-related symphalangism spectrum disorder MONDO:0100521
Mendeliome v1.3447 NPHP3 Sangavi Sivagnanasundram reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872122, 19177160; Phenotypes: Nephronophthisis MONDO:0019005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3447 NPHP1 Sangavi Sivagnanasundram reviewed gene: NPHP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 1 MONDO:0009728; Mode of inheritance: None
Mendeliome v1.3447 NOTCH2 Sangavi Sivagnanasundram reviewed gene: NOTCH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acroosteolysis dominant type MONDO:0007057, Alagille syndrome MONDO:0007318; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3447 NOG Sangavi Sivagnanasundram reviewed gene: NOG: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NOG-related symphalangism spectrum disorder MONDO:0100521; Mode of inheritance: None
Mendeliome v1.3447 NMNAT1 Sangavi Sivagnanasundram reviewed gene: NMNAT1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: NMNAT1-related retinopathy MONDO:0800101; Mode of inheritance: None
Mendeliome v1.3447 NLRC4 Sangavi Sivagnanasundram reviewed gene: NLRC4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: periodic fever-infantile enterocolitis-autoinflammatory syndrome MONDO:0014472; Mode of inheritance: None
Mendeliome v1.3447 NKX2-1 Sangavi Sivagnanasundram edited their review of gene: NKX2-1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3447 NKX2-1 Sangavi Sivagnanasundram reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, MONDO:0100520; Mode of inheritance: None
Hereditary Spastic Paraplegia v1.102 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382
Hereditary Spastic Paraplegia v1.101 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.333 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382
Leukodystrophy - paediatric v0.332 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.382 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382
Intellectual disability syndromic and non-syndromic v1.381 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.563 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382
Callosome v0.562 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioural abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3447 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382
Mendeliome v1.3446 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.224 TBCB Zornitza Stark Phenotypes for gene: TBCB were changed from Neurodevelopmental disorder, MONDO:0700092, TBCB-related to Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382
Autism v0.223 TBCB Zornitza Stark reviewed gene: TBCB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia, MIM# 621382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Stroke v1.28 ABCC6 Elena Savva Mode of inheritance for gene: ABCC6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3446 SETD5 Zornitza Stark edited their review of gene: SETD5: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.381 KMT2B Zornitza Stark commented on gene: KMT2B: Note ClinGen have lumped the dystonia and ID phenotypes as these overlap in the same families. Association considered DEFINITIVE.
Mendeliome v1.3446 FSHR Lucy Spencer reviewed gene: FSHR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian dysgenesis 1 MIM#233300, Ovarian hyperstimulation syndrome MIM#608115; Mode of inheritance: None
Mendeliome v1.3446 FOXE3 Lucy Spencer commented on gene: FOXE3
Mendeliome v1.3446 EXT2 Lucy Spencer reviewed gene: EXT2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Exostoses, multiple, type 2 MIM#133701; Mode of inheritance: None
Mendeliome v1.3446 RNH1 Lucy Spencer reviewed gene: RNH1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, acute, infection-induced, susceptibility to, 12 MIM#620461; Mode of inheritance: None
Mendeliome v1.3446 RMI2 Lucy Spencer reviewed gene: RMI2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Bloom syndrome MONDO:0008876, RMI2-related; Mode of inheritance: None
Mendeliome v1.3446 RLBP1 Lucy Spencer reviewed gene: RLBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: RLBP1-related retinopathy MONDO:0100444; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3446 RIPK1 Lucy Spencer reviewed gene: RIPK1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammation with episodic fever and lymphadenopathy MIM#618852; Mode of inheritance: None
Mendeliome v1.3446 RING1 Lucy Spencer reviewed gene: RING1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RING1-related; Mode of inheritance: None
Mendeliome v1.3446 RIMS1 Lucy Spencer reviewed gene: RIMS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy MONDO:0015993, RIMS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3446 RHOH Lucy Spencer reviewed gene: RHOH: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 129 MIM#618307; Mode of inheritance: None
Mendeliome v1.3446 TBX2 Zornitza Stark Marked gene: TBX2 as ready
Mendeliome v1.3446 TBX2 Zornitza Stark Added comment: Comment when marking as ready: Green for the association with skeletal disorder, Amber for association with deafness.
Mendeliome v1.3446 TBX2 Zornitza Stark Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3446 TBX2 Zornitza Stark Phenotypes for gene: TBX2 were changed from Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223 to Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223; Hearing loss disorder, MONDO:0005365, TBX2-related
Mendeliome v1.3445 TBX2 Zornitza Stark Classified gene: TBX2 as Green List (high evidence)
Mendeliome v1.3445 TBX2 Zornitza Stark Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3444 TBX2 Zornitza Stark Classified gene: TBX2 as Amber List (moderate evidence)
Mendeliome v1.3444 TBX2 Zornitza Stark Gene: tbx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.381 TBX2 Krithika Murali Classified gene: TBX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.381 TBX2 Krithika Murali Gene: tbx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.380 TBX2 Krithika Murali Marked gene: TBX2 as ready
Intellectual disability syndromic and non-syndromic v1.380 TBX2 Krithika Murali Gene: tbx2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.380 TBX2 Krithika Murali gene: TBX2 was added
gene: TBX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TBX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX2 were set to PMID: 36733940
Phenotypes for gene: TBX2 were set to Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223
Review for gene: TBX2 was set to AMBER
Added comment: PMID: 36733940 Rafeeq et al 2022 report a novel de novo nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in a child with chondrodysplasia. Skeletal features included spinal deformities, short limbs, metaphyseal and epiphyseal dysplasia, and bilateral developmental dislocation of the hip (DDH).

Global developmental delay was also noted in this child.
Sources: Literature
Skeletal dysplasia v0.343 TBX2 Krithika Murali Classified gene: TBX2 as Green List (high evidence)
Skeletal dysplasia v0.343 TBX2 Krithika Murali Gene: tbx2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.342 TBX2 Krithika Murali Marked gene: TBX2 as ready
Skeletal dysplasia v0.342 TBX2 Krithika Murali Gene: tbx2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.342 TBX2 Krithika Murali gene: TBX2 was added
gene: TBX2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TBX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX2 were set to 29726930; 23727221; 20635360; 30223900; 36733940; 35311234
Phenotypes for gene: TBX2 were set to Vertebral anomalies and variable endocrine and T-cell dysfunction - MIM#618223
Review for gene: TBX2 was set to GREEN
Added comment: Skeletal anomalies are part of the phenotypic spectrum.
Sources: Literature
Mendeliome v1.3443 TBX2 Krithika Murali Classified gene: TBX2 as Green List (high evidence)
Mendeliome v1.3443 TBX2 Krithika Murali Gene: tbx2 has been classified as Green List (High Evidence).
Mendeliome v1.3442 TBX2 Krithika Murali edited their review of gene: TBX2: Added comment: PMID: 36733940 Rafeeq et al 2022 report a novel de novo nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in a child with chondrodysplasia and GDD. Skeletal features included spinal deformities, short limbs, metaphyseal and epiphyseal dysplasia, and bilateral developmental dislocation of the hip (DDH).

PMID: 35311234 Makitie et al 2022 report a three-generation Finnish family with autosomal dominant osteochondrodysplasia and empty sella. Affected individuals (age range 24-44 years) exhibited unusual codfish-shaped vertebrae, severe early-onset and debilitating osteoarthritis and an empty sella without endocrine abnormalities. Clinical characteristics also include mild dysmorphic features, reduced sitting height ratio, and obesity.; Changed rating: GREEN
Leukodystrophy - paediatric v0.332 SLC7A2 Zornitza Stark Marked gene: SLC7A2 as ready
Leukodystrophy - paediatric v0.332 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.332 SLC7A2 Zornitza Stark Classified gene: SLC7A2 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.332 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.331 SLC7A2 Zornitza Stark gene: SLC7A2 was added
gene: SLC7A2 was added to Leukodystrophy - paediatric. Sources: Literature
founder tags were added to gene: SLC7A2.
Mode of inheritance for gene: SLC7A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A2 were set to 41015522
Phenotypes for gene: SLC7A2 were set to Leukodystrophy, MONDO:0019046, SLC7A2-related
Review for gene: SLC7A2 was set to AMBER
Added comment: RAVINE leukoencephalopathy (RLE) is a hereditary autosomal recessive disease characterized by typical clinical and radiological signs that has so far been observed only in patients of Reunionese origin. The term RAVINE is a French acronym for the main clinical features of the disease: Réunion, Anorexie, Vomissements Incoercibles, signes NEurologiques (Reunion, Anorexia, Intractable Vomiting, NEurological signs). Patients with RLE carry the IVS1-1778A>G mutation of the SLC7A2 gene in the homozygous state. Onset is in infancy. Death typically occurs before the age of 28months in a very narrow time window (23.0±2.2months).

PMID 41015522 summarises data from 40 affected individuals.
Sources: Literature
Regression v0.590 SLC7A2 Zornitza Stark Marked gene: SLC7A2 as ready
Regression v0.590 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Regression v0.590 SLC7A2 Zornitza Stark Classified gene: SLC7A2 as Amber List (moderate evidence)
Regression v0.590 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Regression v0.589 SLC7A2 Zornitza Stark gene: SLC7A2 was added
gene: SLC7A2 was added to Regression. Sources: Literature
founder tags were added to gene: SLC7A2.
Mode of inheritance for gene: SLC7A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A2 were set to 41015522
Phenotypes for gene: SLC7A2 were set to Leukodystrophy, MONDO:0019046, SLC7A2-related
Review for gene: SLC7A2 was set to AMBER
Added comment: RAVINE leukoencephalopathy (RLE) is a hereditary autosomal recessive disease characterized by typical clinical and radiological signs that has so far been observed only in patients of Reunionese origin. The term RAVINE is a French acronym for the main clinical features of the disease: Réunion, Anorexie, Vomissements Incoercibles, signes NEurologiques (Reunion, Anorexia, Intractable Vomiting, NEurological signs). Patients with RLE carry the IVS1-1778A>G mutation of the SLC7A2 gene in the homozygous state. Onset is in infancy. Death typically occurs before the age of 28months in a very narrow time window (23.0±2.2months).

PMID 41015522 summarises data from 40 affected individuals.
Sources: Literature
Mendeliome v1.3442 SLC7A2 Zornitza Stark Marked gene: SLC7A2 as ready
Mendeliome v1.3442 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3442 SLC7A2 Zornitza Stark Classified gene: SLC7A2 as Amber List (moderate evidence)
Mendeliome v1.3442 SLC7A2 Zornitza Stark Gene: slc7a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3441 SLC7A2 Zornitza Stark gene: SLC7A2 was added
gene: SLC7A2 was added to Mendeliome. Sources: Literature
founder tags were added to gene: SLC7A2.
Mode of inheritance for gene: SLC7A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A2 were set to 41015522
Phenotypes for gene: SLC7A2 were set to Leukodystrophy, MONDO:0019046, SLC7A2-related
Review for gene: SLC7A2 was set to AMBER
Added comment: RAVINE leukoencephalopathy (RLE) is a hereditary autosomal recessive disease characterized by typical clinical and radiological signs that has so far been observed only in patients of Reunionese origin. The term RAVINE is a French acronym for the main clinical features of the disease: Réunion, Anorexie, Vomissements Incoercibles, signes NEurologiques (Reunion, Anorexia, Intractable Vomiting, NEurological signs). Patients with RLE carry the IVS1-1778A>G mutation of the SLC7A2 gene in the homozygous state.

Onset is in infancy. Death typically occurs before the age of 28months in a very narrow time window (23.0±2.2months).

PMID 41015522 summarises data from 40 affected individuals.
Sources: Literature
Fetal anomalies v1.457 AMOT Zornitza Stark Marked gene: AMOT as ready
Fetal anomalies v1.457 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Fetal anomalies v1.457 AMOT Zornitza Stark Classified gene: AMOT as Red List (low evidence)
Fetal anomalies v1.457 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Fetal anomalies v1.456 AMOT Zornitza Stark reviewed gene: AMOT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hydrocephalus_Ventriculomegaly v0.132 AMOT Zornitza Stark Marked gene: AMOT as ready
Hydrocephalus_Ventriculomegaly v0.132 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.132 AMOT Zornitza Stark Classified gene: AMOT as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v0.132 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.131 AMOT Zornitza Stark reviewed gene: AMOT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.3440 AMOT Zornitza Stark Marked gene: AMOT as ready
Mendeliome v1.3440 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Mendeliome v1.3440 AMOT Zornitza Stark Classified gene: AMOT as Red List (low evidence)
Mendeliome v1.3440 AMOT Zornitza Stark Gene: amot has been classified as Red List (Low Evidence).
Mendeliome v1.3439 AMOT Zornitza Stark reviewed gene: AMOT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v1.379 EIF3B Zornitza Stark Marked gene: EIF3B as ready
Intellectual disability syndromic and non-syndromic v1.379 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.379 EIF3B Zornitza Stark Classified gene: EIF3B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.379 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.378 EIF3B Zornitza Stark gene: EIF3B was added
gene: EIF3B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3B were set to 41033306
Phenotypes for gene: EIF3B were set to Syndromic disease (MONDO:0002254), EIF3B-related
Review for gene: EIF3B was set to GREEN
Added comment: Fourteen individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Mendeliome v1.3439 EIF3B Zornitza Stark Marked gene: EIF3B as ready
Mendeliome v1.3439 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Mendeliome v1.3439 EIF3B Zornitza Stark Classified gene: EIF3B as Green List (high evidence)
Mendeliome v1.3439 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Mendeliome v1.3438 EIF3B Zornitza Stark gene: EIF3B was added
gene: EIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3B were set to 41033306
Phenotypes for gene: EIF3B were set to Syndromic disease (MONDO:0002254), EIF3B-related
Review for gene: EIF3B was set to GREEN
Added comment: Fourteen individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Congenital Heart Defect v0.474 EIF3B Zornitza Stark Marked gene: EIF3B as ready
Congenital Heart Defect v0.474 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.474 EIF3B Zornitza Stark Classified gene: EIF3B as Green List (high evidence)
Congenital Heart Defect v0.474 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.473 EIF3B Zornitza Stark gene: EIF3B was added
gene: EIF3B was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3B were set to 41033306
Phenotypes for gene: EIF3B were set to Syndromic disease (MONDO:0002254), EIF3B-related
Review for gene: EIF3B was set to GREEN
Added comment: Fourteen individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Fetal anomalies v1.456 EIF3B Zornitza Stark changed review comment from: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature; to: Fourteen individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Fetal anomalies v1.456 EIF3B Zornitza Stark Marked gene: EIF3B as ready
Fetal anomalies v1.456 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Fetal anomalies v1.456 EIF3B Zornitza Stark Classified gene: EIF3B as Green List (high evidence)
Fetal anomalies v1.456 EIF3B Zornitza Stark Gene: eif3b has been classified as Green List (High Evidence).
Fetal anomalies v1.455 EIF3B Zornitza Stark gene: EIF3B was added
gene: EIF3B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3B were set to 41033306
Phenotypes for gene: EIF3B were set to Syndromic disease (MONDO:0002254), EIF3B-related
Review for gene: EIF3B was set to GREEN
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Fetal anomalies v1.454 EIF3A Zornitza Stark Marked gene: EIF3A as ready
Fetal anomalies v1.454 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Fetal anomalies v1.454 EIF3A Zornitza Stark Classified gene: EIF3A as Green List (high evidence)
Fetal anomalies v1.454 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Fetal anomalies v1.453 EIF3A Zornitza Stark gene: EIF3A was added
gene: EIF3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EIF3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3A were set to 41033306
Phenotypes for gene: EIF3A were set to Syndromic disease (MONDO:0002254), EIF3A-related
Review for gene: EIF3A was set to GREEN
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Congenital Heart Defect v0.472 EIF3A Zornitza Stark Marked gene: EIF3A as ready
Congenital Heart Defect v0.472 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.472 EIF3A Zornitza Stark Classified gene: EIF3A as Green List (high evidence)
Congenital Heart Defect v0.472 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.471 EIF3A Zornitza Stark gene: EIF3A was added
gene: EIF3A was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: EIF3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3A were set to 41033306
Phenotypes for gene: EIF3A were set to Syndromic disease (MONDO:0002254), EIF3A-related
Review for gene: EIF3A was set to GREEN
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Mendeliome v1.3437 EIF3A Zornitza Stark Marked gene: EIF3A as ready
Mendeliome v1.3437 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Mendeliome v1.3437 EIF3A Zornitza Stark Classified gene: EIF3A as Green List (high evidence)
Mendeliome v1.3437 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Mendeliome v1.3436 EIF3A Zornitza Stark gene: EIF3A was added
gene: EIF3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3A were set to 41033306
Phenotypes for gene: EIF3A were set to Syndromic disease (MONDO:0002254), EIF3A-related
Review for gene: EIF3A was set to GREEN
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.377 EIF3A Zornitza Stark Marked gene: EIF3A as ready
Intellectual disability syndromic and non-syndromic v1.377 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.377 EIF3A Zornitza Stark Classified gene: EIF3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.377 EIF3A Zornitza Stark Gene: eif3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.376 EIF3A Zornitza Stark changed review comment from: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature; to: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.376 EIF3A Zornitza Stark edited their review of gene: EIF3A: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.376 EIF3A Zornitza Stark gene: EIF3A was added
gene: EIF3A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EIF3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF3A were set to 41033306
Phenotypes for gene: EIF3A were set to Syndromic disease (MONDO:0002254), EIF3A-related
Added comment: Four individuals reported with mono-allelic variants. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities. Zebrafish model recapitulated phenotype.
Sources: Literature
Mendeliome v1.3435 SF1 Zornitza Stark Marked gene: SF1 as ready
Mendeliome v1.3435 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Mendeliome v1.3435 SF1 Zornitza Stark Classified gene: SF1 as Green List (high evidence)
Mendeliome v1.3435 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.375 SF1 Zornitza Stark Marked gene: SF1 as ready
Intellectual disability syndromic and non-syndromic v1.375 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.375 SF1 Zornitza Stark Classified gene: SF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.375 SF1 Zornitza Stark Gene: sf1 has been classified as Green List (High Evidence).
Mendeliome v1.3434 MDGA2 Zornitza Stark Marked gene: MDGA2 as ready
Mendeliome v1.3434 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Mendeliome v1.3434 MDGA2 Zornitza Stark Classified gene: MDGA2 as Green List (high evidence)
Mendeliome v1.3434 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.374 MDGA2 Zornitza Stark Marked gene: MDGA2 as ready
Intellectual disability syndromic and non-syndromic v1.374 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.374 MDGA2 Zornitza Stark Classified gene: MDGA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.374 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.373 MDGA2 Zornitza Stark gene: MDGA2 was added
gene: MDGA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760
Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092
Review for gene: MDGA2 was set to GREEN
Added comment: Affected individuals present with a broad neurodevelopmental impairment-like phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Literature
Genetic Epilepsy v1.254 MDGA2 Zornitza Stark Marked gene: MDGA2 as ready
Genetic Epilepsy v1.254 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.254 MDGA2 Zornitza Stark Classified gene: MDGA2 as Green List (high evidence)
Genetic Epilepsy v1.254 MDGA2 Zornitza Stark Gene: mdga2 has been classified as Green List (High Evidence).
Fetal anomalies v1.452 WNT4 Zornitza Stark Publications for gene: WNT4 were set to 22503279; 21377155; 16959810; 18179883; 15317892; 18182450
Fetal anomalies v1.451 WNT4 Zornitza Stark edited their review of gene: WNT4: Added comment: Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses.

PMID 40992710 reports second affected family, consanguineous, which had an affected fetus with CDH and an affected child had orofacial clefting.
A subset of Wnt4 null mouse embryos had perimembranous VSDs, anterior and posterior sac CDH, and soft palate clefts.

Bi-allelic association: two consanguineous families and a mouse model, maintain AMBER rating.; Changed publications: 22503279, 21377155, 16959810, 18179883, 40992710
Mendeliome v1.3433 WNT4 Zornitza Stark Publications for gene: WNT4 were set to 22503279; 21377155; 16959810; 18179883; 15317892; 18182450
Mendeliome v1.3432 WNT4 Zornitza Stark edited their review of gene: WNT4: Changed publications: 22503279, 21377155, 16959810, 18179883, 15317892, 18182450, 40992710
Mendeliome v1.3432 WNT4 Zornitza Stark commented on gene: WNT4: Biallelic variants in WNT4 have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses.

PMID 40992710 reports second affected family, consanguineous, which had an affected fetus with CDH and an affected child had orofacial clefting.

A subset of Wnt4 null mouse embryos had perimembranous VSDs, anterior and posterior sac CDH, and soft palate clefts.

Bi-allelic association: two consanguineous families and a mouse model, maintain AMBER rating.
Fetal anomalies v1.451 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Fetal anomalies v1.450 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to 33495992
Fetal anomalies v1.449 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Fetal anomalies v1.449 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.152 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Monogenic Diabetes v0.151 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to PMID: 33495992
Monogenic Diabetes v0.150 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Monogenic Diabetes v0.150 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.43 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Renal Ciliopathies and Nephronophthisis v1.42 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to PMID: 33495992
Renal Ciliopathies and Nephronophthisis v1.41 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.41 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.18 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to PMID: 33495992
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.17 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.16 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.16 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Ciliopathies v1.91 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Ciliopathies v1.90 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to 33495992
Ciliopathies v1.89 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Ciliopathies v1.89 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Mendeliome v1.3432 PDIA6 Zornitza Stark Phenotypes for gene: PDIA6 were changed from Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes to multiple congenital anomalies, MONDO:0019042, PDIA6-related
Mendeliome v1.3431 PDIA6 Zornitza Stark Publications for gene: PDIA6 were set to
Mendeliome v1.3430 PDIA6 Zornitza Stark Classified gene: PDIA6 as Green List (high evidence)
Mendeliome v1.3430 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.149 MIA3 Zornitza Stark Marked gene: MIA3 as ready
Monogenic Diabetes v0.149 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.149 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Monogenic Diabetes v0.149 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.148 MIA3 Zornitza Stark gene: MIA3 was added
gene: MIA3 was added to Monogenic Diabetes. Sources: Literature
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to 32101163; 33778321; 40948380; 40119123
Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269
Review for gene: MIA3 was set to GREEN
Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Three unrelated families reported, including four affected siblings. Mouse model has absence of bone mineralization.
Sources: Literature
Deafness_IsolatedAndComplex v1.236 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.236 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.235 MIA3 Zornitza Stark Marked gene: MIA3 as ready
Deafness_IsolatedAndComplex v1.235 MIA3 Zornitza Stark Gene: mia3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.235 MIA3 Zornitza Stark gene: MIA3 was added
gene: MIA3 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to 32101163; 33778321; 40948380; 40119123
Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269
Review for gene: MIA3 was set to GREEN
Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Three unrelated families reported, including four affected siblings. Mouse model has absence of bone mineralization.
Sources: Literature
Fetal anomalies v1.448 MIA3 Zornitza Stark Publications for gene: MIA3 were set to PMID: 32101163; 33778321
Fetal anomalies v1.447 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Fetal anomalies v1.447 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Fetal anomalies v1.446 MIA3 Zornitza Stark reviewed gene: MIA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40948380, 40119123; Phenotypes: Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.341 MIA3 Zornitza Stark Publications for gene: MIA3 were set to 32101163; 33778321; 40948380; 40119123
Skeletal dysplasia v0.341 MIA3 Zornitza Stark Publications for gene: MIA3 were set to 32101163; 33778321
Skeletal dysplasia v0.340 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Skeletal dysplasia v0.340 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.339 MIA3 Zornitza Stark edited their review of gene: MIA3: Changed rating: GREEN
Skeletal dysplasia v0.339 MIA3 Zornitza Stark edited their review of gene: MIA3: Added comment: Upgrade to Green Two additional unrelated individuals from consanguineous families with biallelic variants. Affected individuals presented with short stature, metaphyseal dysplasia, dentinogenesis imperfecta, dental anomalies, and hearing loss.; Changed publications: 32101163, 33778321, 40948380, 40119123
Mendeliome v1.3429 MIA3 Zornitza Stark Publications for gene: MIA3 were set to 32101163; 33778321
Mendeliome v1.3428 MIA3 Zornitza Stark Classified gene: MIA3 as Green List (high evidence)
Mendeliome v1.3428 MIA3 Zornitza Stark Gene: mia3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.40 CASP8 Zornitza Stark Marked gene: CASP8 as ready
Hereditary Neuropathy - complex v1.40 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.40 CASP8 Zornitza Stark Classified gene: CASP8 as Green List (high evidence)
Hereditary Neuropathy - complex v1.40 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.39 CASP8 Zornitza Stark gene: CASP8 was added
gene: CASP8 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: CASP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP8 were set to 41026346
Phenotypes for gene: CASP8 were set to Autoimmune lymphoproliferative syndrome, type IIB MIM#607271
Review for gene: CASP8 was set to GREEN
Added comment: 7 individuals from 5 families reported with ALPS. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation.

GREEN but any variants apart from the founder variant should be treated with caution.
Sources: Literature
Autoimmune Lymphoproliferative Syndrome v1.11 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
Autoimmune Lymphoproliferative Syndrome v1.11 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v1.11 IKZF1 Zornitza Stark Classified gene: IKZF1 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v1.11 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v1.10 CASP8 Zornitza Stark Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Autoimmune Lymphoproliferative Syndrome v1.9 CASP8 Zornitza Stark Classified gene: CASP8 as Green List (high evidence)
Autoimmune Lymphoproliferative Syndrome v1.9 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Autoimmune Lymphoproliferative Syndrome v1.8 CASP8 Zornitza Stark changed review comment from: Additional individual reported, bring up total to 7 individuals from 5 families. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation. GREEN but any variants apart from the founder variant should be treated with caution.; to: Additional individual reported, bring up total to 7 individuals from 5 families. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation.

GREEN but any variants apart from the founder variant should be treated with caution.
Autoimmune Lymphoproliferative Syndrome v1.8 CASP8 Zornitza Stark reviewed gene: CASP8: Rating: GREEN; Mode of pathogenicity: None; Publications: 41026346; Phenotypes: Autoimmune lymphoproliferative syndrome, type IIB MIM#607271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v1.33 CASP8 Zornitza Stark Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Disorders of immune dysregulation v1.32 CASP8 Zornitza Stark Classified gene: CASP8 as Green List (high evidence)
Disorders of immune dysregulation v1.32 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v1.31 CASP8 Zornitza Stark Tag founder tag was added to gene: CASP8.
Disorders of immune dysregulation v1.31 CASP8 Zornitza Stark edited their review of gene: CASP8: Added comment: Additional individual reported, bring up total to 7 individuals from 5 families. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation.

GREEN but any variants apart from the founder variant should be treated with caution.; Changed rating: GREEN; Changed publications: 12353035, 25814141, 12654726, 17213198, 16148088, 41026346
Mendeliome v1.3427 CASP8 Zornitza Stark Publications for gene: CASP8 were set to 12353035; 25814141; 12654726; 17213198; 16148088
Mendeliome v1.3426 CASP8 Zornitza Stark Classified gene: CASP8 as Green List (high evidence)
Mendeliome v1.3426 CASP8 Zornitza Stark Gene: casp8 has been classified as Green List (High Evidence).
Mendeliome v1.3425 CASP8 Zornitza Stark Tag founder tag was added to gene: CASP8.
Mendeliome v1.3425 CASP8 Zornitza Stark edited their review of gene: CASP8: Added comment: Additional individual reported, bring up total to 7 individuals from 5 families. All had the same homozygous missense variant, p.Arg265Trp. Some known to be distantly related. CIDP was a common manifestation.

GREEN but any variants apart from the founder variant should be treated with caution.; Changed rating: GREEN; Changed publications: 41026346; Changed phenotypes: Autoimmune lymphoproliferative syndrome, type IIB MIM#607271; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3425 PTBP1 Zornitza Stark Phenotypes for gene: PTBP1 were changed from to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related
Mendeliome v1.3424 PTBP1 Zornitza Stark Publications for gene: PTBP1 were set to
Mendeliome v1.3423 PTBP1 Zornitza Stark Mode of inheritance for gene: PTBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3422 PTBP1 Zornitza Stark Classified gene: PTBP1 as Green List (high evidence)
Mendeliome v1.3422 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.446 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Fetal anomalies v1.446 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.446 PTBP1 Zornitza Stark Classified gene: PTBP1 as Green List (high evidence)
Fetal anomalies v1.446 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.339 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Skeletal dysplasia v0.339 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.339 PTBP1 Zornitza Stark Classified gene: PTBP1 as Green List (high evidence)
Skeletal dysplasia v0.339 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.372 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Intellectual disability syndromic and non-syndromic v1.372 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.372 PTBP1 Zornitza Stark Classified gene: PTBP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.372 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.108 CACNB1 Zornitza Stark Marked gene: CACNB1 as ready
Muscular dystrophy and myopathy_Paediatric v1.108 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.108 CACNB1 Zornitza Stark Classified gene: CACNB1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.108 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.107 CACNB1 Zornitza Stark gene: CACNB1 was added
gene: CACNB1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CACNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNB1 were set to 41023410
Phenotypes for gene: CACNB1 were set to Congenital muscular dystrophy MONDO:0020121, CACNB1-related
Review for gene: CACNB1 was set to AMBER
Added comment: PMID: 41023410 - Different phenotype - congenital muscular dystrophy. Only two consanguineous families have been reported with variants in this gene.

3 individuals from two unrelated consanguineous families present with myopathy, elevated CK levels and low body weight
Two biallelic rare variants were identified in CACNB1 - c.124_133del; p.(Asp42Argfs*37 and c.85-1G>A)
RNA assay was conducted on isolated RNA showed the generation of a PTC leading to a truncated protein.
Sources: Literature
Mendeliome v1.3421 CACNB1 Zornitza Stark Phenotypes for gene: CACNB1 were changed from Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related to Congenital muscular dystrophy MONDO:0020121; Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related
Mendeliome v1.3420 CACNB1 Zornitza Stark Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Mendeliome v1.3419 CACNB1 Zornitza Stark Mode of inheritance for gene: CACNB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3418 CACNB1 Zornitza Stark Classified gene: CACNB1 as Amber List (moderate evidence)
Mendeliome v1.3418 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.470 ZDHHC18 Zornitza Stark Marked gene: ZDHHC18 as ready
Congenital Heart Defect v0.470 ZDHHC18 Zornitza Stark Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3417 ZDHHC18 Zornitza Stark Marked gene: ZDHHC18 as ready
Mendeliome v1.3417 ZDHHC18 Zornitza Stark Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3417 SWSAP1 Zornitza Stark Marked gene: SWSAP1 as ready
Mendeliome v1.3417 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Mendeliome v1.3417 SWSAP1 Zornitza Stark Classified gene: SWSAP1 as Red List (low evidence)
Mendeliome v1.3417 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.362 SWSAP1 Zornitza Stark Marked gene: SWSAP1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.362 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.362 SWSAP1 Zornitza Stark Classified gene: SWSAP1 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.362 SWSAP1 Zornitza Stark Gene: swsap1 has been classified as Red List (Low Evidence).
Hereditary Neuropathy_CMT - isolated v1.67 NAMPT Zornitza Stark Marked gene: NAMPT as ready
Hereditary Neuropathy_CMT - isolated v1.67 NAMPT Zornitza Stark Gene: nampt has been classified as Red List (Low Evidence).
Hereditary Neuropathy_CMT - isolated v1.67 NAMPT Zornitza Stark gene: NAMPT was added
gene: NAMPT was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: NAMPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAMPT were set to 41004591
Phenotypes for gene: NAMPT were set to hereditary motor and sensory neuropathy MONDO:0015358
Review for gene: NAMPT was set to RED
Added comment: Two individuals from a single family reported with sensory and motor neuropathy with motor coordination impairment, muscle atrophy/weakness, foot/hand deformities, loss of sensation and positive Babinski sign

Homozygous missense, c.472G>C (p.P158A), absent from gnomAD.

Functional Studies: recombinant NAMPT protein activity assay; thermal shift stability assay; patient fibroblast bioenergetic, mitochondrial and oxidative stress assays; CRISPR‑generated isogenic fibroblasts; homozygous p.P158A mouse model showing metabolic, synaptic and motor neuron defects; rescue with NMN/P7C3
Sources: Literature
Fetal anomalies v1.445 FAP Zornitza Stark Marked gene: FAP as ready
Fetal anomalies v1.445 FAP Zornitza Stark Gene: fap has been classified as Red List (Low Evidence).
Fetal anomalies v1.445 FAP Zornitza Stark gene: FAP was added
gene: FAP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAP were set to 40949908
Phenotypes for gene: FAP were set to congenital pulmonary airway malformation MONDO:0016580
Review for gene: FAP was set to RED
Added comment: Only 1 reported fetus with a diagnosis of congenital pulmonary airway malformation Heterozygous variant identified - c.T269G:p.L90W. The variant is present in gnomAD v4.1 - EAS AF - 0.007% (4 hets)
Sources: Literature
Mendeliome v1.3416 FAP Zornitza Stark Marked gene: FAP as ready
Mendeliome v1.3416 FAP Zornitza Stark Gene: fap has been classified as Red List (Low Evidence).
Mendeliome v1.3416 FAP Zornitza Stark Classified gene: FAP as Red List (low evidence)
Mendeliome v1.3416 FAP Zornitza Stark Gene: fap has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.371 DBX1 Zornitza Stark Marked gene: DBX1 as ready
Intellectual disability syndromic and non-syndromic v1.371 DBX1 Zornitza Stark Gene: dbx1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.371 DBX1 Zornitza Stark gene: DBX1 was added
gene: DBX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBX1 were set to 40995053
Phenotypes for gene: DBX1 were set to central hypoventilation syndrome, congenital MONDO:0800031
Review for gene: DBX1 was set to RED
Added comment: Single individual reported with congenital central hypoventilation syndrome (atypical CCHS) with central hypotonia, global developmental delay, seizures, autoaggressive behaviour. Consanguineous parents, hmz frameshift variant c.340_341delGC, absent from gnomAD.
Mouse Dbx1 knockout is lethal indicating essential role in respiration.
Sources: Literature
Central Hypoventilation v1.6 DBX1 Zornitza Stark Marked gene: DBX1 as ready
Central Hypoventilation v1.6 DBX1 Zornitza Stark Gene: dbx1 has been classified as Red List (Low Evidence).
Central Hypoventilation v1.6 DBX1 Zornitza Stark gene: DBX1 was added
gene: DBX1 was added to Central Hypoventilation. Sources: Literature
Mode of inheritance for gene: DBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBX1 were set to 40995053
Phenotypes for gene: DBX1 were set to central hypoventilation syndrome, congenital MONDO:0800031
Review for gene: DBX1 was set to RED
Added comment: Single individual reported with congenital central hypoventilation syndrome (atypical CCHS) with central hypotonia, global developmental delay, seizures, autoaggressive behaviour. Consanguineous parents, hmz frameshift variant c.340_341delGC, absent from gnomAD.
Mouse Dbx1 knockout is lethal indicating essential role in respiration.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.370 NFXL1 Zornitza Stark Marked gene: NFXL1 as ready
Intellectual disability syndromic and non-syndromic v1.370 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.370 NFXL1 Zornitza Stark Classified gene: NFXL1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.370 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.369 NFXL1 Zornitza Stark gene: NFXL1 was added
gene: NFXL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NFXL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFXL1 were set to 40430072; 41024252
Phenotypes for gene: NFXL1 were set to Syndromic disease (MONDO:0002254), NFXL1-related
Review for gene: NFXL1 was set to AMBER
Added comment: PMID: 40430072 2 siblings with psychosis and schizophrenia, homozygous for Cys441Tyr. Some modelling suggested a deleterious affect but no functional studies performed.

PMID: 41024252 8 patients from 7 families with joint hyperlaxity, with or without short stature and renal disease. 6 families were homozygous for p.(Cys539Trpfs*64) while the other two were homozygous for p.(Lys681*). Paper described both as founder variants but they are rare/absent in gnomad.

Joint hyperlaxity (7), chronic kidney disease/FSGS (2) small echogenic kidneys (3), acute kidney injury (1), dysmorphic features (6), short stature (6), speech delay (3).

One patient also had epilepsy, developmental delay and spasticity however c.728+1G>A in WDR45 explained this part of her phenotype. Other patients also had more severe outlying symptoms with no other explanation mentioned: 1 with developmental delay, hearing loss, brain malformations, skeletal abnormalities, and another a 3 year old who passed away following a complex medical course including blue sclera, proximal tibial fracture, severe respiratory distress due to a chest infection, and acute kidney injury.

Amber given the variable phenotype findings of the reported patients and only 2 homozygous variants identified so far.

Extent of associated DD/ID currently unclear but adding on this panel as it is often ordered in children with multi-system features suggestive of an underlying syndrome.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.159 NFXL1 Zornitza Stark Marked gene: NFXL1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.159 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.159 NFXL1 Zornitza Stark Classified gene: NFXL1 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.159 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.158 NFXL1 Zornitza Stark gene: NFXL1 was added
gene: NFXL1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: NFXL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFXL1 were set to 40430072; 41024252
Phenotypes for gene: NFXL1 were set to Syndromic disease (MONDO:0002254), NFXL1-related
Review for gene: NFXL1 was set to AMBER
Added comment: PMID: 40430072 2 siblings with psychosis and schizophrenia, homozygous for Cys441Tyr. Some modelling suggested a deleterious affect but no functional studies performed.

PMID: 41024252 8 patients from 7 families with joint hyperlaxity, with or without short stature and renal disease. 6 families were homozygous for p.(Cys539Trpfs*64) while the other two were homozygous for p.(Lys681*). Paper described both as founder variants but they are rare/absent in gnomad.

Joint hyperlaxity (7), chronic kidney disease/FSGS (2) small echogenic kidneys (3), acute kidney injury (1), dysmorphic features (6), short stature (6), speech delay (3).

One patient also had epilepsy, developmental delay and spasticity however c.728+1G>A in WDR45 explained this part of her phenotype. Other patients also had more severe outlying symptoms with no other explanation mentioned: 1 with developmental delay, hearing loss, brain malformations, skeletal abnormalities, and another a 3 year old who passed away following a complex medical course including blue sclera, proximal tibial fracture, severe respiratory distress due to a chest infection, and acute kidney injury.

Amber given the variable phenotype findings of the reported patients and only 2 homozygous variants identified so far. Kidney phenotype not entirely clear but likely to be within syndromic CAKUT spectrum.
Sources: Literature
Mendeliome v1.3415 NFXL1 Zornitza Stark Marked gene: NFXL1 as ready
Mendeliome v1.3415 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3415 NFXL1 Zornitza Stark Classified gene: NFXL1 as Amber List (moderate evidence)
Mendeliome v1.3415 NFXL1 Zornitza Stark Gene: nfxl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Marked gene: ZSWIM7 as ready
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Classified gene: ZSWIM7 as Green List (high evidence)
Mendeliome v1.3414 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.45 ZSWIM7 Zornitza Stark Marked gene: ZSWIM7 as ready
Infertility and Recurrent Pregnancy Loss v1.45 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.45 ZSWIM7 Zornitza Stark Classified gene: ZSWIM7 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.45 ZSWIM7 Zornitza Stark Gene: zswim7 has been classified as Green List (High Evidence).
Mendeliome v1.3413 PTBP2 Zornitza Stark Marked gene: PTBP2 as ready
Mendeliome v1.3413 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3413 PTBP2 Zornitza Stark Classified gene: PTBP2 as Amber List (moderate evidence)
Mendeliome v1.3413 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.368 PTBP2 Zornitza Stark Marked gene: PTBP2 as ready
Intellectual disability syndromic and non-syndromic v1.368 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.368 PTBP2 Zornitza Stark Classified gene: PTBP2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.368 PTBP2 Zornitza Stark Gene: ptbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3412 KLK15 Zornitza Stark Marked gene: KLK15 as ready
Mendeliome v1.3412 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Mendeliome v1.3412 KLK15 Zornitza Stark Classified gene: KLK15 as Red List (low evidence)
Mendeliome v1.3412 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Mendeliome v1.3411 KLK15 Zornitza Stark reviewed gene: KLK15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v1.100 KLK15 Zornitza Stark Marked gene: KLK15 as ready
Aortopathy_Connective Tissue Disorders v1.100 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.100 KLK15 Zornitza Stark Classified gene: KLK15 as Red List (low evidence)
Aortopathy_Connective Tissue Disorders v1.100 KLK15 Zornitza Stark Gene: klk15 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.99 KLK15 Zornitza Stark reviewed gene: KLK15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3411 INCENP Zornitza Stark Marked gene: INCENP as ready
Mendeliome v1.3411 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3411 INCENP Zornitza Stark Classified gene: INCENP as Amber List (moderate evidence)
Mendeliome v1.3411 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.44 INCENP Zornitza Stark Marked gene: INCENP as ready
Infertility and Recurrent Pregnancy Loss v1.44 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.44 INCENP Zornitza Stark Classified gene: INCENP as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.44 INCENP Zornitza Stark Gene: incenp has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3410 GSTZ1 Zornitza Stark Marked gene: GSTZ1 as ready
Mendeliome v1.3410 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Green List (High Evidence).
Mendeliome v1.3410 GSTZ1 Zornitza Stark Classified gene: GSTZ1 as Green List (high evidence)
Mendeliome v1.3410 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.137 GSTZ1 Zornitza Stark Publications for gene: GSTZ1 were set to 27876694
Aminoacidopathy v1.136 GSTZ1 Zornitza Stark Classified gene: GSTZ1 as Green List (high evidence)
Aminoacidopathy v1.136 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Green List (High Evidence).
Mendeliome v1.3409 FSIP2 Zornitza Stark Marked gene: FSIP2 as ready
Mendeliome v1.3409 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Mendeliome v1.3409 FSIP2 Zornitza Stark Classified gene: FSIP2 as Green List (high evidence)
Mendeliome v1.3409 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.43 FSIP2 Zornitza Stark Marked gene: FSIP2 as ready
Infertility and Recurrent Pregnancy Loss v1.43 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v1.43 FSIP2 Zornitza Stark Classified gene: FSIP2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v1.43 FSIP2 Zornitza Stark Gene: fsip2 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.234 CDK9 Zornitza Stark Marked gene: CDK9 as ready
Syndromic Retinopathy v0.234 CDK9 Zornitza Stark Gene: cdk9 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.234 CDK9 Zornitza Stark Classified gene: CDK9 as Green List (high evidence)
Syndromic Retinopathy v0.234 CDK9 Zornitza Stark Gene: cdk9 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.233 CDK9 Zornitza Stark gene: CDK9 was added
gene: CDK9 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK9 were set to 40954203; 33640901; 30237576; 26633546
Phenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy
Review for gene: CDK9 was set to GREEN
Added comment: Biallelic variants in at least six families, though 4 may be related:
1) proband that displays retinal dystrophy without a CHARGE-like malformation syndrome (c.862G>A/p.A288T + c.961C>T/p.P321S).
2) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C),
3-7) 4 consanguineous families homozygous for p.R225C, including a set of cousins.
CDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy
Sources: Literature
Fetal anomalies v1.444 CDK9 Zornitza Stark Marked gene: CDK9 as ready
Fetal anomalies v1.444 CDK9 Zornitza Stark Gene: cdk9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.444 CDK9 Zornitza Stark Classified gene: CDK9 as Amber List (moderate evidence)
Fetal anomalies v1.444 CDK9 Zornitza Stark Gene: cdk9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.443 CDK9 Zornitza Stark gene: CDK9 was added
gene: CDK9 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK9 were set to 33640901; 30237576; 26633546
Phenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy
Review for gene: CDK9 was set to AMBER
Added comment: Two independent reports of relevance to this panel:
1) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C),
2) 4 consanguineous families homozygous for p.R225C, including a set of cousins. CDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy.

One additional family with retinal dystrophy only.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.367 CDK9 Zornitza Stark Marked gene: CDK9 as ready
Intellectual disability syndromic and non-syndromic v1.367 CDK9 Zornitza Stark Gene: cdk9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.367 CDK9 Zornitza Stark Classified gene: CDK9 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.367 CDK9 Zornitza Stark Gene: cdk9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.366 CDK9 Zornitza Stark gene: CDK9 was added
gene: CDK9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK9 were set to 33640901; 30237576; 26633546
Phenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy
Review for gene: CDK9 was set to AMBER
Added comment: Two independent reports:
1) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C),
2) 4 consanguineous families homozygous for p.R225C, including a set of cousins.
CDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy

One additional family with retinal dystrophy only.
Sources: Literature
Mendeliome v1.3408 CDK9 Zornitza Stark Marked gene: CDK9 as ready
Mendeliome v1.3408 CDK9 Zornitza Stark Gene: cdk9 has been classified as Green List (High Evidence).
Mendeliome v1.3407 ABCB4 Chirag Patel Publications for gene ABCB4 were changed from 8666348; 17726488; 18482588; 28924228; 32376413; 9419367; 26474921; 32793533; 11313315 to 8666348; 17726488; 18482588; 28924228; 32376413; 9419367; 26474921; 32793533; 11313315
Mendeliome v1.3406 ABCB4 Chirag Patel Source Victorian Clinical Genetics Services was removed from ABCB4.
Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803) to Progressive familial intrahepatic cholestasis type 3, MONDO:0011214; Cholestasis, intrahepatic, of pregnancy, 3 MIM#614972; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803)
Miscellaneous Metabolic Disorders v1.56 ABCB4 Chirag Patel Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism to Progressive familial intrahepatic cholestasis type 3, MONDO:0011214
Publications for gene ABCB4 were changed from 8666348, 9419367, 26474921, 32793533, 11313315 to 8666348, 9419367, 26474921, 32793533, 11313315
Liver Failure_Paediatric v1.28 ABCB4 Chirag Patel Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3, MIM# 602347 to Progressive familial intrahepatic cholestasis type 3, MONDO:0011214
Publications for gene ABCB4 were changed from 17726488, 9419367, 26474921, 32793533, 11313315 to 17726488, 9419367, 26474921, 32793533, 11313315
Mendeliome v1.3405 ABCC8 Chirag Patel Source Victorian Clinical Genetics Services was removed from ABCC8.
Source Expert list was added to ABCC8.
Phenotypes for gene: ABCC8 were changed from Maturity-onset diabetes of the young, type 12, MIM# 621196; Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800 to Maturity-onset diabetes of the young, type 12, MIM# 621196; Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800; Pulmonary arterial hypertension, MONDO:0015924, ABCC8-related
Publications for gene ABCC8 were changed from 21054355, 32027066, 32376986, 30354297, 35811711, 32934261, 31727138 to 21054355, 32027066, 32376986, 30354297, 35811711, 32934261, 31727138
Pulmonary Arterial Hypertension v1.44 ABCC8 Chirag Patel Phenotypes for gene: ABCC8 were changed from Diabetes mellitus; Hypoglycaemia; Pulmonary arterial hypertension to Pulmonary arterial hypertension, MONDO:0015924, ABCC8-related
Publications for gene ABCC8 were changed from 30354297, 35811711, 32934261, 31727138 to 30354297, 35811711, 32934261, 31727138
Intellectual disability syndromic and non-syndromic v1.365 AGTPBP1 Chirag Patel 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, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Hereditary Neuropathy - complex v1.38 AGTPBP1 Chirag Patel 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, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Regression v0.588 AGTPBP1 Chirag Patel 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, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Ataxia v1.58 AGTPBP1 Chirag Patel 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, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Mendeliome v1.3404 AGTPBP1 Chirag Patel 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, MONDO:0032650
Publications for gene AGTPBP1 were changed from 30420557, 28600779, 30976113, 38153683, 28325758 to 30420557, 28600779, 30976113, 38153683, 28325758
Polymicrogyria and Schizencephaly v0.201 ATP1A3 Chirag Patel Source Literature was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Polymicrogyria; epilepsy; developmental delay to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 33762331, 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 33762331, 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Alternating Hemiplegia and Hemiplegic Migraine v0.61 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM# 614820 to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 22850527, 24842602,15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 22850527, 24842602,15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Brain Channelopathies v1.5 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235 to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Cerebral Palsy v1.397 ATP1A3 Chirag Patel Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235 to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Genetic Epilepsy v1.253 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Source Australian Genomics Health Alliance Epilepsy Flagship was removed from ATP1A3.
Phenotypes for gene: ATP1A3 were changed from developmental and epileptic encephalopathy; early or neonatal onset seizures, polymicrogyria to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Mendeliome v1.3403 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235; Polymicrogyria to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Regression v0.587 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Mode of inheritance for gene ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP1A3 were changed from to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Intellectual disability syndromic and non-syndromic v1.364 ATP1A3 Chirag Patel Source Genetic Health Queensland was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM#614820; Developmental and epileptic encephalopathy, polymicrogyria to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 33880529, 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Paroxysmal Dyskinesia v0.144 ATP1A3 Chirag Patel Source Royal Children's Hospital Neurology Department was removed from ATP1A3.
Source Victorian Clinical Genetics Services was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Mode of inheritance for gene ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP1A3 were changed from to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Ataxia v1.57 ATP1A3 Chirag Patel Source Victorian Clinical Genetics Services was removed from ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2 MIM#614820; CAPOS syndrome MIM#601338 to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Dystonia - isolated/combined v1.42 ATP1A3 Chirag Patel Source Royal Melbourne Hospital was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Dystonia-12, MIM# 128235; Rapid dystonia-parkinsonism MONDO:0007496 to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953; 17282997; 19351654, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953; 17282997; 19351654, 22842232, 24468074, 33762331, 29861155, 31425744
Fetal anomalies v1.442 ATP1A3 Chirag Patel Source Genomics England PanelApp was removed from ATP1A3.
Source Literature was removed from ATP1A3.
Source Genetic Health Queensland was removed from ATP1A3.
Source Expert list was added to ATP1A3.
Phenotypes for gene: ATP1A3 were changed from Developmental and epileptic encephalopathy 99, MIM# 619606; Polymicrogyria to ATP1A3-associated neurological disorder, MONDO:0700002
Publications for gene ATP1A3 were changed from 15260953, 22842232, 24468074, 33762331, 29861155, 31425744 to 15260953, 22842232, 24468074, 33762331, 29861155, 31425744
Intellectual disability syndromic and non-syndromic v1.363 ALS2 Chirag Patel Source Genetic Health Queensland was removed from ALS2.
Source ClinGen was added to ALS2.
Phenotypes for gene: ALS2 were changed from Spastic paralysis, infantile onset ascending, MIM#607225 to ALS2-related motor neuron disease, MONDO:0100227
Motor Neurone Disease v1.39 ALS2 Chirag Patel Source Literature was removed from ALS2.
Source Melbourne Genomics Health Alliance Complex Neurology Flagship was removed from ALS2.
Source Victorian Clinical Genetics Services was removed from ALS2.
Source ClinGen was added to ALS2.
Phenotypes for gene: ALS2 were changed from Amyotrophic lateral sclerosis 2, juvenile (MIM# 205100; MONDO: MONDO:0008780) to ALS2-related motor neuron disease, MONDO:0100227
Publications for gene ALS2 were changed from 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358 to 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358
Cerebral Palsy v1.396 ALS2 Chirag Patel Phenotypes for gene: ALS2 were changed from Spastic paralysis, infantile onset ascending, MIM# 607225 to ALS2-related motor neuron disease, MONDO:0100227
Publications for gene ALS2 were changed from 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358 to 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358
Hereditary Spastic Paraplegia v1.101 ALS2 Chirag Patel Source Royal Melbourne Hospital was removed from ALS2.
Source ClinGen was added to ALS2.
Phenotypes for gene: ALS2 were changed from Spastic paralysis, infantile onset ascending, MIM# 607225 to ALS2-related motor neuron disease, MONDO:0100227
Publications for gene ALS2 were changed from 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358 to 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358
Mendeliome v1.3402 ALS2 Chirag Patel Source Literature was removed from ALS2.
Source ClinGen was added to ALS2.
Phenotypes for gene: ALS2 were changed from Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353) to ALS2-related motor neuron disease, MONDO:0100227
Publications for gene ALS2 were changed from 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358 to 30128655, 33409823, 11586298, 16240357, 23282280, 24562058, 33155358
Muscular dystrophy and myopathy_Paediatric v1.106 ALG14 Chirag Patel reviewed gene: ALG14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v1.106 ALG14 Chirag Patel Classified gene: ALG14 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.106 ALG14 Chirag Patel Gene: alg14 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.105 ALG14 Chirag Patel Phenotypes for gene: ALG14 were changed from congenital myopathy MONDO:0019952 to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Intellectual disability syndromic and non-syndromic v1.362 ALG14 Chirag Patel Source Genetic Health Queensland was removed from ALG14.
Source Expert list was added to ALG14.
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Congenital Myasthenia v1.16 ALG14 Chirag Patel Classified gene: ALG14 as Green List (high evidence)
Congenital Myasthenia v1.16 ALG14 Chirag Patel Gene: alg14 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.252 ALG14 Chirag Patel Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Regression v0.586 ALG14 Chirag Patel Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Congenital Myasthenia v1.15 ALG14 Chirag Patel Source Royal Melbourne Hospital was removed from ALG14.
Source Expert list was added to ALG14.
Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Congenital Disorders of Glycosylation v1.78 ALG14 Chirag Patel Source Victorian Clinical Genetics Services was removed from ALG14.
Source Expert list was added to ALG14.
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Mendeliome v1.3401 ALG14 Chirag Patel Source Victorian Clinical Genetics Services was removed from ALG14.
Source Expert list was added to ALG14.
Publications for gene ALG14 were changed from 30221345, 23404334, 28733338, 33751823, 34971077 to 30221345, 23404334, 28733338, 33751823, 34971077
Mitochondrial disease v0.1085 AGK Chirag Patel Source Victorian Clinical Genetics Services was removed from AGK.
Source Australian Genomics Health Alliance Mitochondrial Flagship was removed from AGK.
Source Expert list was added to AGK.
Mode of inheritance for gene AGK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGK were changed from to Sengers syndrome, MIM#212350
Publications for gene AGK were changed from 22415731; 25208612; 22415731; 25208612 to 22415731; 25208612; 22415731; 25208612
Mendeliome v1.3400 AGK Chirag Patel Source Victorian Clinical Genetics Services was removed from AGK.
Source Expert list was added to AGK.
Deafness_IsolatedAndComplex v1.234 ATP6V1B2 Chirag Patel Source Literature was removed from ATP6V1B2.
Source Expert list was added to ATP6V1B2.
Mode of inheritance for gene ATP6V1B2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3399 DHX9 Chirag Patel Source Literature was removed from DHX9.
Source Expert list was added to DHX9.
Phenotypes for gene: DHX9 were changed from Intellectual developmental disorder, autosomal dominant 75, MIM# 620988; Charcot-Marie-Tooth disease, MONDO:0015626 to Intellectual developmental disorder, autosomal dominant 75, MIM# 620988; Charcot-Marie-Tooth disease, MONDO:0015626, DHX9-related
Liver Failure_Paediatric v1.27 DGUOK Chirag Patel Phenotypes for gene: DGUOK were changed from Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM#251880 to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Mitochondrial disease v0.1084 DGUOK Chirag Patel Source Victorian Clinical Genetics Services was removed from DGUOK.
Source Australian Genomics Health Alliance Mitochondrial Flagship was removed from DGUOK.
Source Victorian Clinical Genetics Services was removed from DGUOK.
Source ClinGen was added to DGUOK.
Mode of inheritance for gene DGUOK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DGUOK were changed from to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Cholestasis v1.5 DGUOK Chirag Patel Source Victorian Clinical Genetics Services was removed from DGUOK.
Source ClinGen was added to DGUOK.
Phenotypes for gene: DGUOK were changed from Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880 to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Hereditary Neuropathy - complex v1.37 DGUOK Chirag Patel Phenotypes for gene: DGUOK were changed from Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880 Portal hypertension, noncirrhotic, 617068 Neonatal liver failure, myopathy, sensory-motor axonal neuropathy to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Mendeliome v1.3398 DGUOK Chirag Patel Source Victorian Clinical Genetics Services was removed from DGUOK.
Source ClinGen was added to DGUOK.
Publications for gene DGUOK were changed from 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938 to 11687800, 12874104, 15887277, 23043144, 26874653, 18205204, 29137425, 30956829, 35750291, 28215579, 20301766, 28215579, 17073823, 31127938
Mendeliome v1.3397 DHH Chirag Patel Classified gene: DHH as Green List (high evidence)
Mendeliome v1.3397 DHH Chirag Patel Gene: dhh has been classified as Green List (High Evidence).
Differences of Sex Development v1.24 DHH Chirag Patel Source Victorian Clinical Genetics Services was removed from DHH.
Source Expert list was added to DHH.
Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 to 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Mendeliome v1.3396 DHH Chirag Patel Source Victorian Clinical Genetics Services was removed from DHH.
Source Expert list was added to DHH.
Phenotypes for gene: DHH were changed from 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; 46XY sex reversal 7 MIM#233420 to 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hereditary Neuropathy - complex v1.36 DHH Chirag Patel Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 to 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Infertility and Recurrent Pregnancy Loss v1.42 DHH Chirag Patel Phenotypes for gene: DHH were changed from MONDO:0011766 to 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Infertility and Recurrent Pregnancy Loss v1.41 DHH Chirag Patel Source Literature was removed from DHH.
Source Expert list was added to DHH.
Phenotypes for gene: DHH were changed from 46XY gonadal dysgenesis with minifascicular neuropathy, MIM# 607080 to MONDO:0011766
Genetic Epilepsy v1.251 DNAJC6 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAJC6.
Source Australian Genomics Health Alliance Epilepsy Flagship was removed from DNAJC6.
Source Expert list was added to DNAJC6.
Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19b, early-onset, MIM#615528 to Parkinson disease 19a, juvenile-onset - MIM#615528; Parkinson disease 19b, early-onset - MIM#615528
Publications for gene DNAJC6 were changed from 22563501, 23211418, 26528954, 33983693 to 22563501, 23211418, 26528954, 33983693
Early-onset Parkinson disease v2.43 DNAJC6 Chirag Patel Publications for gene DNAJC6 were changed from 22563501, 23211418, 26528954, 33983693 to 22563501, 23211418, 26528954, 33983693
Mendeliome v1.3394 DNAJC6 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAJC6.
Source Expert list was added to DNAJC6.
Publications for gene DNAJC6 were changed from 22563501, 23211418, 26528954, 33983693 to 22563501, 23211418, 26528954, 33983693
Early-onset Parkinson disease v2.42 DNAJC6 Chirag Patel Source Melbourne Genomics Health Alliance Complex Neurology Flagship was removed from DNAJC6.
Source Victorian Clinical Genetics Services was removed from DNAJC6.
Source Expert list was added to DNAJC6.
Phenotypes for gene: DNAJC6 were changed from juvenile onset Parkinson disease 19A MONDO:0014231 to Parkinson disease 19a, juvenile-onset - MIM#615528; Parkinson disease 19b, early-onset - MIM#615528
Ciliary Dyskinesia v1.58 DNAH8 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH8.
Source ClinGen was added to DNAH8.
Phenotypes for gene: DNAH8 were changed from Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, DNAH8-related
Publications for gene DNAH8 were changed from 24307375 to 24307375
Mendeliome v1.3393 DNAH8 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH8.
Source ClinGen was added to DNAH8.
Phenotypes for gene: DNAH8 were changed from Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MONDO:0033673; Primary ciliary dyskinesia, MONDO:0016575, DNAH8-related
Publications for gene DNAH8 were changed from 31178125, 32619401, 32681648, 33704367, 24307375 to 31178125, 32619401, 32681648, 33704367, 24307375
Fetal anomalies v1.441 DNAH8 Chirag Patel Phenotypes for gene: DNAH8 were changed from primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, DNAH8-related
Publications for gene DNAH8 were changed from 24307375 to 24307375
Infertility and Recurrent Pregnancy Loss v1.40 DNAH8 Chirag Patel Source Literature was removed from DNAH8.
Source ClinGen was added to DNAH8.
Phenotypes for gene: DNAH8 were changed from Spermatogenic failure 46, MIM# 619095 to Spermatogenic failure 46, MONDO:0033673
Publications for gene DNAH8 were changed from 31178125, 32619401, 32681648, 33704367 to 31178125, 32619401, 32681648, 33704367
Mendeliome v1.3392 DNAH1 Chirag Patel Classified gene: DNAH1 as Green List (high evidence)
Mendeliome v1.3392 DNAH1 Chirag Patel Gene: dnah1 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.57 DNAH1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH1.
Source ClinGen was added to DNAH1.
Phenotypes for gene: DNAH1 were changed from ?Ciliary dyskinesia, primary, 37 617577; Spermatogenic failure 18 617576 to Primary ciliary dyskinesia 7, MONDO:0012748
Publications for gene DNAH1 were changed from 25927852, 31765523, 33577779, 34210339 to 25927852, 31765523, 33577779, 34210339
Heterotaxy v1.43 DNAH1 Chirag Patel Phenotypes for gene: DNAH1 were changed from ?Ciliary dyskinesia, primary, 37 617577 to Primary ciliary dyskinesia 7, MONDO:0012748
Mendeliome v1.3391 DNAH1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNAH1.
Source ClinGen was added to DNAH1.
Phenotypes for gene: DNAH1 were changed from primary ciliary dyskinesia,37 MIM#617577; Spermatogenic failure 18 MIM#617576 to Spermatogenic failure 18, MONDO:0054615; Primary ciliary dyskinesia 7, MONDO:0012748
Publications for gene DNAH1 were changed from 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551, 25927852, 31765523, 33577779, 34210339 to 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551, 25927852, 31765523, 33577779, 34210339
Rating Changed from Green List (high evidence) to Red List (low evidence)
Infertility and Recurrent Pregnancy Loss v1.39 DNAH1 Chirag Patel Source Literature was removed from DNAH1.
Source ClinGen was added to DNAH1.
Phenotypes for gene: DNAH1 were changed from Spermatogenic failure 18 , MIM# 617576 to Spermatogenic failure 18, MONDO:0054615
Publications for gene DNAH1 were changed from 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551 to 34867808, 31507630, 24360805, 27798045, 11371505, 27798045, 29449551
Skeletal Dysplasia_Fetal v0.239 DHCR24 Chirag Patel Phenotypes for gene: DHCR24 were changed from Desmosterolosis - MIM#602398 to Desmosterolosis, MONDO:0011217
Skeletal dysplasia v0.338 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Miscellaneous Metabolic Disorders v1.55 DHCR24 Chirag Patel Phenotypes for gene: DHCR24 were changed from Desmosterolosis MIM#602398; Disorders of the metabolism of sterols to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Intellectual disability syndromic and non-syndromic v1.361 DHCR24 Chirag Patel Source Genetic Health Queensland was removed from DHCR24.
Source ClinGen was added to DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis, MIM# 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Fetal anomalies v1.440 DHCR24 Chirag Patel Source Genomics England PanelApp was removed from DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis, MIM# 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Genetic Epilepsy v1.250 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Source Australian Genomics Health Alliance Epilepsy Flagship was removed from DHCR24.
Source Victorian Clinical Genetics Services was removed from DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis, MIM# 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Callosome v0.562 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Source ClinGen was added to DHCR24.
Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Hydrocephalus_Ventriculomegaly v0.131 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Source ClinGen was added to DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis, MIM# 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Mendeliome v1.3390 DHCR24 Chirag Patel Source Victorian Clinical Genetics Services was removed from DHCR24.
Phenotypes for gene: DHCR24 were changed from Desmosterolosis MIM#602398; Disorders of the metabolism of sterols to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Arthrogryposis v0.427 DHCR24 Chirag Patel Phenotypes for gene: DHCR24 were changed from Desmosterolosis, MIM# 602398 to Desmosterolosis, MONDO:0011217
Publications for gene DHCR24 were changed from 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936 to 11519011, 33524375, 21671375, 12457401, 29175559, 21559050, 33027564, 38239854, 30891795, 25637936
Disorders of immune dysregulation v1.31 DEF6 Chirag Patel Phenotypes for gene: DEF6 were changed from Immunodeficiency 87 and autoimmunity, MIM# 619573; Systemic autoimmunity to Immunodeficiency 87 and autoimmunity, MONDO:0030457
Mendeliome v1.3389 DEF6 Chirag Patel Phenotypes for gene: DEF6 were changed from Immunodeficiency 87 and autoimmunity, MIM# 619573; Systemic autoimmunity to Immunodeficiency 87 and autoimmunity, MONDO:0030457
Intellectual disability syndromic and non-syndromic v1.360 DDX11 Chirag Patel Source Genetic Health Queensland was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Microcephaly v1.349 DDX11 Chirag Patel Source Literature was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Fetal anomalies v1.439 DDX11 Chirag Patel Source Genomics England PanelApp was removed from DDX11.
Source Literature was removed from DDX11.
Source Genetic Health Queensland was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Chromosome Breakage Disorders v1.24 DDX11 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Growth failure v1.83 DDX11 Chirag Patel Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Mendeliome v1.3388 DDX11 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDX11.
Source ClinGen was added to DDX11.
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM# 613398; MONDO:0013252 to Warsaw breakage syndrome, MONDO:0013252
Publications for gene DDX11 were changed from 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203 to 20137776, 23033317, 30216658, 30924321, 32855419, 36703504, 26089203
Hereditary Neuropathy - complex v1.35 DDHD1 Chirag Patel Source Royal Melbourne Hospital was removed from DDHD1.
Source ClinGen was added to DDHD1.
Phenotypes for gene: DDHD1 were changed from Spastic paraplegia, occasionally cerebellar eye signs and subclinical axonal neuropathy to Hereditary spastic paraplegia 28, MONDO:0012256
Publications for gene DDHD1 were changed from 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578 to 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578
Hereditary Spastic Paraplegia v1.100 DDHD1 Chirag Patel Phenotypes for gene: DDHD1 were changed from Spastic paraplegia 28, autosomal recessive, MIM# 609340; MONDO:0012256 to Hereditary spastic paraplegia 28, MONDO:0012256
Publications for gene DDHD1 were changed from 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578 to 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578
Mendeliome v1.3387 DDHD1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DDHD1.
Source ClinGen was added to DDHD1.
Phenotypes for gene: DDHD1 were changed from Spastic paraplegia 28, autosomal recessive, 609340; MONDO:0012256 to Hereditary spastic paraplegia 28, MONDO:0012256
Publications for gene DDHD1 were changed from 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578 to 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578
Hereditary Neuropathy - complex v1.34 DDHD1 Chirag Patel Classified gene: DDHD1 as Green List (high evidence)
Hereditary Neuropathy - complex v1.34 DDHD1 Chirag Patel Gene: ddhd1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.33 DDHD1 Chirag Patel reviewed gene: DDHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15786464, 23176821, 24989667, 27216551, 26944165, 28818478, 29980238, 27999540, 33600578; Phenotypes: Hereditary spastic paraplegia 28, MONDO:0012256; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.126 DCLRE1C Chirag Patel Source Victorian Clinical Genetics Services was removed from DCLRE1C.
Source Expert list was added to DCLRE1C.
Mode of inheritance for gene DCLRE1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCLRE1C were changed from to Severe combined immunodeficiency due to DCLRE1C deficiency, MONDO:0011225
Publications for gene DCLRE1C were changed from 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179 to 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179
Combined Immunodeficiency v1.135 DCLRE1C Chirag Patel Source Melbourne Genomics Health Alliance Immunology Flagship was removed from DCLRE1C.
Source Victorian Clinical Genetics Services was removed from DCLRE1C.
Source Expert list was added to DCLRE1C.
Phenotypes for gene: DCLRE1C were changed from Severe combined immunodeficiency, Athabascan type MIM# 602450; Omenn syndrome MIM# 603554 to Severe combined immunodeficiency due to DCLRE1C deficiency, MONDO:0011225
Publications for gene DCLRE1C were changed from 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179 to 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179
Mendeliome v1.3386 DCLRE1C Chirag Patel Source Victorian Clinical Genetics Services was removed from DCLRE1C.
Source Expert list was added to DCLRE1C.
Phenotypes for gene: DCLRE1C were changed from Severe combined immunodeficiency, Athabascan type MIM# 602450; Omenn syndrome, MIM# 603554 to Severe combined immunodeficiency due to DCLRE1C deficiency, MONDO:0011225
Publications for gene DCLRE1C were changed from 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179 to 12055248, 34220820, 11336668, 19953608, 15731174, 16540517, 18034425, 12504013, 15699179
Vasculitis v0.93 DCLRE1C Chirag Patel Classified gene: DCLRE1C as Red List (low evidence)
Vasculitis v0.93 DCLRE1C Chirag Patel Gene: dclre1c has been classified as Red List (Low Evidence).
Vasculitis v0.92 DCLRE1C Chirag Patel reviewed gene: DCLRE1C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3385 DCDC2 Chirag Patel Source Victorian Clinical Genetics Services was removed from DCDC2.
Source Victorian Clinical Genetics Services was removed from DCDC2.
Source Expert list was added to DCDC2.
Phenotypes for gene: DCDC2 were changed from Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394 to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394; Deafness, autosomal recessive 66, MIM# 610212
Mendeliome v1.3384 DBR1 Chirag Patel Publications for gene DBR1 were changed from 39023559, 29474921, 37656279 to 39023559, 29474921, 37656279
Genomic newborn screening: ICoNS v0.16 PAH Lilian Downie gene: PAH was added
gene: PAH was added to Genomic newborn screening: ICoNS. Sources: Expert list
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to PMID: 39630157; 40378670
Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600
Review for gene: PAH was set to GREEN
Added comment: Definitive gene disease association
Definitive for actionability in childhood
Included in traditional newborn screening in all jurisdictions
Sources: Expert list
Mendeliome v1.3383 DNM2 Chirag Patel Publications for gene DNM2 were changed from 15731758; 17636067; 33459893; 31628461; 23092955; 16227997; 33458580; 30232666; 24465259; 23938035 to 15731758; 17636067; 33459893; 31628461; 23092955; 16227997; 33458580; 30232666; 24465259; 23938035
Mendeliome v1.3382 MAFA Sangavi Sivagnanasundram gene: MAFA was added
gene: MAFA was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFA were set to 29339498
Phenotypes for gene: MAFA were set to Insulinomatosis and diabetes mellitus, OMIM #:147630
Review for gene: MAFA was set to GREEN
Added comment: Addition of this review to Mendeliome, was only on the hyperinsulinism panel

2 families with 36 individuals with AD inheritance of diabetes mellitus or insulinomatosis (adult-onset recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumours of pancreas). WES identified the same missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes in both families. The p.Ser64Phe mutation was found to impair phosphorylation within the transactivation domain of MAFA and profoundly increased MAFA protein stability under both high and low glucose concentrations in β-cell lines. In addition, the transactivation potential of p.Ser64Phe MAFA in β-cell lines was enhanced compared with wild-type MAFA. The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its key role in islet β-cell activity.
Sources: Other
Mendeliome v1.3382 DHX38 Arina Puzriakova changed review comment from: - PMID: 35719279 (2022) - another consanguineous family from Saudi Arabia with two sisters presented affected by retinitis pigmentosa since childhood. Whole exome sequencing identified a missense homozygous variant (c.2571C>T, p.(Ala857=)) in the DHX38 gene which segregated with the phenotype. No functional studies performed.

PMID: 37867960 (2023) - zebrafish knockout model shows a role in the development of the retina; to: - PMID: 35719279 (2022) - another consanguineous family from Saudi Arabia with two sisters presented affected by retinitis pigmentosa since childhood. Whole exome sequencing identified a missense homozygous variant (c.2571C>T, p.(Ala857=)) in the DHX38 gene which segregated with the phenotype. No functional studies performed.

- PMID: 37867960 (2023) - zebrafish knockout model shows a role in the development of the retina
Mendeliome v1.3382 DHX38 Arina Puzriakova reviewed gene: DHX38: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.359 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Intellectual disability syndromic and non-syndromic v1.358 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Genetic Epilepsy v1.249 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from to Congenital disorder of glycosylation, type IICC, MIM# 621381
Genetic Epilepsy v1.248 UGGT1 Zornitza Stark Publications for gene: UGGT1 were set to
Genetic Epilepsy v1.247 UGGT1 Zornitza Stark Mode of inheritance for gene: UGGT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.246 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Renal Macrocystic Disease v0.91 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Renal Macrocystic Disease v0.90 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Microcephaly v1.348 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Microcephaly v1.347 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Mendeliome v1.3382 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Mendeliome v1.3381 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Differences of Sex Development v1.23 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Differences of Sex Development v1.22 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Congenital Heart Defect v0.470 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Congenital Heart Defect v0.469 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Congenital Disorders of Glycosylation v1.77 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Congenital Disorders of Glycosylation v1.76 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Autism v0.223 UGGT1 Zornitza Stark Marked gene: UGGT1 as ready
Autism v0.223 UGGT1 Zornitza Stark Gene: uggt1 has been classified as Green List (High Evidence).
Autism v0.223 UGGT1 Zornitza Stark Phenotypes for gene: UGGT1 were changed from Congenital disorder of glycosylation - MONDO:0015286; UGGT1-CDG to Congenital disorder of glycosylation, type IICC, MIM# 621381
Autism v0.222 UGGT1 Zornitza Stark reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IICC, MIM# 621381; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v1.358 NAA20 Chern Lim reviewed gene: NAA20: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37191084; Phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Infertility and Recurrent Pregnancy Loss v1.38 INCENP Rylee Peters gene: INCENP was added
gene: INCENP was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: INCENP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INCENP were set to 41005306
Phenotypes for gene: INCENP were set to Oocyte/zygote/embryo maturation arrest MONDO:0014769, INCENP-related
Review for gene: INCENP was set to AMBER
Added comment: 3 unrelated women presenting with abnormal oocyte morphology and/or low fertilisation rate from a large cohort of 3627 individuals. WES identified biallelic missense variants:
R267Q (gnomAD v4: 1717 hets, 12 homs), R280W (5 hets, 0 homs), P444L (207 hets, 0 homs), R693W (686 hets, 1 hom), K816T (110 hets, 1 hom), K890E (3 hets, 0 homs).

siRNA-mediated knock-down of INCENP in mouse oocytes reduced polar-body extrusion rates, demonstrating that loss of function of the protein affects oocyte maturation.
Sources: Literature
Mendeliome v1.3381 INCENP Rylee Peters gene: INCENP was added
gene: INCENP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: INCENP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INCENP were set to 41005306
Phenotypes for gene: INCENP were set to Oocyte/zygote/embryo maturation arrest MONDO:0014769, INCENP-related
Review for gene: INCENP was set to AMBER
Added comment: 3 unrelated women presenting with abnormal oocyte morphology and/or low fertilisation rate from a large cohort of 3627 individuals. WES identified biallelic missense variants:
R267Q (gnomAD v4: 1717 hets, 12 homs), R280W (5 hets, 0 homs), P444L (207 hets, 0 homs), R693W (686 hets, 1 hom), K816T (110 hets, 1 hom), K890E (3 hets, 0 homs).

siRNA-mediated knock-down of INCENP in mouse oocytes reduced polar-body extrusion rates, demonstrating that loss of function of the protein affects oocyte maturation.
Sources: Literature
Mendeliome v1.3381 ANKRD24 Rylee Peters reviewed gene: ANKRD24: Rating: RED; Mode of pathogenicity: None; Publications: 40989574; Phenotypes: Sensorineural hearing loss disorder MONDO:0020678, ANKRD24-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.361 SWSAP1 Rylee Peters gene: SWSAP1 was added
gene: SWSAP1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: SWSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SWSAP1 were set to 40991243
Phenotypes for gene: SWSAP1 were set to Primary ovarian insufficiency, MONDO:0005387, SWSAP1-related
Review for gene: SWSAP1 was set to RED
Added comment: Cohort with severe isolated premature ovarian insufficiency. 1x individual homozygous for a frameshift SWSAP1 variant, c.353del, p.(Gly118AlafsTer2), absent from gnomAD v4.

Functional: western-blot indicates reduced stability of the truncated protein; the truncated SWSAP1 variant fails to complement the IH-HR (interhomolog homologous recombination) defect of Swsap1−/− cells (undetected IH-HR activity).
Sources: Literature
Mendeliome v1.3381 SWSAP1 Rylee Peters gene: SWSAP1 was added
gene: SWSAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SWSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SWSAP1 were set to 40991243
Phenotypes for gene: SWSAP1 were set to Primary ovarian insufficiency, MONDO:0005387, SWSAP1-related
Review for gene: SWSAP1 was set to RED
Added comment: Cohort with severe isolated premature ovarian insufficiency. 1x individual homozygous for a frameshift SWSAP1 variant, c.353del, p.(Gly118AlafsTer2), absent from gnomAD v4.

Functional: western-blot indicates reduced stability of the truncated protein; the truncated SWSAP1 variant fails to complement the IH-HR (interhomolog homologous recombination) defect of Swsap1−/− cells (undetected IH-HR activity).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v1.38 FSIP2 Rylee Peters gene: FSIP2 was added
gene: FSIP2 was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FSIP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSIP2 were set to 30137358; 40968718; 36632462; 33631238
Phenotypes for gene: FSIP2 were set to Spermatogenic failure 34, MIM#618153
Review for gene: FSIP2 was set to GREEN
Added comment: Multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF) carrying biallelic variants.
Sources: Literature
Mendeliome v1.3381 FSIP2 Rylee Peters gene: FSIP2 was added
gene: FSIP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FSIP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSIP2 were set to 30137358; 40968718; 36632462; 33631238
Phenotypes for gene: FSIP2 were set to Spermatogenic failure 34, MIM#618153
Review for gene: FSIP2 was set to GREEN
Added comment: Multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF) carrying biallelic variants.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.130 AMOT Rylee Peters gene: AMOT was added
gene: AMOT was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: AMOT was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AMOT were set to 40892511
Phenotypes for gene: AMOT were set to Congenital hydrocephalus MONDO:0016349, AMOT-related
Review for gene: AMOT was set to AMBER
Added comment: 1x family with isolated X-linked congenital hydrocephalus – clinical presentation considered late, identified in the third trimester. Variant segregated with disease in 6x affected hemizygous males (4x live-born and 2x terminated male fetuses). Carrier females are apparently normal (no brain MRI was performed).

Exome sequencing identified start loss variant, c.2T>C p.(Met1Thr). Functional analyses identify that the variant results in a protein lacking 91 amino acids from the N-terminus and leads to abnormally increased AMOT protein levels (increased stability due to loss of degradation signals), which disrupts epithelial and endothelial barrier integrity.
Sources: Literature
Fetal anomalies v1.438 AMOT Rylee Peters gene: AMOT was added
gene: AMOT was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AMOT was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AMOT were set to 40892511
Phenotypes for gene: AMOT were set to Congenital hydrocephalus MONDO:0016349, AMOT-related
Review for gene: AMOT was set to AMBER
Added comment: 1x family with isolated X-linked congenital hydrocephalus – clinical presentation considered late, identified in the third trimester. Variant segregated with disease in 6x affected hemizygous males (4x live-born and 2x terminated male fetuses). Carrier females are apparently normal (no brain MRI was performed).

Exome sequencing identified start loss variant, c.2T>C p.(Met1Thr). Functional analyses identify that the variant results in a protein lacking 91 amino acids from the N-terminus and leads to abnormally increased AMOT protein levels (increased stability due to loss of degradation signals), which disrupts epithelial and endothelial barrier integrity.
Sources: Literature
Mendeliome v1.3381 AMOT Rylee Peters gene: AMOT was added
gene: AMOT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMOT was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AMOT were set to 40892511
Phenotypes for gene: AMOT were set to Congenital hydrocephalus MONDO:0016349, AMOT-related
Review for gene: AMOT was set to AMBER
Added comment: 1x family with isolated X-linked congenital hydrocephalus – clinical presentation considered late, identified in the third trimester. Variant segregated with disease in 6x affected hemizygous males (4x live-born and 2x terminated male fetuses). Carrier females are apparently normal (no brain MRI was performed).

Exome sequencing identified start loss variant, c.2T>C p.(Met1Thr). Functional analyses identify that the variant results in a protein lacking 91 amino acids from the N-terminus and leads to abnormally increased AMOT protein levels (increased stability due to loss of degradation signals), which disrupts epithelial and endothelial barrier integrity.
Sources: Literature
Mendeliome v1.3381 HECTD4 Elena Savva reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28191890, 31981491, 31785789; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.246 MDGA2 Sangavi Sivagnanasundram gene: MDGA2 was added
gene: MDGA2 was added to Genetic Epilepsy. Sources: Other
Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760
Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092
Review for gene: MDGA2 was set to GREEN
Added comment: Affected individuals present with a broad neurodevelopmental impairment-like phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other
Mendeliome v1.3381 MDGA2 Sangavi Sivagnanasundram changed review comment from: Affected individuals present with a broad neurodevelopmental impairment phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other; to: Affected individuals present with a broad neurodevelopmental impairment-like phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other
Mendeliome v1.3381 MDGA2 Sangavi Sivagnanasundram gene: MDGA2 was added
gene: MDGA2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760
Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092
Review for gene: MDGA2 was set to GREEN
Added comment: Affected individuals present with a broad neurodevelopmental impairment phenotype.

Pre-print - https://doi.org/10.1101/2025.08.28.25330873
Individuals with developmental and epileptic encephalopathy (DEE)
8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features.
7 different biallelic LoF variants were identified
p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1
In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism.

PMID: 40168357, 27608760
A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment).
The mice also showed abnormalities in excitatory synapses.
Sources: Other
Mendeliome v1.3381 CACNB1 Sangavi Sivagnanasundram reviewed gene: CACNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 41023410; Phenotypes: Congenital muscular dystrophy MONDO:0020121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.438 ATP5O Bryony Thompson Tag new gene name tag was added to gene: ATP5O.
Intellectual disability syndromic and non-syndromic v1.358 ATP5O Bryony Thompson Tag new gene name tag was added to gene: ATP5O.
Mitochondrial disease v0.1083 ATP5O Bryony Thompson Tag new gene name tag was added to gene: ATP5O.
Mendeliome v1.3381 ATP5O Bryony Thompson Tag new gene name tag was added to gene: ATP5O.
Infertility and Recurrent Pregnancy Loss v1.38 DDOST Bryony Thompson Marked gene: DDOST as ready
Infertility and Recurrent Pregnancy Loss v1.38 DDOST Bryony Thompson Gene: ddost has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.38 DDOST Bryony Thompson Classified gene: DDOST as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v1.38 DDOST Bryony Thompson Gene: ddost has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v1.37 DDOST Bryony Thompson gene: DDOST was added
gene: DDOST was added to Infertility and Recurrent Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DDOST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDOST were set to 41005306
Phenotypes for gene: DDOST were set to inherited oocyte maturation defect MONDO:0014769
Review for gene: DDOST was set to AMBER
Added comment: 3 cases with embryonic arrest/abnormal fertilisation with biallelic DDOST variants (1 homozygous & 2 chets, phase not confirmed). No mention of any other phenotypes or assessment of transferrin glycolysation status in cases. Unsure if cases have DDOST-CDG. DDOST knock‑down in mouse oocytes reduces polar‑body extrusion & mutant DDOST proteins displayed altered subcellular localization in HeLa cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.358 DDOST Bryony Thompson Phenotypes for gene: DDOST were changed from Congenital disorder of glycosylation, type Ir, MIM# 614507 to DDOST-congenital disorder of glycosylation MONDO:0013789
Intellectual disability syndromic and non-syndromic v1.357 DDOST Bryony Thompson Publications for gene: DDOST were set to 22305527
Intellectual disability syndromic and non-syndromic v1.356 DDOST Bryony Thompson Classified gene: DDOST as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.356 DDOST Bryony Thompson Gene: ddost has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.355 DDOST Bryony Thompson Classified gene: DDOST as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.355 DDOST Bryony Thompson Gene: ddost has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.354 DDOST Bryony Thompson edited their review of gene: DDOST: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v1.354 DDOST Bryony Thompson reviewed gene: DDOST: Rating: ; Mode of pathogenicity: None; Publications: 22305527, 34462534, 36214423, 37848450, 33413482, 36631682; Phenotypes: DDOST-congenital disorder of glycosylation MONDO:0013789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.76 DDOST Bryony Thompson Phenotypes for gene: DDOST were changed from Congenital disorder of glycosylation, type Ir, MIM# 614507 to DDOST-congenital disorder of glycosylation MONDO:0013789
Congenital Disorders of Glycosylation v1.75 DDOST Bryony Thompson Classified gene: DDOST as Green List (high evidence)
Congenital Disorders of Glycosylation v1.75 DDOST Bryony Thompson Gene: ddost has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.74 DDOST Bryony Thompson reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305527, 34462534, 36214423, 37848450, 33413482, 36631682; Phenotypes: DDOST-congenital disorder of glycosylation MONDO:0013789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3381 DDOST Bryony Thompson Phenotypes for gene: DDOST were changed from Congenital disorder of glycosylation, type Ir, MIM# 614507 to DDOST-congenital disorder of glycosylation MONDO:0013789; inherited oocyte maturation defect MONDO:0014769
Mendeliome v1.3380 DDOST Bryony Thompson Publications for gene: DDOST were set to 22305527
Mendeliome v1.3379 DDOST Bryony Thompson Classified gene: DDOST as Green List (high evidence)
Mendeliome v1.3379 DDOST Bryony Thompson Gene: ddost has been classified as Green List (High Evidence).
Mendeliome v1.3378 DDOST Bryony Thompson reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305527, 34462534, 36214423, 37848450, 33413482, 36631682, 41005306; Phenotypes: DDOST-congenital disorder of glycosylation MONDO:0013789, inherited oocyte maturation defect MONDO:0014769; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.246 RNU4-2 Chirag Patel Classified gene: RNU4-2 as Green List (high evidence)
Genetic Epilepsy v1.246 RNU4-2 Chirag Patel Gene: rnu4-2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.245 RNU4-2 Chirag Patel gene: RNU4-2 was added
gene: RNU4-2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38991538
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Review for gene: RNU4-2 was set to GREEN
Added comment: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES. Epilepsy seen in 50% cases.
Sources: Expert list
Mendeliome v1.3378 MIA3 Sangavi Sivagnanasundram reviewed gene: MIA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40948380, 40119123; Phenotypes: odontochondrodysplasia MONDO:0031169; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.469 RYR3 Bryony Thompson Marked gene: RYR3 as ready
Congenital Heart Defect v0.469 RYR3 Bryony Thompson Gene: ryr3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.469 RYR3 Bryony Thompson Classified gene: RYR3 as Green List (high evidence)
Congenital Heart Defect v0.469 RYR3 Bryony Thompson Gene: ryr3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.468 RYR3 Bryony Thompson gene: RYR3 was added
gene: RYR3 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: RYR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RYR3 were set to 39762984; 41022857
Phenotypes for gene: RYR3 were set to congenital heart disease MONDO:0005453
Review for gene: RYR3 was set to GREEN
Added comment: Congenital heart disease - at least 4 rare de novo missense and a supporting knockout zebrafish model
PMID: 39762984 - a proband with CHD phenotype (Duodenal atresia, Ventricular septal defect, Secundum atrial septal defect, Tricuspid valve prolapse, Vesicoureteral reflux) with a de novo stopgain variant (c.12295G>T). Zebrafish knockout shows enlarged atria and ventricle, matching patient phenotype
PMID: 41022857 - 4 de novo missense (L110I, S2130L, Y2743C, F2957L - Y2743C has a homozygote & AF in gnomAD higher than expected for AD disease - AF=0.0002760) identified in a CHD cohort
Sources: Literature
Mendeliome v1.3378 RYR3 Bryony Thompson Classified gene: RYR3 as Green List (high evidence)
Mendeliome v1.3378 RYR3 Bryony Thompson Gene: ryr3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.244 RYR3 Bryony Thompson Publications for gene: RYR3 were set to 25262651
Genetic Epilepsy v1.243 RYR3 Bryony Thompson Classified gene: RYR3 as Amber List (moderate evidence)
Genetic Epilepsy v1.243 RYR3 Bryony Thompson Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.242 RYR3 Bryony Thompson edited their review of gene: RYR3: Added comment: Epilepsy - mild to severe phenotypes reported with both de novo heterozygous (3) and biallelic (7). However, no supporting functional evidence for a gene-disease association
PMID: 39840699
Families: 7 families (7 unrelated)
Patients: 7 patients
Phenotype: partial seizures, febrile seizures, normal brain MRI
Mode of inheritance: Monoallelic and biallelic (1 de novo heterozygous; 6 compound heterozygous inherited from asymptomatic parents)
Variants: c.12947A>G (missense); c.2747A>C (missense); c.12514G>A (missense); c.3697G>A (missense); c.9994A>G (missense); c.4936G>A (missense); c.10859G>T (missense); c.9917A>G (missense); c.12463G>A (missense); c.11386G>C (missense); c.13690G>C (missense); c.11798C>G (missense); c.13363G>A (missense)
Population Frequency: gnomAD: 0–0.00022 (overall); up to 0.0031 in East Asian controls
Functional: protein modeling (I‑TASSER, PyMOL) and stability predictions (I‑Mutant)
PMID: 39220738, 25262651, 29667327
Families: 4 families (4 unrelated)
Patients: 4 patients
Phenotype: infantile spasm syndrome, developmental regression, multifocal EEG discharges, intractable seizures
Mode of inheritance: Monoallelic (de novo heterozygous; also 1 AR compound heterozygote reported); Changed publications: 25262651, 39840699, 39220738, 29667327; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.3377 RYR3 Bryony Thompson Phenotypes for gene: RYR3 were changed from Congenital myopathy 20, MIM# 620310; developmental and epileptic encephalopathy (MONDO:0100062) to congenital heart disease MONDO:0005453; Congenital myopathy 20, MIM# 620310; developmental and epileptic encephalopathy (MONDO:0100062)
Mendeliome v1.3376 RYR3 Bryony Thompson Publications for gene: RYR3 were set to 29498452; 32451403; 31230720; 25262651
Mendeliome v1.3375 RYR3 Bryony Thompson reviewed gene: RYR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 39762984, 41022857, 39840699, 39220738, 25262651, 29667327; Phenotypes: congenital heart disease MONDO:0005453, developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.467 ZDHHC18 Bryony Thompson Classified gene: ZDHHC18 as Amber List (moderate evidence)
Congenital Heart Defect v0.467 ZDHHC18 Bryony Thompson Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.466 ZDHHC18 Bryony Thompson gene: ZDHHC18 was added
gene: ZDHHC18 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: ZDHHC18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZDHHC18 were set to 41022857
Phenotypes for gene: ZDHHC18 were set to congenital heart disease MONDO:0005453
Review for gene: ZDHHC18 was set to AMBER
Added comment: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort. No functional assays conducted.
Sources: Literature
Mendeliome v1.3375 ZDHHC18 Bryony Thompson Classified gene: ZDHHC18 as Amber List (moderate evidence)
Mendeliome v1.3375 ZDHHC18 Bryony Thompson Gene: zdhhc18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3374 ZDHHC18 Bryony Thompson changed review comment from: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort.
Sources: Literature; to: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort. No functional assays conducted.
Sources: Literature
Mendeliome v1.3374 ZDHHC18 Bryony Thompson gene: ZDHHC18 was added
gene: ZDHHC18 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZDHHC18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZDHHC18 were set to 41022857
Phenotypes for gene: ZDHHC18 were set to congenital heart disease MONDO:0005453
Review for gene: ZDHHC18 was set to AMBER
Added comment: ZDHHC18 appears among significant CHD genes in the de novo enrichment analysis. Two de novo missense variants (W290L, G297A) were identified in 2 probands via trio analysis in a CHD cohort.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.354 TM2D3 Zornitza Stark Phenotypes for gene: TM2D3 were changed from Neurodevelopmental disorder, MONDO:0700092, TM2D3-related to Neurocardiorenal malformation syndrome, MIM# 621379
Intellectual disability syndromic and non-syndromic v1.353 TM2D3 Zornitza Stark edited their review of gene: TM2D3: Changed phenotypes: Neurocardiorenal malformation syndrome, MIM# 621379
Microcephaly v1.347 TM2D3 Zornitza Stark Phenotypes for gene: TM2D3 were changed from Neurodevelopmental disorder, MONDO:0700092, TM2D3-related to Neurocardiorenal malformation syndrome, MIM# 621379
Microcephaly v1.346 TM2D3 Zornitza Stark edited their review of gene: TM2D3: Changed phenotypes: Neurocardiorenal malformation syndrome, MIM# 621379
Mendeliome v1.3373 TM2D3 Zornitza Stark Phenotypes for gene: TM2D3 were changed from Neurodevelopmental disorder, MONDO:0700092, TM2D3-related to Neurocardiorenal malformation syndrome, MIM# 621379
Mendeliome v1.3372 TM2D3 Zornitza Stark edited their review of gene: TM2D3: Changed phenotypes: Neurocardiorenal malformation syndrome, MIM# 621379
Intellectual disability syndromic and non-syndromic v1.353 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related to Harel-Tora neurodevelopmental syndrome, MIM# 621377
Intellectual disability syndromic and non-syndromic v1.352 ATXN7L3 Zornitza Stark reviewed gene: ATXN7L3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Harel-Tora neurodevelopmental syndrome, MIM# 621377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3372 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related to Harel-Tora neurodevelopmental syndrome, MIM# 621377
Mendeliome v1.3371 ATXN7L3 Zornitza Stark reviewed gene: ATXN7L3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Harel-Tora neurodevelopmental syndrome, MIM# 621377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3371 NAMPT Bryony Thompson Marked gene: NAMPT as ready
Mendeliome v1.3371 NAMPT Bryony Thompson Gene: nampt has been classified as Red List (Low Evidence).
Mendeliome v1.3371 NAMPT Bryony Thompson gene: NAMPT was added
gene: NAMPT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAMPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAMPT were set to 41004591
Phenotypes for gene: NAMPT were set to hereditary motor and sensory neuropathy MONDO:0015358
Review for gene: NAMPT was set to RED
Added comment: A single family reported.
Disease Context: sensory and motor neuropathy with motor coordination impairment, muscle atrophy/weakness, foot/hand deformities, loss of sensation and positive Babinski sign
Families: 1 family
Patients: 2
Phenotype: impaired motor coordination, muscle atrophy/weakness, foot and hand deformities, diminished sensation, positive Babinski sign
Mode of inheritance: Biallelic (autosomal recessive; parents heterozygous carriers, affected siblings homozygous). No mention of consanguinity
Variants: c.472G>C (p.P158A) (missense)
Population Frequency: gnomAD: 0
Segregation: parents heterozygous, both affected siblings homozygous (pedigree confirmed)
Functional Studies: recombinant NAMPT protein activity assay; thermal shift stability assay; patient fibroblast bioenergetic, mitochondrial and oxidative stress assays; CRISPR‑generated isogenic fibroblasts; homozygous p.P158A mouse model showing metabolic, synaptic and motor neuron defects; rescue with NMN/P7C3
Prior Reports: none.
Sources: Literature
Mendeliome v1.3370 DBX1 Bryony Thompson Marked gene: DBX1 as ready
Mendeliome v1.3370 DBX1 Bryony Thompson Gene: dbx1 has been classified as Red List (Low Evidence).
Mendeliome v1.3370 DBX1 Bryony Thompson gene: DBX1 was added
gene: DBX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DBX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBX1 were set to 40995053
Phenotypes for gene: DBX1 were set to central hypoventilation syndrome, congenital MONDO:0800031
Review for gene: DBX1 was set to RED
Added comment: Disease Context: Congenital central hypoventilation syndrome (atypical CCHS) with central hypotonia, global developmental delay, seizures, autoaggressive behavior
Families: 1 (1 unrelated)
Patients: 1
Phenotype: congenital central hypoventilation, central hypotonia, global developmental delay, seizures, autoaggressive behavior
Mode of inheritance: Biallelic (consanguineous parents (first cousins))
Variants: c.340_341delGC (frameshift)
Population Frequency: NR
Segregation: NR
Functional Studies: mouse Dbx1 knockout lethality indicating essential role in respiration
Prior Reports: 0
Sources: Literature
Retinitis pigmentosa v0.179 TRIM49 Bryony Thompson Marked gene: TRIM49 as ready
Retinitis pigmentosa v0.179 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3369 TRIM49 Bryony Thompson Marked gene: TRIM49 as ready
Mendeliome v1.3369 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3369 TRIM49 Bryony Thompson Classified gene: TRIM49 as Amber List (moderate evidence)
Mendeliome v1.3369 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v0.179 TRIM49 Bryony Thompson Classified gene: TRIM49 as Amber List (moderate evidence)
Retinitis pigmentosa v0.179 TRIM49 Bryony Thompson Gene: trim49 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3368 TRIM49 Bryony Thompson changed review comment from: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature; to: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not. This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature
Retinitis pigmentosa v0.178 TRIM49 Bryony Thompson gene: TRIM49 was added
gene: TRIM49 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: TRIM49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM49 were set to 40956390
Phenotypes for gene: TRIM49 were set to retinitis pigmentosa MONDO:0019200
Review for gene: TRIM49 was set to AMBER
Added comment: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not. This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature
Mendeliome v1.3368 TRIM49 Bryony Thompson gene: TRIM49 was added
gene: TRIM49 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM49 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM49 were set to 40956390
Phenotypes for gene: TRIM49 were set to retinitis pigmentosa MONDO:0019200
Review for gene: TRIM49 was set to AMBER
Added comment: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families.
Sources: Literature
Mendeliome v1.3367 PCDHA9 Bryony Thompson Marked gene: PCDHA9 as ready
Mendeliome v1.3367 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Red List (Low Evidence).
Mendeliome v1.3367 PCDHA9 Bryony Thompson gene: PCDHA9 was added
gene: PCDHA9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHA9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCDHA9 were set to 29477871; 40988636
Phenotypes for gene: PCDHA9 were set to Hirschsprung disease MONDO:0018309; root resorption MONDO:0001997
Review for gene: PCDHA9 was set to RED
Added comment: Single publication reporting an association with Hirschsprung disease, including a missense in a family (p.Gly572Arg) that is too common in gnomAD to be associated with disease and 2 rare missense in 2 sporadic cases. Knockdown in a cell line increased proliferation and
migration, but suppressed apoptosis. A single publication with a single missense reported in association with short root anomaly.
Sources: Literature
Incidentalome v0.349 PCDHA9 Bryony Thompson Marked gene: PCDHA9 as ready
Incidentalome v0.349 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.349 PCDHA9 Bryony Thompson Classified gene: PCDHA9 as Amber List (moderate evidence)
Incidentalome v0.349 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.38 PCDHA9 Bryony Thompson Marked gene: PCDHA9 as ready
Motor Neurone Disease v1.38 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.38 PCDHA9 Bryony Thompson Classified gene: PCDHA9 as Amber List (moderate evidence)
Motor Neurone Disease v1.38 PCDHA9 Bryony Thompson Gene: pcdha9 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.348 PCDHA9 Bryony Thompson gene: PCDHA9 was added
gene: PCDHA9 was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: PCDHA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHA9 were set to 38467605
Phenotypes for gene: PCDHA9 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: PCDHA9 was set to AMBER
Added comment: Three unrelated families (one consanguineous and 2 living in close proximity) carry a homozygous c.2099T>C (p.Leu700Pro) missense variant in the transmembrane domain of PCDHA9; detailed clinical data: age at onset 36‑42 yr, limb weakness, UMN/LMN signs, EMG abnormalities, disease duration <4 yr; the variant is rare (gnomAD East Asian MAF≈0.00022, no homozygotes) and absent in 392 ALS controls; functional studies (mouse knock‑in and deletion models, HEK293 protein‑stability assays) demonstrate loss‑of‑function effects supporting pathogenicity.
Sources: Literature
Motor Neurone Disease v1.37 PCDHA9 Bryony Thompson gene: PCDHA9 was added
gene: PCDHA9 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: PCDHA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHA9 were set to 38467605
Phenotypes for gene: PCDHA9 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: PCDHA9 was set to AMBER
Added comment: Three unrelated families (one consanguineous and 2 living in close proximity) carry a homozygous c.2099T>C (p.Leu700Pro) missense variant in the transmembrane domain of PCDHA9; detailed clinical data: age at onset 36‑42 yr, limb weakness, UMN/LMN signs, EMG abnormalities, disease duration <4 yr; the variant is rare (gnomAD East Asian MAF≈0.00022, no homozygotes) and absent in 392 ALS controls; functional studies (mouse knock‑in and deletion models, HEK293 protein‑stability assays) demonstrate loss‑of‑function effects supporting pathogenicity.
Sources: Literature
Genetic Epilepsy v1.242 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Red List (low evidence)
Genetic Epilepsy v1.242 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Marked gene: RNU6ATAC as ready
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Red List (low evidence)
Mendeliome v1.3366 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Microcephaly v1.346 RNU6ATAC Zornitza Stark Marked gene: RNU6ATAC as ready
Microcephaly v1.346 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Microcephaly v1.346 RNU6ATAC Zornitza Stark Classified gene: RNU6ATAC as Red List (low evidence)
Microcephaly v1.346 RNU6ATAC Zornitza Stark Gene: rnu6atac has been classified as Red List (Low Evidence).
Microcephaly v1.345 RNU6ATAC Zornitza Stark reviewed gene: RNU6ATAC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3365 HYPK Zornitza Stark Publications for gene: HYPK were set to Clinical Genetics Early View
Intellectual disability syndromic and non-syndromic v1.352 HYPK Zornitza Stark Publications for gene: HYPK were set to Clinical Genetics Early View
Mendeliome v1.3364 DNAH14 Zornitza Stark reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.3364 TLN1 Zornitza Stark Publications for gene: TLN1 were set to 30888838; 35861643
Bleeding and Platelet Disorders v1.62 TLN1 Zornitza Stark Publications for gene: TLN1 were set to 35861643
Bleeding and Platelet Disorders v1.61 TLN1 Zornitza Stark Classified gene: TLN1 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.61 TLN1 Zornitza Stark Gene: tln1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3363 BCAT1 Zornitza Stark Marked gene: BCAT1 as ready
Mendeliome v1.3363 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Mendeliome v1.3363 BCAT1 Zornitza Stark Classified gene: BCAT1 as Red List (low evidence)
Mendeliome v1.3363 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.351 BCAT1 Zornitza Stark Marked gene: BCAT1 as ready
Intellectual disability syndromic and non-syndromic v1.351 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.351 BCAT1 Zornitza Stark Classified gene: BCAT1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.351 BCAT1 Zornitza Stark Gene: bcat1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.350 BCAT1 Lucy Spencer gene: BCAT1 was added
gene: BCAT1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BCAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCAT1 were set to 41029903
Phenotypes for gene: BCAT1 were set to Neurodevelopmental disorder (MONDO:0700092), BCAT1-related
Review for gene: BCAT1 was set to RED
Added comment: PMID: 41029903 One patient with a suspected neurometabolic disorder; congenital blindness and suspected Leber Congenital Amaurosis, microcephaly, failure to thrive, profound global developmental delay and extensive delayed myelination on MRI. AT 10 he was non-verbal and non-ambulatory with regression of motor skills and -3SD for height and weight. Compound heterozygous for Phe264Leu (539 hets but no homs in gnomad v4) and Glu348Lys (over 8000 hets and 24 homs in gnomad v4).

in compound heterozygous iPSCs a severe 75% reduction in BCAT1 protein levels was seen, but mRNA levels were normal suggesting the variants affect protein stability or increased degradation.
Sources: Literature
Mendeliome v1.3362 BCAT1 Lucy Spencer gene: BCAT1 was added
gene: BCAT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BCAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCAT1 were set to 41029903
Phenotypes for gene: BCAT1 were set to Neurodevelopmental disorder (MONDO:0700092), BCAT1-related
Review for gene: BCAT1 was set to RED
Added comment: PMID: 41029903 One patient with a suspected neurometabolic disorder; congenital blindness and suspected Leber Congenital Amaurosis, microcephaly, failure to thrive, profound global developmental delay and extensive delayed myelination on MRI. AT 10 he was non-verbal and non-ambulatory with regression of motor skills and -3SD for height and weight. Compound heterozygous for Phe264Leu (539 hets but no homs in gnomad v4) and Glu348Lys (over 8000 hets and 24 homs in gnomad v4).

in compound heterozygous iPSCs a severe 75% reduction in BCAT1 protein levels was seen, but mRNA levels were normal suggesting the variants affect protein stability or increased degradation.
Sources: Literature
Bleeding and Platelet Disorders v1.60 TLN1 Lucy Spencer reviewed gene: TLN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 40960860; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3362 TLN1 Lucy Spencer edited their review of gene: TLN1: Added comment: PMID: 40960860 de novo L353F identified in a patient with increased nuchal translucency, leukopenia, thrombocytopenia, congenital cataracts, multiple episodes of acute bronchitis, skin lesions and swelling after exercise in cold weather. Overlapping authors with PMID: 35861643, and they are postulating this is a 2nd case of the condition reported there. Some functional studies showing decreased thermal stability, has slower cellular migration and that it was slightly more aggregation-prone than WT.

Shared symptoms between both patients; leukopenia, thrombocytopenia, congenital cataract, and recurring episodes of acute bronchitis. Both mutations situated in the talin-1 head F2F3 domains and both have been shown to have defects in cellular migration and integrin activation.; Changed rating: AMBER; Changed publications: 40960860; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3362 TLN1 Lucy Spencer reviewed gene: TLN1: Rating: RED; Mode of pathogenicity: None; Publications: 39704176; Phenotypes: Capillary leak syndrome MONDO:0001956, TLN1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.3362 DNAH14 Lucy Spencer reviewed gene: DNAH14: Rating: AMBER; Mode of pathogenicity: None; Publications: 36344539, 41002930; Phenotypes: Neurodevelopmental disorder MONDO:0700092, DNAH14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Transplant Co-Morbidity v0.20 Bryony Thompson Panel name changed from Transplant Co-Morbidity Superpanel to Transplant Co-Morbidity
Intellectual disability syndromic and non-syndromic v1.350 HYPK Sangavi Sivagnanasundram reviewed gene: HYPK: Rating: ; Mode of pathogenicity: None; Publications: 40986405; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, HYPK-related; Mode of inheritance: None
Mendeliome v1.3362 HYPK Sangavi Sivagnanasundram reviewed gene: HYPK: Rating: ; Mode of pathogenicity: None; Publications: 40986405; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, HYPK-related; Mode of inheritance: None
Microcephaly v1.345 RNU6ATAC Lucy Spencer gene: RNU6ATAC was added
gene: RNU6ATAC was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 40975062
Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Review for gene: RNU6ATAC was set to AMBER
Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: Literature
Genetic Epilepsy v1.241 RNU6ATAC Lucy Spencer gene: RNU6ATAC was added
gene: RNU6ATAC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 40975062
Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Review for gene: RNU6ATAC was set to RED
Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.350 RNU6ATAC Lucy Spencer gene: RNU6ATAC was added
gene: RNU6ATAC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 40975062
Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Review for gene: RNU6ATAC was set to RED
Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: Literature
Mendeliome v1.3362 RNU6ATAC Lucy Spencer gene: RNU6ATAC was added
gene: RNU6ATAC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to 40975062
Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Review for gene: RNU6ATAC was set to RED
Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: Literature
Mendeliome v1.3362 NFXL1 Lucy Spencer gene: NFXL1 was added
gene: NFXL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFXL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFXL1 were set to 40430072; 41024252
Phenotypes for gene: NFXL1 were set to Syndromic disease (MONDO:0002254), NFXL1-related
Review for gene: NFXL1 was set to AMBER
Added comment: PMID: 40430072 2 siblings with psychosis and schizophrenia, homozygous for Cys441Tyr. Some modelling suggested a deleterious affect but no functional studies performed.

PMID: 41024252 8 patients from 7 families with joint hyperlaxity, with or without short stature and renal disease. 6 families were homozygous for p.(Cys539Trpfs*64) while the other two were homozygous for p.(Lys681*). Paper described both as founder variants but they are rare/absent in gnomad.

Joint hyperlaxity (7), chronic kidney disease/FSGS (2) small echogenic kidneys (3), acute kidney injury (1), dysmorphic features (6), short stature (6), speech delay (3).

One patient also had epilepsy, developmental delay and spasticity however c.728+1G>A in WDR45 explained this part of her phenotype. Other patients also had more severe outlying symptoms with no other explanation mentioned: 1 with developmental delay, hearing loss, brain malformations, skeletal abnormalities, and another a 3 year old who passed away following a complex medical course including blue sclera, proximal tibial fracture, severe respiratory distress due to a chest infection, and acute kidney injury.

Amber given the variable phenotype findings of the reported patients and only 2 homozygous variants identified so far
Sources: Literature
Fetal anomalies v1.438 PTBP1 Lucy Spencer gene: PTBP1 was added
gene: PTBP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP1 were set to 40965981
Phenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related
Review for gene: PTBP1 was set to GREEN
Added comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Variants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability.
Sources: Literature
Skeletal dysplasia v0.337 PTBP1 Lucy Spencer gene: PTBP1 was added
gene: PTBP1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP1 were set to 40965981
Phenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related
Review for gene: PTBP1 was set to GREEN
Added comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Variants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.350 PTBP1 Lucy Spencer gene: PTBP1 was added
gene: PTBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP1 were set to 40965981
Phenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related
Review for gene: PTBP1 was set to GREEN
Added comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Variants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability.
Sources: Literature
Mendeliome v1.3362 PTBP1 Lucy Spencer changed review comment from: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss
variants also leading to increased protein stability.; to: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%).

Variants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.

Various functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss
variants also leading to increased protein stability.
Mendeliome v1.3362 PTBP1 Lucy Spencer reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40965981; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), PTBP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.350 PTBP2 Lucy Spencer gene: PTBP2 was added
gene: PTBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP2 were set to 40965981
Phenotypes for gene: PTBP2 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP2-related
Review for gene: PTBP2 was set to AMBER
Added comment: PMID: 40965981 2 males with developmental delay, ID, autistic features. 1 had some dysmorphic features and tonic-clonic seizures. both probands had a de novo variant in PTBP2 NM_021190.4:c.2T>C (p.Met1?) and NM_021190.4:c.41G>C (p.Arg14Thr), absent from gnomad. Transfection of the variants in transfection in NIH-3T3 cells showed the missense had cytoplasmic retention and colocalization with processing bodies, and that there were 2 alternative downstream start sites Met32 and Met35 that may be used instead.
Sources: Literature
Mendeliome v1.3362 PTBP2 Lucy Spencer gene: PTBP2 was added
gene: PTBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP2 were set to 40965981
Phenotypes for gene: PTBP2 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP2-related
Review for gene: PTBP2 was set to AMBER
Added comment: PMID: 40965981 2 males with developmental delay, ID, autistic features. 1 had some dysmorphic features and tonic-clonic seizures. both probands had a de novo variant in PTBP2 NM_021190.4:c.2T>C (p.Met1?) and NM_021190.4:c.41G>C (p.Arg14Thr), absent from gnomad. Transfection of the variants in transfection in NIH-3T3 cells showed the missense had cytoplasmic retention and colocalization with processing bodies, and that there were 2 alternative downstream start sites Met32 and Met35 that may be used instead.
Sources: Literature
Mendeliome v1.3362 GSTZ1 Lucy Spencer changed review comment from: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron.
Sources: Literature; to: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron. Val99Met has 1170 hets and 4 homs in gnomad, as this condition appears to be clinically benign this is not a concern.

Currently rated as moderate by ClinGen, the review does not include the most recent paper
Sources: Literature
Aminoacidopathy v1.135 GSTZ1 Lucy Spencer reviewed gene: GSTZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27876694, 38535121, 41009955; Phenotypes: Maleylacetoacetate isomerase deficiency MIM#617596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3362 GSTZ1 Lucy Spencer gene: GSTZ1 was added
gene: GSTZ1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSTZ1 were set to 27876694; 38535121; 41009955
Phenotypes for gene: GSTZ1 were set to Maleylacetoacetate isomerase deficiency MIM#617596
Review for gene: GSTZ1 was set to GREEN
Added comment: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1 compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.

PMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.

PMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A variant showed it lead to the out of frame 10bp retention of the intron.
Sources: Literature
Fetal anomalies v1.438 ITGAV Zornitza Stark Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Fetal anomalies v1.437 ITGAV Zornitza Stark Classified gene: ITGAV as Green List (high evidence)
Fetal anomalies v1.437 ITGAV Zornitza Stark Gene: itgav has been classified as Green List (High Evidence).
Fetal anomalies v1.436 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Intellectual disability syndromic and non-syndromic v1.350 ITGAV Zornitza Stark Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Intellectual disability syndromic and non-syndromic v1.349 ITGAV Zornitza Stark Classified gene: ITGAV as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.349 ITGAV Zornitza Stark Gene: itgav has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.348 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Disorders of immune dysregulation v1.30 ITGAV Zornitza Stark Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Disorders of immune dysregulation v1.29 ITGAV Zornitza Stark Classified gene: ITGAV as Green List (high evidence)
Disorders of immune dysregulation v1.29 ITGAV Zornitza Stark Gene: itgav has been classified as Green List (High Evidence).
Disorders of immune dysregulation v1.28 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Mendeliome v1.3362 ITGAV Zornitza Stark Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Mendeliome v1.3361 ITGAV Zornitza Stark Classified gene: ITGAV as Green List (high evidence)
Mendeliome v1.3361 ITGAV Zornitza Stark Gene: itgav has been classified as Green List (High Evidence).
Mendeliome v1.3360 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372
Mendeliome v1.3360 ITGAV Zornitza Stark edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Intellectual disability syndromic and non-syndromic v1.348 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Intellectual disability syndromic and non-syndromic v1.347 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Genetic Epilepsy v1.241 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Genetic Epilepsy v1.240 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Mendeliome v1.3360 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Mendeliome v1.3359 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Differences of Sex Development v1.22 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Differences of Sex Development v1.21 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Autism v0.222 UBR5 Zornitza Stark Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372
Autism v0.221 UBR5 Zornitza Stark reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None
Mendeliome v1.3359 CDK9 Bryony Thompson Classified gene: CDK9 as Green List (high evidence)
Mendeliome v1.3359 CDK9 Bryony Thompson Gene: cdk9 has been classified as Green List (High Evidence).
Mendeliome v1.3358 CDK9 Bryony Thompson gene: CDK9 was added
gene: CDK9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK9 were set to 40954203; 33640901; 30237576; 26633546
Phenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy
Review for gene: CDK9 was set to GREEN
Added comment: Biallelic variants in at least six unrelated families:
1) proband that displays retinal dystrophy without a CHARGE-like malformation syndrome (c.862G>A/p.A288T + c.961C>T/p.P321S).
2) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C),
3-7) 4 consanguineous families homozygous for p.R225C, including a set of cousins.
CDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy
Sources: Literature
Early-onset Dementia v1.48 DNMT1 Chirag Patel Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Mendeliome v1.3357 DNMT1 Chirag Patel Source Victorian Clinical Genetics Services was removed from DNMT1.
Source ClinGen was added to DNMT1.
Source Literature was added to DNMT1.
Phenotypes for gene: DNMT1 were changed from Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116 to Hereditary sensory neuropathy-deafness-dementia syndrome, MONDO:0013584
Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Deafness_IsolatedAndComplex v1.232 DNMT1 Chirag Patel Source Melbourne Genomics Health Alliance Deafness Flagship was removed from DNMT1.
Source Victorian Clinical Genetics Services was removed from DNMT1.
Source ClinGen was added to DNMT1.
Source Literature was added to DNMT1.
Phenotypes for gene: DNMT1 were changed from Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116 to Hereditary sensory neuropathy-deafness-dementia syndrome, MONDO:0013584
Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Hereditary Neuropathy_CMT - isolated v1.66 DNMT1 Chirag Patel Source Royal Melbourne Hospital was removed from DNMT1.
Source ClinGen was added to DNMT1.
Source Literature was added to DNMT1.
Phenotypes for gene: DNMT1 were changed from Neuropathy, hereditary sensory, type IE, 614116; Dementia, Deafness, and Sensory Neuropathy; HSAN/SFN to Hereditary sensory neuropathy-deafness-dementia syndrome, MONDO:0013584
Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Early-onset Dementia v1.47 DNMT1 Chirag Patel Source Melbourne Genomics Health Alliance Complex Neurology Flagship was removed from DNMT1.
Source Victorian Clinical Genetics Services was removed from DNMT1.
Source ClinGen was added to DNMT1.
Mode of inheritance for gene DNMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DNMT1 were changed from to Hereditary sensory neuropathy-deafness-dementia syndrome, MONDO:0013584
Publications for gene DNMT1 were changed from 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457 to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457
Mendeliome v1.3356 DNM1L Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1L.
Source Literature was added to DNM1L.
Source ClinGen was added to DNM1L.
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR); Optic atrophy 5 - MIM#610708 (AD) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726; Optic atrophy 5 - MIM#610708 (AD)
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748, 28969390, 30850373, 17460227 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748, 28969390, 30850373, 17460227
Intellectual disability syndromic and non-syndromic v1.347 DNM1L Chirag Patel Source Genetic Health Queensland was removed from DNM1L.
Source ClinGen was added to DNM1L.
Source Literature was added to DNM1L.
Mode of pathogenicity for gene DNM1L was changed from to Other
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388 to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748
Mitochondrial disease v0.1082 DNM1L Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1L.
Source Australian Genomics Health Alliance Mitochondrial Flagship was removed from DNM1L.
Source ClinGen was added to DNM1L.
Source Literature was added to DNM1L.
Mode of inheritance for gene DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity for gene DNM1L was changed from to Other
Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748
Peroxisomal Disorders v0.55 DNM1L Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1L.
Source Literature was added to DNM1L.
Source ClinGen was added to DNM1L.
Mode of inheritance for gene DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity for gene DNM1L was changed from to Other
Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748
Genetic Epilepsy v1.239 DNM1L Chirag Patel Source Victorian Clinical Genetics Services was removed from DNM1L.
Source Australian Genomics Health Alliance Epilepsy Flagship was removed from DNM1L.
Source ClinGen was added to DNM1L.
Source Literature was added to DNM1L.
Mode of pathogenicity for gene DNM1L was changed from to Other
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748
Fetal anomalies v1.436 DNM1L Chirag Patel Source Genomics England PanelApp was removed from DNM1L.
Source Genetic Health Queensland was removed from DNM1L.
Source ClinGen was added to DNM1L.
Source Literature was added to DNM1L.
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388 to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MONDO:0013726
Publications for gene DNM1L were changed from 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748 to 31587467, 27145208, 26604000, 27301544, 26931468, 33718295, 30109270, 26825290, 27328748
Mendeliome v1.3355 DES Chirag Patel Source Victorian Clinical Genetics Services was removed from DES.
Source ClinGen was added to DES.
Source Literature was added to DES.
Phenotypes for gene: DES were changed from Cardiomyopathy, dilated, 1I, MIM# 604765; Myopathy, myofibrillar, 1 , MIM#601419; Arrhythmogenic right ventricular cardiomyopathy to Cardiomyopathy, dilated, 1I, MIM# 604765; Myofibrillar myopathy 1, MONDO:0011076; Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Publications for gene DES were changed from 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203, 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792 to 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203, 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.63 DES Chirag Patel Phenotypes for gene: DES were changed from Myopathy, myofibrillar, 1 601419 to Myofibrillar myopathy 1, MONDO:0011076
Publications for gene DES were changed from 22395865, 20718792 to 22395865, 20718792
Arrhythmogenic Cardiomyopathy v0.73 DES Chirag Patel Publications for gene DES were changed from 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792 to 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 22395865, 20718792
Arrhythmogenic Cardiomyopathy v0.72 DES Chirag Patel Phenotypes for gene: DES were changed from Cardiomyopathy, dilated, 1I, MIM# 604765; Myopathy, myofibrillar, 1 , MIM#601419; Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Publications for gene DES were changed from 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 20718792 to 19879535, 20423733, 23168288, 20829228, 22403400, 29212896, 20718792
Dilated Cardiomyopathy v1.47 DES Chirag Patel Source Victorian Clinical Genetics Services was removed from DES.
Source ClinGen was added to DES.
Publications for gene DES were changed from 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203 to 10430757, 11728149, 17325244, 23300193, 31514951, 26724190, 23349452, 25557463, 19879535, 33947203
Proteinuria v0.231 DAAM2 Chirag Patel Publications for gene DAAM2 were changed from 33232676; 38860410 to 33232676; 38860410
Mendeliome v1.3354 DAAM2 Chirag Patel Publications for gene DAAM2 were changed from 33232676; 38860410; 36972684 to 33232676; 38860410; 36972684
Mendeliome v1.3353 FAP Sangavi Sivagnanasundram gene: FAP was added
gene: FAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FAP were set to 40949908
Phenotypes for gene: FAP were set to congenital pulmonary airway malformation MONDO:0016580
Review for gene: FAP was set to RED
Added comment: Only 1 reported fetus with a diagnosis of congenital pulmonary airway malformation
Heterozygous variant identified - c.T269G:p.L90W.
The variant is present in gnomAD v4.1 - EAS AF - 0.007% (4 hets)
Sources: Literature
Fetal anomalies v1.435 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.147 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v1.40 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v1.88 PDIA6 Sarah Milton reviewed gene: PDIA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 40974269, 35856135, 33495992; Phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.3353 PDIA6 Sarah Milton edited their review of gene: PDIA6: Changed phenotypes: multiple congenital anomalies, MONDO:0019042, PDIA6-related
Intellectual disability syndromic and non-syndromic v1.346 SF1 Sarah Milton changed review comment from: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing

PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15).
Variant types included missense and high impact LOF (nonsense and frameshift).

Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets.
pLI for SF1 is 1 with overall few LOF variants in gene.

Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance.
Sources: Literature; to: SF1 is involved in the first step of spliceosome complex assembly by recognizing the intron branchpoint consensus sequence at the 3′ splice site of the pre-mRNA. It is also involved in regulating alternative splicing

PMID: 40987292 describes 15 affected individuals with a neurodevelopmental disorder with monoallelic variants in SF1. Affected individuals had developmental delay, mild to moderate ID, behavioural disorders, seizures (3/15), brachydactyly (5/15), nail hypoplasia (5/15).
12 confirmed to have de novo variants including missense and high impact LOF (nonsense and frameshift).

Most variants were appropriately rare in gnomAD v4 however one reported variant had 9 hets.
pLI for SF1 is 1 with overall few LOF variants in gene.

Supportive functional studies reported in publication. SF1 deficient neural progenitor cells showed altered gene expression in genes involved in neuronal differentiation/synaptic transmission and axonal guidance.
Sources: Literature