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Mendeliome v1.1932 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Phenotypes for gene: HDAC3 were set to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6096 HDAC3 Zornitza Stark Phenotypes for gene: HDAC3 were changed from to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Genetic Epilepsy v1.34 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Phenotypes for gene: HDAC3 were set to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6093 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Marked gene: SLC39A14 as ready
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Gene: slc39a14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6091 SLC39A14 Zornitza Stark Publications for gene: SLC39A14 were set to
Intellectual disability syndromic and non-syndromic v0.6090 SLC39A14 Zornitza Stark Phenotypes for gene: SLC39A14 were changed from to Hypermanganesemia with dystonia 2 (MIM# 617013)
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Marked gene: TRPM3 as ready
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Classified gene: TRPM3 as Red List (low evidence)
Cerebral Palsy v1.365 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Red List (Low Evidence).
Mendeliome v1.1931 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111 to Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111; Combined immunodeficiency, MONDO:0015131, ITPR3-related
Mendeliome v1.1930 ITPR3 Zornitza Stark Publications for gene: ITPR3 were set to 32949214; 24627108
Mendeliome v1.1929 ITPR3 Zornitza Stark Mode of inheritance for gene: ITPR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1928 ITPR3 Zornitza Stark edited their review of gene: ITPR3: Changed publications: 32949214, 24627108, 36302985; Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111, Combined immunodeficiency, MONDO:0015131, ITPR3-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6089 COQ8A Ken Lee Wan reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31621627, 31741144; Phenotypes: coenzyme Q10 deficiency MONDO:0018151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Combined Immunodeficiency v1.69 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Combined immunodeficiency, MONDO:0015131, ITPR3-related to Combined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Marked gene: ITPR3 as ready
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from ombined immunodeficiency, MONDO:0015131, ITPR3-related to Combined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.68 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Combined Immune deficiency, immune dysregulation to ombined immunodeficiency, MONDO:0015131, ITPR3-related
Combined Immunodeficiency v1.67 ITPR3 Zornitza Stark Classified gene: ITPR3 as Green List (high evidence)
Combined Immunodeficiency v1.67 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.66 ITPR3 Zornitza Stark reviewed gene: ITPR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined immunodeficiency, MONDO:0015131, ITPR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496 to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6088 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6087 COL4A2 Zornitza Stark Publications for gene: COL4A2 were set to
Intellectual disability syndromic and non-syndromic v0.6086 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 34656997
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Intellectual disability syndromic and non-syndromic v0.6082 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1928 UNC93B1 Zornitza Stark Phenotypes for gene: UNC93B1 were changed from Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1 to Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, MIM#610551; Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Mendeliome v1.1927 UNC93B1 Zornitza Stark Publications for gene: UNC93B1 were set to 16973841; 29768176
Mendeliome v1.1926 UNC93B1 Zornitza Stark Mode of inheritance for gene: UNC93B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1925 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Green List (high evidence)
Mendeliome v1.1925 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Mendeliome v1.1924 UNC93B1 Zornitza Stark edited their review of gene: UNC93B1: Changed phenotypes: Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, MIM#610551, Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Mendeliome v1.1924 UNC93B1 Zornitza Stark edited their review of gene: UNC93B1: Added comment: PMID 38869500: Rare missense substitutions in UNC93B1 in probands from five unrelated kindreds presenting with early onset SLE (two probands) or CBL (three probands). Clinical, genetic, and functional in vitro and ex vivo data demonstrating changes in TLR7/8 signalling and trafficking.; Changed rating: GREEN; Changed publications: 29768176, 38869500; Changed phenotypes: Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1, Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Marked gene: UNC93B1 as ready
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.194 UNC93B1 Zornitza Stark Phenotypes for gene: UNC93B1 were changed from SLE, chilblain lupus to Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related
Disorders of immune dysregulation v0.193 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Green List (high evidence)
Disorders of immune dysregulation v0.193 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.192 UNC93B1 Zornitza Stark reviewed gene: UNC93B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, UNC93B1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6081 COQ4 Ken Lee Wan reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34656997; Phenotypes: mitochondrial disease MONDO:0044970, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1924 CD274 Zornitza Stark gene: CD274 was added
gene: CD274 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CD274 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD274 were set to 38634869
Phenotypes for gene: CD274 were set to Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790
Review for gene: CD274 was set to AMBER
Added comment: Two siblings, born to second-degree consanguineous parents of Moroccan descent, both developed neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk, respectively). One sibling was subsequently diagnosed with asthma at the age of 5 mo, auto-immune hypothyroidism at the age of 3 years, and growth hormone (GH) deficiency at the age of 10 years. He also had mild intellectual disability with delayed language development. By contrast, his sister had no clinical manifestations other than T1D.

Homozygous for splicing variant. This is the ligand of PD1, deficiency of which is also linked to immune dysregulation. Functional data.
Sources: Literature
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Marked gene: RNASEL as ready
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Gene: rnasel has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Marked gene: CD274 as ready
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.192 CD274 Zornitza Stark Phenotypes for gene: CD274 were changed from Immune dysregulation to Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790
Disorders of immune dysregulation v0.191 CD274 Zornitza Stark Classified gene: CD274 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.191 CD274 Zornitza Stark Gene: cd274 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.190 CD274 Zornitza Stark reviewed gene: CD274: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immune dysregulation, autoimmunity and auto inflammation, MONDO:0957790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Marked gene: SH2B3 as ready
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.190 SH2B3 Zornitza Stark Phenotypes for gene: SH2B3 were changed from Immune to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Disorders of immune dysregulation v0.189 SH2B3 Zornitza Stark Classified gene: SH2B3 as Green List (high evidence)
Disorders of immune dysregulation v0.189 SH2B3 Zornitza Stark Gene: sh2b3 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.188 SH2B3 Zornitza Stark reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Predisposition to haematological malignancies, Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Marked gene: NBEAL2 as ready
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.188 NBEAL2 Zornitza Stark Phenotypes for gene: NBEAL2 were changed from Immune dysregulation to Gray platelet syndrome, MIM# 139090; Immune dysregulation
Intellectual disability syndromic and non-syndromic v0.6081 COL4A2 Ken Lee Wan reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36324412, 39016117; Phenotypes: familial porencephaly MONDO:0020496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Disorders of immune dysregulation v0.187 NBEAL2 Zornitza Stark Classified gene: NBEAL2 as Green List (high evidence)
Disorders of immune dysregulation v0.187 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.186 NBEAL2 Zornitza Stark reviewed gene: NBEAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Gray platelet syndrome, MIM# 139090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.126 RNASEL Zornitza Stark Phenotypes for gene: RNASEL were changed from MIS-C to Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related
Susceptibility to Viral Infections v0.125 RNASEL Zornitza Stark Classified gene: RNASEL as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.125 RNASEL Zornitza Stark Gene: rnasel has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.124 RNASEL Zornitza Stark reviewed gene: RNASEL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Multisystem inflammatory syndrome, MONDO:0035375, RNASEL-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1923 OAS2 Zornitza Stark Marked gene: OAS2 as ready
Mendeliome v1.1923 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Mendeliome v1.1923 OAS2 Zornitza Stark Classified gene: OAS2 as Green List (high evidence)
Mendeliome v1.1923 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Mendeliome v1.1922 OAS2 Zornitza Stark gene: OAS2 was added
gene: OAS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS2 were set to 36538032
Phenotypes for gene: OAS2 were set to Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related
Review for gene: OAS2 was set to GREEN
Added comment: 3x unrelated patients with MIS-C after COVID infection. Patients displayed excessive inflammatory responses to intracellular dsRNA, SARS-CoV-2, SARS-CoV-2–infected cells, and their RNA, providing a plausible mechanism for MIS-C. Similar presentation to OAS1 and RNASEL. Functional data.
Sources: Literature
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Marked gene: OAS2 as ready
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.124 OAS2 Zornitza Stark Phenotypes for gene: OAS2 were changed from MIS-C to Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related
Susceptibility to Viral Infections v0.123 OAS2 Zornitza Stark Classified gene: OAS2 as Green List (high evidence)
Susceptibility to Viral Infections v0.123 OAS2 Zornitza Stark Gene: oas2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.122 OAS2 Zornitza Stark reviewed gene: OAS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36538032; Phenotypes: Multisystem inflammatory syndrome, MONDO:0035375, OAS2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1921 NFATC2 Zornitza Stark Phenotypes for gene: NFATC2 were changed from Skeletal system disorder MONDO:0005172 to Skeletal system disorder MONDO:0005172; Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Mendeliome v1.1920 NFATC2 Zornitza Stark Publications for gene: NFATC2 were set to 35789258
Mendeliome v1.1919 NFATC2 Zornitza Stark reviewed gene: NFATC2: Rating: RED; Mode of pathogenicity: None; Publications: 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.122 NFATC2 Zornitza Stark Phenotypes for gene: NFATC2 were changed from EBV associated lymphoproliferative disease to Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Susceptibility to Viral Infections v0.121 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Susceptibility to Viral Infections v0.121 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.120 NFATC2 Zornitza Stark reviewed gene: NFATC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Marked gene: CLN8 as ready
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Gene: cln8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Phenotypes for gene: CLN8 were changed from to neuronal ceroid lipofuscinosis MONDO:0016295
Intellectual disability syndromic and non-syndromic v0.6080 CLN8 Zornitza Stark Mode of inheritance for gene: CLN8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6079 CLN8 Ken Lee Wan reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neuronal ceroid lipofuscinosis MONDO:0016295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Marked gene: IKBKE as ready
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1919 IKBKE Zornitza Stark Marked gene: IKBKE as ready
Mendeliome v1.1919 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1919 IKBKE Zornitza Stark Classified gene: IKBKE as Amber List (moderate evidence)
Mendeliome v1.1919 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1918 IKBKE Zornitza Stark gene: IKBKE was added
gene: IKBKE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IKBKE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKBKE were set to 37937644
Phenotypes for gene: IKBKE were set to Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related
Review for gene: IKBKE was set to AMBER
Added comment: Single patient with recurrent HSV meningitis with supportive functional data.
Sources: Literature
Susceptibility to Viral Infections v0.120 IKBKE Zornitza Stark Phenotypes for gene: IKBKE were changed from Recurrent HSV encephalitis to Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related
Susceptibility to Viral Infections v0.119 IKBKE Zornitza Stark Classified gene: IKBKE as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.119 IKBKE Zornitza Stark Gene: ikbke has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.118 IKBKE Zornitza Stark reviewed gene: IKBKE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalitis, acute, infection-induced, susceptibility to, MONDO:0800174, IKBKE-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1917 SYCP2L Zornitza Stark Publications for gene: SYCP2L were set to 32303603
Mendeliome v1.1916 SYCP2L Zornitza Stark Classified gene: SYCP2L as Green List (high evidence)
Mendeliome v1.1916 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Green List (High Evidence).
Mendeliome v1.1915 SYCP2L Zornitza Stark changed review comment from: PMID: 38521400 - A homozygous nonsense variant segregated with POI in a pedigree with two affected sisters (c.1528C>T, p.(Gln510Ter)) PMID: 32303603 - Two unrelated individuals with premature ovarian insufficiency and homozygous variants (c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L. Concordant mouse model.; to: PMID: 38521400 - A homozygous nonsense variant segregated with POI in a pedigree with two affected sisters c.1528C>T, p.(Gln510Ter)
Mendeliome v1.1915 SYCP2L Zornitza Stark reviewed gene: SYCP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 38521400; Phenotypes: Premature ovarian failure 24, MIM# 620840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.330 SYCP2L Zornitza Stark Publications for gene: SYCP2L were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.329 SYCP2L Zornitza Stark Classified gene: SYCP2L as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.329 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.211 HBS1L Zornitza Stark Marked gene: HBS1L as ready
Syndromic Retinopathy v0.211 HBS1L Zornitza Stark Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Marked gene: LEO1 as ready
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Classified gene: LEO1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6078 LEO1 Zornitza Stark gene: LEO1 was added
gene: LEO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LEO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEO1 were set to 38965372
Phenotypes for gene: LEO1 were set to neurodevelopmental disorder MONDO:0700092, LEO-1 related
Review for gene: LEO1 was set to AMBER
Added comment: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
3 of the missense are said to lie within a region of missense constraint, however this isn't the case in v4
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6077 CHD2 Zornitza Stark Phenotypes for gene: CHD2 were changed from Epileptic encephalopathy, childhood-onset (MIM # 615369) to Developmental and epileptic encephalopathy 94, MIM# 615369
Intellectual disability syndromic and non-syndromic v0.6076 CHD2 Zornitza Stark Publications for gene: CHD2 were set to
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Zornitza Stark reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 94, MIM# 615369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Ken Lee Wan reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26677509; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Susceptibility to Viral Infections v0.118 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.118 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.117 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901
Mendeliome v1.1915 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs to Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901; isolated susceptibility to cutaneous α- and γ-HPVs
Mendeliome v1.1914 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#620901, isolated susceptibility to cutaneous α- and γ-HPVs
Mendeliome v1.1914 CD28 Zornitza Stark edited their review of gene: CD28: Changed phenotypes: Immunodeficiency-123 with HPV-related verrucosis (IMD123), MIM#62090, isolated susceptibility to cutaneous α- and γ-HPVs
Renal Macrocystic Disease v0.70 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Polycystic kidney disease 8, MIM# 620903
Renal Macrocystic Disease v0.69 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 8, MIM# 620903; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1914 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Polycystic kidney disease 8, MIM# 620903
Mendeliome v1.1913 NEK8 Zornitza Stark edited their review of gene: NEK8: Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Polycystic kidney disease 8, MIM# 620903
Ciliopathies v1.55 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Polycystic kidney disease 8, MIM# 620903
Ciliopathies v1.54 NEK8 Zornitza Stark edited their review of gene: NEK8: Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Polycystic kidney disease 8, MIM# 620903
Intellectual disability syndromic and non-syndromic v0.6075 RBBP5 Ain Roesley Phenotypes for gene: RBBP5 were changed from to neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 RBBP5 Ain Roesley edited their review of gene: RBBP5: Changed phenotypes: neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Marked gene: PCBP2 as ready
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1913 LEO1 Ain Roesley changed review comment from: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
3 of the missense are said to lie within a region of missense constraint, however this isn't the case in v4

Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Classified gene: PCBP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6073 PCBP2 Ain Roesley gene: PCBP2 was added
gene: PCBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCBP2 were set to 38965372
Phenotypes for gene: PCBP2 were set to neurodevelopmental disorder MONDO:0700092, PCBP2-related
Review for gene: PCBP2 was set to GREEN
gene: PCBP2 was marked as current diagnostic
Added comment: 3x individuals with de novo variants
Motor and speech delay and ASD
2x missense + 1x fs

There are 2 NMD variants with 9 and 8 hets respectively in gnomad v4, however the IGV looks to be low quality
Sources: Literature
Mendeliome v1.1913 PCBP2 Ain Roesley Marked gene: PCBP2 as ready
Mendeliome v1.1913 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1913 PCBP2 Ain Roesley Classified gene: PCBP2 as Green List (high evidence)
Mendeliome v1.1913 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Mendeliome v1.1912 PCBP2 Ain Roesley gene: PCBP2 was added
gene: PCBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCBP2 were set to 38965372
Phenotypes for gene: PCBP2 were set to neurodevelopmental disorder MONDO:0700092, PCBP2-related
Review for gene: PCBP2 was set to GREEN
gene: PCBP2 was marked as current diagnostic
Added comment: 3x individuals with de novo variants
Motor and speech delay and ASD
2x missense + 1x fs

There are 2 NMD variants with 9 and 8 hets respectively in gnomad v4, however the IGV looks to be low quality
Sources: Literature
Prepair 1000+ v1.76 ADAT3 Cassandra Muller changed review comment from: 20+ unrelated Arab families reported in the literature with the same homozygous missense variant in this gene causing intellectual disability (p.(Val128Met))
Other features can include microcephaly, growth failure, epilepsy.; to: 20+ unrelated Arab families reported in the literature with the same homozygous missense variant in this gene causing intellectual disability (p.(Val128Met)). One known family with a different variant in the same gene.
Other features can include microcephaly, growth failure, epilepsy.
Prepair 1000+ v1.76 ADAT3 Cassandra Muller reviewed gene: ADAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23620220, 26842963, 29796286, 30296593, 35118659; Phenotypes: Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM#615286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1911 LEO1 Ain Roesley changed review comment from: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Mendeliome v1.1911 LEO1 Ain Roesley changed review comment from: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature; to: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Prepair 1000+ v1.76 ERCC6L2 Lucy Spencer reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37696499, 29987015; Phenotypes: Bone marrow failure syndrome 2 MIM#615715; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1911 LEO1 Ain Roesley Marked gene: LEO1 as ready
Mendeliome v1.1911 LEO1 Ain Roesley Gene: leo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1911 LEO1 Ain Roesley Classified gene: LEO1 as Amber List (moderate evidence)
Mendeliome v1.1911 LEO1 Ain Roesley Gene: leo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1910 LEO1 Ain Roesley gene: LEO1 was added
gene: LEO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEO1 were set to 38965372
Phenotypes for gene: LEO1 were set to neurodevelopmental disorder MONDO:0700092, LEO-1 related
Review for gene: LEO1 was set to AMBER
gene: LEO1 was marked as current diagnostic
Added comment: enrichment of a neurodev cohort
LEO1:
8x de novo – 6x missense + 2x PTC
1x pat splice
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
Sources: Literature
Prepair 1000+ v1.76 DYNC1I2 Lucy Spencer reviewed gene: DYNC1I2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31079899; Phenotypes: Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 ACADM Cassandra Muller reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: 9158144; Phenotypes: Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM #201450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 DHODH Lucy Spencer reviewed gene: DHODH: Rating: GREEN; Mode of pathogenicity: None; Publications: 19915526; Phenotypes: Miller syndrome, MIM# 263750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CTSC Lucy Spencer reviewed gene: CTSC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Haim-Munk syndrome MIM#245010, Papillon-Lefevre syndrome MIM#245000, Periodontitis 1, juvenile MIM#170650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CPT2 Lucy Spencer reviewed gene: CPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32295037; Phenotypes: CPT II deficiency, infantile MIM#600649, CPT II deficiency, lethal neonatal MIM#608836, CPT II deficiency, myopathic, stress-induced MIM#255110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 COX20 Lucy Spencer reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751098; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.76 CLN6 Lucy Spencer reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30561534; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.65 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Muscular dystrophy and myopathy_Paediatric v1.65 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.76 CERKL Lucy Spencer reviewed gene: CERKL: Rating: AMBER; Mode of pathogenicity: None; Publications: 37331655; Phenotypes: Retinitis pigmentosa 26 (MIM#608380); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.16 EMILIN1 Zornitza Stark edited their review of gene: EMILIN1: Added comment: PMID 38963291: additional variant reported in an individual with neuropathy; however limited supporting evidence.; Changed publications: 31978608, 26462740, 38963291
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Marked gene: KCNJ10 as ready
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Classified gene: KCNJ10 as Green List (high evidence)
Paroxysmal Dyskinesia v0.133 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Mendeliome v1.1909 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from SESAME syndrome, MIM# 612780 to SESAME syndrome, MIM# 612780; Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related
Mendeliome v1.1908 KCNJ10 Zornitza Stark Publications for gene: KCNJ10 were set to 19289823; 19420365; 21849804; 11466414
Mendeliome v1.1907 KCNJ10 Zornitza Stark Mode of inheritance for gene: KCNJ10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1906 KCNJ10 Zornitza Stark edited their review of gene: KCNJ10: Added comment: PMID 38979912: 11 individuals from 8 unrelated families reported with variants in this gene and paroxysmal dyskinesia. Notably one was the parent of a child with recessive SeSAME syndrome (established gene-disease association). Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.; Changed publications: 19289823, 19420365, 21849804, 11466414, 38979912; Changed phenotypes: SESAME syndrome, MIM# 612780, Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paroxysmal Dyskinesia v0.132 KCNJ10 Zornitza Stark gene: KCNJ10 was added
gene: KCNJ10 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: KCNJ10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ10 were set to 38979912
Phenotypes for gene: KCNJ10 were set to Paroxysmal dyskinesia, MONDO:0015427, KCNJ10-related
Review for gene: KCNJ10 was set to GREEN
Added comment: 11 individuals from 8 unrelated families reported with variants in this gene and paroxysmal dyskinesia. Notably one was the parent of a child with recessive SeSAME syndrome (established gene-disease association). Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.
Sources: Literature
Mendeliome v1.1906 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to 28434495
Mendeliome v1.1905 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Green List (high evidence)
Mendeliome v1.1905 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Green List (High Evidence).
Mendeliome v1.1904 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Added comment: PMID 39003656: additional individual with compound het missense variants and supportive functional data.; Changed rating: GREEN; Changed publications: 28434495, 39003656
Intellectual disability syndromic and non-syndromic v0.6072 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to 28434495
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6070 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Added comment: PMID 39003656: additional individual with compound het missense variants and supportive functional data.; Changed rating: GREEN; Changed publications: 28434495, 39003656
Callosome v0.525 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495; 39073169
Callosome v0.524 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed publications: 39073169
Syndromic Retinopathy v0.211 HBS1L Bryony Thompson Classified gene: HBS1L as Amber List (moderate evidence)
Syndromic Retinopathy v0.211 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6070 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495; 39073169
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed publications: 39073169
Fetal anomalies v1.257 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.257 SRPK3 Zornitza Stark Classified gene: SRPK3 as Amber List (moderate evidence)
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.210 HBS1L Bryony Thompson gene: HBS1L was added
gene: HBS1L was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: HBS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBS1L were set to 38966981; 24288412; 30707697
Phenotypes for gene: HBS1L were set to Retinal disorder MONDO:0005283
Review for gene: HBS1L was set to AMBER
Added comment: A single case with biallelic variants reported with retinal dystrophy, poor growth and neurodevelopmental delay (originally reported in 2013). A hypomorph mouse model demonstrated defective development of photoreceptor cells.
Sources: Literature
Fetal anomalies v1.256 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to AMBER
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Callosome v0.524 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Callosome v0.524 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Callosome v0.524 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Callosome v0.524 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Callosome v0.523 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495; 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to GREEN
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1904 HBS1L Bryony Thompson Marked gene: HBS1L as ready
Mendeliome v1.1904 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6068 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495; 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to GREEN
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Mendeliome v1.1904 HBS1L Bryony Thompson Classified gene: HBS1L as Amber List (moderate evidence)
Mendeliome v1.1904 HBS1L Bryony Thompson Gene: hbs1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1903 HBS1L Bryony Thompson gene: HBS1L was added
gene: HBS1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HBS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HBS1L were set to 38966981; 24288412; 30707697
Phenotypes for gene: HBS1L were set to Retinal disorder MONDO:0005283
Review for gene: HBS1L was set to AMBER
Added comment: A single case with biallelic variants reported with retinal dystrophy, poor growth and neurodevelopmental delay (originally reported in 2013). A hypomorph mouse model demonstrated defective development of photoreceptor cells.
Sources: Literature
Mendeliome v1.1902 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related; Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Mendeliome v1.1901 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Marked STR: OPDM4_RILPL1_CGG as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Str: opdm4_rilpl1_cgg has been classified as Green List (High Evidence).
Mendeliome v1.1900 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related, Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Mendeliome v1.1900 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).; Changed publications: 38429495, 39073169
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Classified STR: OPDM4_RILPL1_CGG as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 OPDM4_RILPL1_CGG Bryony Thompson Str: opdm4_rilpl1_cgg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.36 OPDM4_RILPL1_CGG Bryony Thompson STR: OPDM4_RILPL1_CGG was added
STR: OPDM4_RILPL1_CGG was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM4_RILPL1_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4_RILPL1_CGG were set to 35148830
Phenotypes for STR: OPDM4_RILPL1_CGG were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4_RILPL1_CGG was set to GREEN
STR: OPDM4_RILPL1_CGG was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion.
Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.35 Bryony Thompson removed STR:OPDM1_LRP12_CGG from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.34 OPDM1_LRP12_CGG Bryony Thompson Classified STR: OPDM1_LRP12_CGG as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.34 OPDM1_LRP12_CGG Bryony Thompson Str: opdm1_lrp12_cgg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.33 OPDM1_LRP12_CGG Bryony Thompson STR: OPDM1_LRP12_CGG was added
STR: OPDM1_LRP12_CGG was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM1_LRP12_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM1_LRP12_CGG were set to 31332380; 34047774
Phenotypes for STR: OPDM1_LRP12_CGG were set to oculopharyngodistal myopathy 1 MONDO:0020793
Review for STR: OPDM1_LRP12_CGG was set to GREEN
STR: OPDM1_LRP12_CGG was marked as clinically relevant
Added comment: NM_013437.5:c.-102CGG[X]
RNA-mediated toxicity is thought to be the mechanism of disease. Sixty-five Japanese patients with oculopharyngodistal myopathy (OPDM) from 59 families with CGG repeat expansions in LRP12. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM.
Normal: 13 to 45 repeats.
Pathogenic: 85 to 289 repeats.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Marked gene: RBBP5 as ready
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Mendeliome v1.1900 RBBP5 Ain Roesley Marked gene: RBBP5 as ready
Mendeliome v1.1900 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6066 RBBP5 Ain Roesley gene: RBBP5 was added
gene: RBBP5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBBP5 were set to 39036895
Review for gene: RBBP5 was set to GREEN
gene: RBBP5 was marked as current diagnostic
Added comment: 5x Indivs (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (<= -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.32 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.31 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to 39068203
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Literature
Mendeliome v1.1900 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Mendeliome v1.1900 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1900 RBBP5 Ain Roesley changed review comment from: 5x Indivis (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia; to: 5x Indivs (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Mendeliome v1.1900 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Mendeliome v1.1900 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1899 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Mendeliome v1.1898 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Hereditary Neuropathy - complex v1.16 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Mendeliome v1.1897 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to 39068203
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Literature
Hereditary Neuropathy - complex v1.15 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6064 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Mendeliome v1.1896 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Mendeliome v1.1896 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Mendeliome v1.1895 RBBP5 Ain Roesley commented on gene: RBBP5: 5x Indivis (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (< -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Mendeliome v1.1895 RBBP5 Ain Roesley Deleted their comment
Mendeliome v1.1895 RBBP5 Ain Roesley gene: RBBP5 was added
gene: RBBP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBBP5 were set to 39036895
Phenotypes for gene: RBBP5 were set to neurodevelopmental disorder MONDO:0700092, RBBP5-related
Review for gene: RBBP5 was set to GREEN
gene: RBBP5 was marked as current diagnostic
Added comment: 5 individuals with de novo variants - 3x PTCs + 2x missense

2/5 short stature (> 3SD; 2x >=-2SD)
1/5 microcephaly (> 3SD; 3x >=-2SD)
4/5 dev delay/ID
2/5 SNHL
2/5 Seizures
3/5 hypotonia
Sources: Literature
Repeat Disorders v0.167 OPDM_ABCD3_GCC Bryony Thompson edited their review of STR: OPDM_ABCD3_GCC: Changed publications: 39068203
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Marked gene: DPAGT1 as ready
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Gene: dpagt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Classified gene: DPAGT1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.65 DPAGT1 Bryony Thompson Gene: dpagt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.64 DPAGT1 Bryony Thompson gene: DPAGT1 was added
gene: DPAGT1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: DPAGT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPAGT1 were set to 38982518; 38443029; 38124360; 29356258; 24759841
Phenotypes for gene: DPAGT1 were set to tubular aggregate myopathy MONDO:0008051
Review for gene: DPAGT1 was set to GREEN
gene: DPAGT1 was marked as current diagnostic
Added comment: 3 cases reported with congenital myopathy, and at least 2 case with CMS mimicking a congenital myopathy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Marked gene: ALG14 as ready
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Gene: alg14 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Classified gene: ALG14 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.63 ALG14 Bryony Thompson Gene: alg14 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.76 CLCNKB Lilian Downie Publications for gene: CLCNKB were set to
Muscular dystrophy and myopathy_Paediatric v1.62 ALG14 Bryony Thompson gene: ALG14 was added
gene: ALG14 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG14 were set to 38982518; 28733338
Phenotypes for gene: ALG14 were set to congenital myopathy MONDO:0019952
Review for gene: ALG14 was set to AMBER
gene: ALG14 was marked as current diagnostic
Added comment: 2 cases have been reported with congenital myopathy with biallelic variants.
Sources: Literature
Prepair 1000+ v1.75 CLCN4 Lilian Downie Marked gene: CLCN4 as ready
Prepair 1000+ v1.75 CLCN4 Lilian Downie Gene: clcn4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.75 CLCN4 Lilian Downie Publications for gene: CLCN4 were set to 27550844
Prepair 1000+ v1.74 CIITA Lilian Downie Marked gene: CIITA as ready
Prepair 1000+ v1.74 CIITA Lilian Downie Gene: ciita has been classified as Green List (High Evidence).
Prepair 1000+ v1.74 CIITA Lilian Downie Publications for gene: CIITA were set to
Prepair 1000+ v1.73 CEP290 Lilian Downie Marked gene: CEP290 as ready
Prepair 1000+ v1.73 CEP290 Lilian Downie Gene: cep290 has been classified as Green List (High Evidence).
Prepair 1000+ v1.73 CEP290 Lilian Downie Publications for gene: CEP290 were set to
Prepair 1000+ v1.72 CDT1 Lilian Downie Marked gene: CDT1 as ready
Prepair 1000+ v1.72 CDT1 Lilian Downie Gene: cdt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.72 CDT1 Lilian Downie Publications for gene: CDT1 were set to
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Marked gene: UNC45B as ready
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Classified gene: UNC45B as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.61 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Prepair 1000+ v1.71 CDK10 Lilian Downie Marked gene: CDK10 as ready
Prepair 1000+ v1.71 CDK10 Lilian Downie Gene: cdk10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.71 CDK10 Lilian Downie Publications for gene: CDK10 were set to
Muscular dystrophy and myopathy_Paediatric v1.59 UNC45B Bryony Thompson gene: UNC45B was added
gene: UNC45B was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.70 CD55 Lilian Downie Marked gene: CD55 as ready
Prepair 1000+ v1.70 CD55 Lilian Downie Gene: cd55 has been classified as Green List (High Evidence).
Prepair 1000+ v1.70 CD55 Lilian Downie Publications for gene: CD55 were set to
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Marked gene: CASQ1 as ready
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Gene: casq1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Classified gene: CASQ1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.58 CASQ1 Bryony Thompson Gene: casq1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.69 CARD11 Lilian Downie Marked gene: CARD11 as ready
Prepair 1000+ v1.69 CARD11 Lilian Downie Added comment: Comment when marking as ready: Dominant negative suggested as possible mechanism for AD disease PMID:28826773
Prepair 1000+ v1.69 CARD11 Lilian Downie Gene: card11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.69 CARD11 Lilian Downie Publications for gene: CARD11 were set to
Muscular dystrophy and myopathy_Paediatric v1.57 CASQ1 Bryony Thompson gene: CASQ1 was added
gene: CASQ1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASQ1 were set to 38982518
Phenotypes for gene: CASQ1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: CASQ1 was set to Other
Review for gene: CASQ1 was set to AMBER
gene: CASQ1 was marked as current diagnostic
Added comment: 2 cases have been reported with congenital myopathy. Gain of function is expected to be the mechanism of disease.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Marked gene: ORAI1 as ready
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Gene: orai1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Classified gene: ORAI1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.56 ORAI1 Bryony Thompson Gene: orai1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.55 ORAI1 Bryony Thompson gene: ORAI1 was added
gene: ORAI1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ORAI1 were set to 31448844; 38982518
Phenotypes for gene: ORAI1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: ORAI1 was set to Other
Review for gene: ORAI1 was set to GREEN
gene: ORAI1 was marked as current diagnostic
Added comment: >4 cases with congenital myopathy. Gain of function is the mechanism of disease.
Sources: Literature
Prepair 1000+ v1.68 C19orf12 Lilian Downie Marked gene: C19orf12 as ready
Prepair 1000+ v1.68 C19orf12 Lilian Downie Gene: c19orf12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.68 C19orf12 Lilian Downie Publications for gene: C19orf12 were set to
Prepair 1000+ v1.67 ATM Lilian Downie Marked gene: ATM as ready
Prepair 1000+ v1.67 ATM Lilian Downie Added comment: Comment when marking as ready: NB for reporting carrier mother may need additional breast cancer surveillance
Prepair 1000+ v1.67 ATM Lilian Downie Gene: atm has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Marked gene: STIM1 as ready
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Gene: stim1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.67 ATM Lilian Downie Publications for gene: ATM were set to 30137827
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Classified gene: STIM1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.54 STIM1 Bryony Thompson Gene: stim1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.53 STIM1 Bryony Thompson gene: STIM1 was added
gene: STIM1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STIM1 were set to 38982518; 31448844
Phenotypes for gene: STIM1 were set to tubular aggregate myopathy MONDO:0008051
Mode of pathogenicity for gene: STIM1 was set to Other
Review for gene: STIM1 was set to GREEN
gene: STIM1 was marked as current diagnostic
Added comment: >4 cases with congenital myopathy. Gain of function is the mechanism of disease.
Sources: Literature
Prepair 1000+ v1.66 ATM Lilian Downie Publications for gene: ATM were set to
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson Marked gene: OPA1 as ready
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson Gene: opa1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.52 OPA1 Bryony Thompson gene: OPA1 was added
gene: OPA1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: OPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPA1 were set to 38982518
Phenotypes for gene: OPA1 were set to congenital myopathy MONDO:0019952
Review for gene: OPA1 was set to RED
Added comment: A single case with centronuclear myopathy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson Marked gene: IDUA as ready
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson Gene: idua has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.51 IDUA Bryony Thompson gene: IDUA was added
gene: IDUA was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 38982518
Phenotypes for gene: IDUA were set to congenital myopathy MONDO:0019952
Review for gene: IDUA was set to RED
gene: IDUA was marked as current diagnostic
Added comment: A single case reported with core myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson Marked gene: FOXP3 as ready
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson Gene: foxp3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.50 FOXP3 Bryony Thompson gene: FOXP3 was added
gene: FOXP3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 38982518
Phenotypes for gene: FOXP3 were set to congenital myopathy MONDO:0019952
Review for gene: FOXP3 was set to RED
gene: FOXP3 was marked as current diagnostic
Added comment: Single case reported with centronuclear myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.49 EXOSC3 Bryony Thompson gene: EXOSC3 was added
gene: EXOSC3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC3 were set to 30025162; 38982518
Phenotypes for gene: EXOSC3 were set to congenital myopathy MONDO:0019952
Review for gene: EXOSC3 was set to RED
Added comment: A single case reported with congenital myopathy as a feature of the condition (also including PCH).
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Marked gene: CHRNA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.30 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson Marked gene: CHRND as ready
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson Gene: chrnd has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.48 CHRND Bryony Thompson gene: CHRND was added
gene: CHRND was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CHRND was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHRND were set to 38982518
Phenotypes for gene: CHRND were set to congenital myopathy MONDO:0019952
Review for gene: CHRND was set to RED
gene: CHRND was marked as current diagnostic
Added comment: Single case with congenital centronuclear myopathy reported
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.29 CHRNA1 Bryony Thompson gene: CHRNA1 was added
gene: CHRNA1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA1 were set to 36634413
Phenotypes for gene: CHRNA1 were set to myasthenic syndrome, congenital, 1B, fast-channel MONDO:0012156
Review for gene: CHRNA1 was set to GREEN
gene: CHRNA1 was marked as current diagnostic
Added comment: 13 patients from nine unrelated families with acetylcholine receptor deficiency harbouring the CHRNA1 variant NM_001039523.3:c.257G>A (p.Arg86His) in homozygosity or compound heterozygosity with a predominant pattern of distal upper limb weakness in adulthood, similar to distal myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Classified gene: CHRNA1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.47 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson Marked gene: CHRNA1 as ready
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson Gene: chrna1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.46 CHRNA1 Bryony Thompson gene: CHRNA1 was added
gene: CHRNA1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CHRNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CHRNA1 were set to 36634413; 38982518
Phenotypes for gene: CHRNA1 were set to Congenital myopathy MONDO:0019952
Review for gene: CHRNA1 was set to AMBER
Added comment: Congenital myopathy reported in at least 2 cases. One biallelic (loss of function) and one monoallelic (gain of function).
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Marked gene: TTN as ready
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Gene: ttn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Classified gene: TTN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.45 TTN Bryony Thompson Gene: ttn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.44 TTN Bryony Thompson gene: TTN was added
gene: TTN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
digenic tags were added to gene: TTN.
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 38429495; 38982518
Phenotypes for gene: TTN were set to TTN-related myopathy MONDO:0100175
Review for gene: TTN was set to GREEN
gene: TTN was marked as current diagnostic
Added comment: >4 cases reported with biallelic variants and congenital myopathy (e.g. centronuclear myopathy, cytoplasmic bodies). Digenic heterozygous TTN/SRPK3 variants are also reported with core myopathy.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Marked gene: MYH7 as ready
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Gene: myh7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.43 MYH7 Bryony Thompson Mode of pathogenicity for gene: MYH7 was changed from None to None
Muscular dystrophy and myopathy_Paediatric v1.42 MYH7 Bryony Thompson Classified gene: MYH7 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.42 MYH7 Bryony Thompson Gene: myh7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.41 MYH7 Bryony Thompson edited their review of gene: MYH7: Changed mode of pathogenicity: Other
Muscular dystrophy and myopathy_Paediatric v1.41 MYH7 Bryony Thompson gene: MYH7 was added
gene: MYH7 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH7 were set to 38982518; 15322983
Phenotypes for gene: MYH7 were set to MYH7-related skeletal myopathy MONDO:0008050
Review for gene: MYH7 was set to GREEN
gene: MYH7 was marked as current diagnostic
Added comment: Congenital myopathy reported in >4 cases/families (e.g. core myopathy). The mechanism for disease is dominant negative.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Marked gene: MTM1 as ready
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Gene: mtm1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Classified gene: MTM1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.40 MTM1 Bryony Thompson Gene: mtm1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.39 MTM1 Bryony Thompson gene: MTM1 was added
gene: MTM1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MTM1 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: MTM1 were set to 30232666; 38982518; 10790201
Phenotypes for gene: MTM1 were set to X-linked myotubular myopathy MONDO:0010683
Review for gene: MTM1 was set to GREEN
gene: MTM1 was marked as current diagnostic
Added comment: >4 cases reported with congenital myopathy (congenital fiber type disorder, centronuclear myopathy, myotubular myopathy). Hemizygous males and heterozygous females are reported.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Classified gene: FHL1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Gene: fhl1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.38 FHL1 Bryony Thompson Publications for gene: FHL1 were set to PMID: 19181672; 19171836
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Marked gene: CAV3 as ready
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Gene: cav3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Classified gene: CAV3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.37 CAV3 Bryony Thompson Gene: cav3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.36 CAV3 Bryony Thompson gene: CAV3 was added
gene: CAV3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAV3 were set to 38982518; 30174172
Phenotypes for gene: CAV3 were set to Caveolinopathy MONDO:0016146
Mode of pathogenicity for gene: CAV3 was set to Other
Review for gene: CAV3 was set to GREEN
gene: CAV3 was marked as current diagnostic
Added comment: At least 4 probands/families reported with congenital/paediatric onset myopathy (1 tubular aggregate myopathy and 3 rippling muscle disease). The mechanism for disease is expected to be dominant negative.
Sources: Literature
Prepair 1000+ v1.65 WNT1 Lauren Rogers reviewed gene: WNT1: Rating: ; Mode of pathogenicity: None; Publications: 23499310; Phenotypes: Osteogenesis imperfecta, type XV (MIM#615220); Mode of inheritance: None
Prepair 1000+ v1.65 WDR45B Lauren Rogers reviewed gene: WDR45B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28503735; Phenotypes: Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, MIM# 617977; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 VLDLR Lauren Rogers reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629, 10380922; Phenotypes: Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 USP9X Lauren Rogers reviewed gene: USP9X: Rating: ; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Intellectual developmental disorder, X-linked 99, MIM#300919; Mode of inheritance: None
Prepair 1000+ v1.65 TUFM Lauren Rogers changed review comment from: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset; to: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset
Prepair 1000+ v1.65 TUFM Lauren Rogers changed review comment from: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Co ngenital onset; to: Features are lactic acidosis, progressive encephalopathy, dysplastic leukoencephalopathy due to abberant mitochondrial DNA translation.

Congenital onset
Prepair 1000+ v1.65 TUFM Lauren Rogers reviewed gene: TUFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 4, OMIM #610678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 TUBGCP4 Lauren Rogers reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25817018; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 TPK1 Lauren Rogers reviewed gene: TPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458; Phenotypes: 33086386, 32679198, 22152682, 33231275; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 SYCP2L Elena Tucker reviewed gene: SYCP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38521400, PMID: 32303603; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SURF1 Lauren Rogers commented on gene: SURF1: Established gene-disease association.

Childhood onset, variable age, multi-system disorder characterised by rapidly progressive neurodegeneration and encephalopathy
Prepair 1000+ v1.65 SURF1 Lauren Rogers reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23829769; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SUCLG1 Lauren Rogers reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20693550; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SLC46A1 Lauren Rogers reviewed gene: SLC46A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301716; Phenotypes: Folate malabsorption, hereditary, MIM# 229050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 SGCG Lauren Rogers reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RNASEH2C Lauren Rogers reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 32877590; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RMRP Lauren Rogers edited their review of gene: RMRP: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RMRP Lauren Rogers reviewed gene: RMRP: Rating: ; Mode of pathogenicity: None; Publications: 16244706, 21396580, 22420014, 11940090, 16252239; Phenotypes: Cartilage-hair hypoplasia MIM#250250, Anauxetic dysplasia 1, MIM#607095, Metaphyseal dysplasia without hypotrichosis MIM#250460; Mode of inheritance: None
Prepair 1000+ v1.65 RIN2 Lauren Rogers reviewed gene: RIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631308, 20424861, 23963297, 24449201; Phenotypes: Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 RAB3GAP1 Lauren Rogers reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15696165, 20512159, 23420520, 30730599; Phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PMM2 Lauren Rogers edited their review of gene: PMM2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PMM2 Lauren Rogers reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065); Mode of inheritance: None
Prepair 1000+ v1.65 PLPBP Lauren Rogers reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30668673, 31741821; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM#617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PIGA Lauren Rogers reviewed gene: PIGA: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis, MIM#301072; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.65 PGM3 Lauren Rogers reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31231132, 33098103; Phenotypes: Immunodeficiency 23, MIM# 615816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 PGM1 Lauren Rogers reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24499211, 33342467; Phenotypes: Congenital disorder of glycosylation, type It (MIM#614921); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ORC1 Lauren Rogers reviewed gene: ORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358633, 21358632, 21358631, 23023959; Phenotypes: Meier-Gorlin syndrome 1, MIM# 224690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CLDN1 Andrew Coventry reviewed gene: CLDN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11889141 12164927 35304779 36779798; Phenotypes: Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis MIM#607626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 OBSL1 Lauren Rogers reviewed gene: OBSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058, 19481195, 23018678, 19877176; Phenotypes: 3-M syndrome 2 (MIM#612921); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 OBSL1 Lauren Rogers Deleted their review
Prepair 1000+ v1.65 OBSL1 Lauren Rogers reviewed gene: OBSL1: Rating: ; Mode of pathogenicity: None; Publications: 21737058, 19481195, 23018678, 19877176; Phenotypes: 3-M syndrome 2, MIM #612921; Mode of inheritance: None
Prepair 1000+ v1.65 NTNG2 Lauren Rogers reviewed gene: NTNG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31668703, 31692205; Phenotypes: Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 NKX3-2 Lauren Rogers reviewed gene: NKX3-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20004766, 29704686; Phenotypes: Spondylo-megaepiphyseal-metaphyseal dysplasia (MIM#613330); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CLCN4 Andrew Coventry reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27550844 33951195 25644381 34479510 37409888; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.65 CIITA Andrew Coventry reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893 9099848 11862382 28676232 24789686 20197681 11466404 15821736 12910265; Phenotypes: MHC class II deficiency 1 MIM#209920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CDK10 Andrew Coventry reviewed gene: CDK10: Rating: GREEN; Mode of pathogenicity: None; Publications: 28886341 29130579 34974531; Phenotypes: Al Kaissi syndrome MIM#617694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 NGLY1 Lauren Rogers reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24651605, 27388694; Phenotypes: Congenital disorder of deglycosylation, MIM# 615273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MOGS Lauren Rogers reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492, 38498292, 33261925; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 C19orf12 Andrew Coventry reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780 31087512 23269600 33688131 22508347 31804703 30088953 20039086 24586779 35182730; Phenotypes: Neurodegeneration with brain iron accumulation 4 MIM#614298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MOCS2 Lauren Rogers reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10053004, 31848698, 16021469, 30900395; Phenotypes: Molybdenum cofactor deficiency B (MIM#252160); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MMADHC Lauren Rogers reviewed gene: MMADHC: Rating: ; Mode of pathogenicity: None; Publications: 33552904; Phenotypes: Homocystinuria, cblD type, variant 1 MIM#277410, Methylmalonic aciduria and homocystinuria, cblD type MIM#277410, Methylmalonic aciduria, cblD type, variant 2 MIM#277410, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MEGF8 Lauren Rogers reviewed gene: MEGF8: Rating: ; Mode of pathogenicity: None; Publications: 23063620; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 MAN2B1 Lauren Rogers reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II, MIM# 248500, MONDO:0009561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 BCAP31 Andrew Coventry reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989 33603160 32681719; Phenotypes: Deafness, dystonia, and cerebral hypomyelination MIM#300475, Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.65 ISPD Lauren Rogers reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28688748, 30060766, 22522420; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM#614643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1894 BBS4 Andrew Coventry reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381270 12016587 10874630; Phenotypes: Bardet-Biedl syndrome 4 MIM#615982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.117 IKBKE Peter McNaughton gene: IKBKE was added
gene: IKBKE was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: IKBKE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKBKE were set to PMID: 37937644
Phenotypes for gene: IKBKE were set to Recurrent HSV encephalitis
Review for gene: IKBKE was set to AMBER
Added comment: Single patient with recurrent HSV meningitis with supportive functional data.
Sources: Literature
Prepair 1000+ v1.65 ABCC8 Andrew Coventry reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17919176 1950816 21716120 38791571 36034573; Phenotypes: Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857, Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.117 RNASEL Peter McNaughton gene: RNASEL was added
gene: RNASEL was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: RNASEL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEL were set to PMID: 36538032
Phenotypes for gene: RNASEL were set to MIS-C
Review for gene: RNASEL was set to AMBER
Added comment: Single patient presenting with similar presentation and functional findings to OAS1 and OAS2
Sources: Literature
Susceptibility to Viral Infections v0.117 OAS2 Peter McNaughton gene: OAS2 was added
gene: OAS2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: OAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAS2 were set to PMID: 36538032
Phenotypes for gene: OAS2 were set to MIS-C
Review for gene: OAS2 was set to GREEN
Added comment: 3x unrelated patients with MIS-C after COVID infection. Patients displayed excessive inflammatory responses to intracellular dsRNA, SARS-CoV-2, SARS-CoV-2–infected cells, and their RNA, providing a plausible mechanism for MIS-C. Similar presentation to OAS1 and RNASEL.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Classified gene: FBN1 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.73 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.72 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 31238364; 27138491; 17701892
Phenotypes for gene: FBN1 were set to Marfan syndrome, MIM# 154700; neonatal
Review for gene: FBN1 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Classified gene: FBLN5 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.71 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.70 FBLN5 Zornitza Stark gene: FBLN5 was added
gene: FBLN5 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FBLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBLN5 were set to Cutis laxa, autosomal recessive, type IA, MIM# 219100; childhood-onset emphysema
Review for gene: FBLN5 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Marked gene: FAT4 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Classified gene: FAT4 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.69 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.68 FAT4 Zornitza Stark gene: FAT4 was added
gene: FAT4 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: FAT4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT4 were set to 24913602; 14564208
Phenotypes for gene: FAT4 were set to Hennekam Syndrome, MIM# 235510; childhood pulmonary lymphangiectasia
Review for gene: FAT4 was set to GREEN
Added comment: Sources: Expert list
Prepair 1000+ v1.65 CLCNKB Lucy Spencer changed review comment from: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.; to: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.
Prepair 1000+ v1.65 CLCNKB Lucy Spencer reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25810436, 24965226; Phenotypes: Bartter syndrome, type 3 MIM#607364, Bartter syndrome, type 4b, digenic MIM#613090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v1.33 LDB3 Bryony Thompson reviewed gene: LDB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 14662268, 14660611, 35284542, 32041989; Phenotypes: dilated cardiomyopathy MONDO:0005021; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1894 LDB3 Bryony Thompson Deleted their comment
Mendeliome v1.1894 LDB3 Bryony Thompson Classified gene: LDB3 as Green List (high evidence)
Mendeliome v1.1894 LDB3 Bryony Thompson Added comment: Comment on list classification: Monoallelic DCM association is still Amber
Mendeliome v1.1894 LDB3 Bryony Thompson Gene: ldb3 has been classified as Green List (High Evidence).
Mendeliome v1.1893 LDB3 Bryony Thompson Added comment: Comment on mode of inheritance: AD missense variants in LDB3 that affect only short isoforms are associated with skeletal myopathies, while AR LoF variants cause paediatric cardiomyopathy
Mendeliome v1.1893 LDB3 Bryony Thompson Mode of inheritance for gene: LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1892 LDB3 Bryony Thompson reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36253531, 32922198; Phenotypes: dilated cardiomyopathy MONDO:0005021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Marked gene: ELN as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Classified gene: ELN as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.67 ELN Zornitza Stark Gene: eln has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.66 ELN Zornitza Stark gene: ELN was added
gene: ELN was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: ELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ELN were set to Cutis laxa, autosomal dominant, MIM# 123700
Review for gene: ELN was set to GREEN
Added comment: Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Classified gene: EFEMP2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.65 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.64 EFEMP2 Zornitza Stark gene: EFEMP2 was added
gene: EFEMP2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EFEMP2 were set to Cutis laxa, autosomal recessive, type IB MIM# 614437
Review for gene: EFEMP2 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Classified gene: DOCK8 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.63 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.62 DOCK8 Zornitza Stark gene: DOCK8 was added
gene: DOCK8 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: DOCK8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DOCK8 were set to Hyper-IgE recurrent infection syndrome, autosomal recessive, MIM# 243700; Childhood bronchiectasis
Review for gene: DOCK8 was set to GREEN
Added comment: Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Marked gene: CFTR as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.61 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.60 CFTR Zornitza Stark gene: CFTR was added
gene: CFTR was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFTR were set to Cystic fibrosis, MIM# 219700
Review for gene: CFTR was set to GREEN
Added comment: Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Classified gene: CCBE1 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.59 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.58 CCBE1 Zornitza Stark gene: CCBE1 was added
gene: CCBE1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: CCBE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CCBE1 were set to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510
Review for gene: CCBE1 was set to GREEN
Added comment: Sources: Expert list
Autoinflammatory Disorders v1.48 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from Immunodeficiency, MONDO:0021094, TBK1-related, AR; Autoinflammation to Autoinflammation with arthritis and vasculitis, MIM# 620880
Autoinflammatory Disorders v1.47 TBK1 Zornitza Stark reviewed gene: TBK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammation with arthritis and vasculitis, MIM# 620880; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.28 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.34 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, SNUPN-related to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Muscular dystrophy and myopathy_Paediatric v1.33 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1892 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793
Mendeliome v1.1891 SNUPN Zornitza Stark reviewed gene: SNUPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM# 620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.186 NBEAL2 Peter McNaughton gene: NBEAL2 was added
gene: NBEAL2 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: NBEAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBEAL2 were set to PMID: 37349339
Phenotypes for gene: NBEAL2 were set to Immune dysregulation
Review for gene: NBEAL2 was set to GREEN
Added comment: Patients with NBEAL2 deficiency present with ALPS-like disease with autoimmune manifestations including Evans syndrome, chill blain lupus, autoimmune thyroiditis, and/or antiplatelet autoantibodies. Functional data demonstrating that NBEAL2 affects CTLA4 expression regulation.
Sources: Literature
Susceptibility to Viral Infections v0.117 NFATC2 Peter McNaughton gene: NFATC2 was added
gene: NFATC2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to PMID: 38427060
Phenotypes for gene: NFATC2 were set to EBV associated lymphoproliferative disease
Review for gene: NFATC2 was set to RED
Added comment: 12yo girl born to consanguineous parents with EBV associated lymphoproliferation. Initially presented with recurrent chest infections, lung deterioration, chronic wet cough and failure to thrive at the age of 9 and severe hypogammaglobulinaemia. Her elder brother died of lymphoma when he was 5 years old, otherwise family history was unremarkable.
Sources: Literature
Disorders of immune dysregulation v0.186 SH2B3 Peter McNaughton gene: SH2B3 was added
gene: SH2B3 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: SH2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to PMID: 37206266
Phenotypes for gene: SH2B3 were set to Immune
Review for gene: SH2B3 was set to GREEN
Added comment: 2x unrelated patients with haematopoietic manifestations with predominantly myeloproliferative features. Both patients developed clinically significant extra‐haematopoietic multi‐organ autoimmune manifestations throughout life including autoimmune hypothyroidism, autoimmune hepatitis, alopecia areata and autoimmune diabetes mellitus.
Sources: Literature
Disorders of immune dysregulation v0.186 CD274 Peter McNaughton gene: CD274 was added
gene: CD274 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: CD274 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD274 were set to PMID: 38634869
Phenotypes for gene: CD274 were set to Immune dysregulation
Review for gene: CD274 was set to AMBER
Added comment: Two siblings, born to second-degree consanguineous parents of Moroccan descent,
both developed neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk, respectively). One sibling was subsequently diagnosed with asthma at the age of 5 mo, auto-immune hypothyroidism at the age of 3 years, and growth hormone (GH) deficiency at the age of 10 years. He also had mild intellectual disability with delayed language development. By
contrast, his sister had no clinical manifestations other than T1D.
Sources: Literature
Combined Immunodeficiency v1.66 ITPR3 Peter McNaughton gene: ITPR3 was added
gene: ITPR3 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPR3 were set to PMID: 36302985
Phenotypes for gene: ITPR3 were set to Combined Immune deficiency, immune dysregulation
Review for gene: ITPR3 was set to GREEN
Added comment: Three different variants in two unrelated compound heterozygous patients demonstrated impaired IP3-mediated Ca2+ responses in vitro, translating into deficient T-cell activation and
proliferation. P1 was a 12-year-old male patient who presented with combined immunodeficiency with profoundly low numbers of B and T cells and required hematopoietic stem cell transplantation (HSCT) at the age of 6 years. P2 was a 36-year-old male
who presented with recurring immune thrombocytopenia (ITP), requiring splenectomy at the age of 19 years. He subsequently suffered from autoimmune hemolytic anemia, susceptibility to infections, and enteropathy. Hypogammaglobulinemia and low numbers of switched memory B cells led to a diagnosis of CVID and monthly treatment with intravenous
immunoglobulin. The patient did not show signs of neuromuscular disorder.
Authors suggest a partially recessive mode of inheritance with complete defects in these causing embryonic lethality.
Sources: Literature
Disorders of immune dysregulation v0.186 UNC93B1 Peter McNaughton gene: UNC93B1 was added
gene: UNC93B1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: UNC93B1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UNC93B1 were set to PMID: 38869500
Phenotypes for gene: UNC93B1 were set to SLE, chilblain lupus
Mode of pathogenicity for gene: UNC93B1 was set to Other
Review for gene: UNC93B1 was set to GREEN
Added comment: Rare missense substitutions in UNC93B1 in probands from five unrelated kindreds presenting with early onset SLE (two probands) or CBL (three probands). Clinical, genetic, and functional in vitro and ex vivo data demonstrating changes in TLR7/8 signalling and trafficking.
Sources: Literature
Cerebral Palsy v1.364 TRPM3 Clare van Eyk gene: TRPM3 was added
gene: TRPM3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to PMID: 37684057
Phenotypes for gene: TRPM3 were set to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS), MIM#620224)
Review for gene: TRPM3 was set to RED
Added comment: Single case report of child with a likely pathogenic de novo missense variant in the ion transport domain of TRPM3 and neurodevelopmental delay with CP (PMID: 37684057). Cerebral palsy has not previously been reported.
Sources: Literature
Prepair 1000+ v1.65 CEP290 Lucy Spencer reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17345604, 16909394, 24807808, 16682970, 16682973, 27434533, 20690115, 32208788; Phenotypes: CEP290-related ciliopathy MONDO:0100451, Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CDT1 Lucy Spencer reviewed gene: CDT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11992493, 21358631; Phenotypes: Meier-Gorlin syndrome 4 MIM#613804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CD55 Lucy Spencer reviewed gene: CD55: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28657829; Phenotypes: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 CARD11 Lucy Spencer reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36729250, 23561803, 23374270; Phenotypes: Immunodeficiency 11A MIM#615206; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 B3GAT3 Lucy Spencer reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31988067; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM#245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ATM Lauren Rogers reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30137827; Phenotypes: Ataxia-telangiectasia, MIM# 208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.65 ACY1 Zornitza Stark Tag for review tag was added to gene: ACY1.
Prepair 1000+ v1.65 CD81 Zornitza Stark Marked gene: CD81 as ready
Prepair 1000+ v1.65 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.65 CD81 Zornitza Stark Publications for gene: CD81 were set to 20237408
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.64 AIFM1 Zornitza Stark Phenotypes for gene: AIFM1 were changed from Cowchock syndrome, 310490 (3) to Combined oxidative phosphorylation deficiency 6, MIM#300816
Prepair 1000+ v1.63 AK2 Zornitza Stark Marked gene: AK2 as ready
Prepair 1000+ v1.63 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.63 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, 267500 (3) to Reticular dysgenesis MIM# 267500
Prepair 1000+ v1.62 AK2 Zornitza Stark Publications for gene: AK2 were set to
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Gene: aldh3a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.61 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from Sjogren-Larsson syndrome, 270200 (3) to Sjogren-Larsson syndrome (MIM#270200)
Prepair 1000+ v1.60 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome (MIM#270200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Marked gene: ALDH7A1 as ready
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.60 ALDH7A1 Zornitza Stark Phenotypes for gene: ALDH7A1 were changed from Epilepsy, pyridoxine-dependent, 266100 (3) to Epilepsy, early-onset, 4, vitamin B6-dependent MIM #266100
Prepair 1000+ v1.59 ALDH7A1 Zornitza Stark Publications for gene: ALDH7A1 were set to
Prepair 1000+ v1.58 ALG12 Zornitza Stark Marked gene: ALG12 as ready
Prepair 1000+ v1.58 ALG12 Zornitza Stark Gene: alg12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.58 ALG12 Zornitza Stark Phenotypes for gene: ALG12 were changed from Congenital disorder of glycosylation, type Ig, 607143 (3) to Congenital disorder of glycosylation, type Ig MIM# 607143
Prepair 1000+ v1.57 ALG12 Zornitza Stark Publications for gene: ALG12 were set to
Prepair 1000+ v1.56 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Prepair 1000+ v1.56 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.56 ALG3 Zornitza Stark Publications for gene: ALG3 were set to
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.55 ALMS1 Zornitza Stark Phenotypes for gene: ALMS1 were changed from Alstrom syndrome, 203800 (3) to Alstrom syndrome, MIM# 203800
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Marked gene: ALOX12B as ready
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Gene: alox12b has been classified as Green List (High Evidence).
Prepair 1000+ v1.54 ALOX12B Zornitza Stark Phenotypes for gene: ALOX12B were changed from Ichthyosis, congenital, autosomal recessive 2, 242100 (3) to Ichthyosis, congenital, autosomal recessive 2, MIM# 242100
Prepair 1000+ v1.53 ALOX12B Zornitza Stark Publications for gene: ALOX12B were set to
Prepair 1000+ v1.52 ALOX12B Zornitza Stark reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Marked gene: ALOXE3 as ready
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Gene: aloxe3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.52 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from Ichthyosis, congenital, autosomal recessive 3, 606545 (3) to Ichthyosis, congenital, autosomal recessive 3 (MIM#606545)
Prepair 1000+ v1.51 ALOXE3 Zornitza Stark reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 3 (MIM#606545); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Marked gene: ANTXR1 as ready
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Gene: antxr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.51 ANTXR1 Zornitza Stark Phenotypes for gene: ANTXR1 were changed from GAPO syndrome, 230740 (3) to GAPO syndrome (MIM#230740)
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Marked gene: ANTXR2 as ready
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Gene: antxr2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.50 ANTXR2 Zornitza Stark Phenotypes for gene: ANTXR2 were changed from Hyaline fibromatosis syndrome, 228600 (3) to Hyaline fibromatosis syndrome, MIM# 228600; MONDO:0009229
Prepair 1000+ v1.49 ANTXR2 Zornitza Stark Publications for gene: ANTXR2 were set to
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Marked gene: AP4B1 as ready
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Gene: ap4b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.48 AP4B1 Zornitza Stark Publications for gene: AP4B1 were set to
Prepair 1000+ v1.47 AQP2 Zornitza Stark Marked gene: AQP2 as ready
Prepair 1000+ v1.47 AQP2 Zornitza Stark Gene: aqp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.47 AQP2 Zornitza Stark Phenotypes for gene: AQP2 were changed from Diabetes insipidus, nephrogenic, 125800 (3) to Diabetes insipidus, nephrogenic, type 2 MIM# 125800
Prepair 1000+ v1.46 AQP2 Zornitza Stark Publications for gene: AQP2 were set to
Prepair 1000+ v1.45 ARG1 Zornitza Stark Marked gene: ARG1 as ready
Prepair 1000+ v1.45 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.45 ARG1 Zornitza Stark Phenotypes for gene: ARG1 were changed from Argininemia, 207800 (3) to Argininemia MIM# 207800
Prepair 1000+ v1.44 ARG1 Zornitza Stark Publications for gene: ARG1 were set to
Prepair 1000+ v1.43 CD40 Zornitza Stark Marked gene: CD40 as ready
Prepair 1000+ v1.43 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Prepair 1000+ v1.43 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 DBT Zornitza Stark Marked gene: DBT as ready
Prepair 1000+ v1.43 DBT Zornitza Stark Gene: dbt has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 DBT Zornitza Stark reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.43 ARL6 Lauren Rogers edited their review of gene: ARL6: Changed phenotypes: Bardet-Biedl syndrome 3, MIM# 600151, Retinitis pigmentosa 55, MIM#613575
Prepair 1000+ v1.43 CRB1 Lauren Rogers edited their review of gene: CRB1: Changed phenotypes: Leber congenital amaurosis 8 MIM#613835, Retinitis pigmentosa-12, MIM#600105
Prepair 1000+ v1.43 COQ4 Lauren Rogers edited their review of gene: COQ4: Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, MIM#620666
Prepair 1000+ v1.43 COQ4 Lauren Rogers changed review comment from: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Intellectual disability syndromic and non-syndromic v0.6063 SLC39A14 Kushani Jayasinghe reviewed gene: SLC39A14: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27231142, 29685658; Phenotypes: Hypermanganesemia with dystonia 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer edited their review of gene: ALOXE3: Added comment: Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel; Changed rating: GREEN
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel

Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 ALOXE3 Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)

Known technical challenges? Y; to: HGNC approved symbol/name: ALOXE3

Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here.

Treatments available: No specific treatment available (from babyscreen)
Prepair 1000+ v1.43 COL2A1 Lauren Rogers reviewed gene: COL2A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31755234, 32896647; Phenotypes: Spondyloperipheral dysplasia, MIM #271700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.43 COQ4 Lauren Rogers changed review comment from: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Prepair 1000+ v1.43 AP4M1 Zornitza Stark Marked gene: AP4M1 as ready
Prepair 1000+ v1.43 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 AP4S1 Zornitza Stark Marked gene: AP4S1 as ready
Prepair 1000+ v1.43 AP4S1 Zornitza Stark Gene: ap4s1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.43 ARHGEF9 Zornitza Stark Phenotypes for gene: ARHGEF9 were changed from Epileptic encephalopathy, early infantile, 8, 300607 (3) to Developmental and epileptic encephalopathy 8, MIM# 300607
Prepair 1000+ v1.42 ARHGEF9 Zornitza Stark Publications for gene: ARHGEF9 were set to
Prepair 1000+ v1.41 ARHGEF9 Zornitza Stark Tag SV/CNV tag was added to gene: ARHGEF9.
Prepair 1000+ v1.41 ARL6 Zornitza Stark Marked gene: ARL6 as ready
Prepair 1000+ v1.41 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.41 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from Bardet-Biedl syndrome 3, 600151 (3) to Bardet-Biedl syndrome 3, MIM# 600151
Prepair 1000+ v1.40 AIFM1 Lilian Downie Publications for gene: AIFM1 were set to
Prepair 1000+ v1.40 ARL6 Zornitza Stark Publications for gene: ARL6 were set to
Prepair 1000+ v1.39 ARL6 Zornitza Stark changed review comment from: Usually associated with multi-system ciliopathy, ID is a feature.; to: Usually associated with multi-system ciliopathy, ID is usually, though not always, a feature. Note gene is also associated with isolated RP.
Prepair 1000+ v1.39 ARL6 Zornitza Stark reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.39 ARSB Zornitza Stark Marked gene: ARSB as ready
Prepair 1000+ v1.39 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Prepair 1000+ v1.39 ARSB Zornitza Stark Publications for gene: ARSB were set to
Prepair 1000+ v1.38 AGXT Lilian Downie Marked gene: AGXT as ready
Prepair 1000+ v1.38 AGXT Lilian Downie Gene: agxt has been classified as Green List (High Evidence).
Prepair 1000+ v1.38 AGXT Lilian Downie Publications for gene: AGXT were set to
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.37 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from Farber lipogranulomatosis, 228000 (3) to Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950; Farber lipogranulomatosis, MIM#228000
Prepair 1000+ v1.36 AGA Lilian Downie Marked gene: AGA as ready
Prepair 1000+ v1.36 AGA Lilian Downie Gene: aga has been classified as Green List (High Evidence).
Prepair 1000+ v1.36 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950, Farber lipogranulomatosis, MIM#228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.36 AGA Lilian Downie Publications for gene: AGA were set to
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Marked gene: ATP6V1B1 as ready
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Gene: atp6v1b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.35 ATP6V1B1 Zornitza Stark Phenotypes for gene: ATP6V1B1 were changed from Renal tubular acidosis with deafness, 267300 (3) to Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300
Prepair 1000+ v1.34 AGL Lilian Downie Marked gene: AGL as ready
Prepair 1000+ v1.34 AGL Lilian Downie Gene: agl has been classified as Green List (High Evidence).
Prepair 1000+ v1.34 AGL Lilian Downie Publications for gene: AGL were set to
Prepair 1000+ v1.33 ATRX Zornitza Stark Marked gene: ATRX as ready
Prepair 1000+ v1.33 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Prepair 1000+ v1.33 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from ATR-X-related syndrome MONDO:0016980; Mental retardation-hypotonic facies syndrome, X-linked, 309580 (3) to ATR-X-related syndrome MONDO:0016980
Prepair 1000+ v1.32 ATRX Zornitza Stark Publications for gene: ATRX were set to
Prepair 1000+ v1.31 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Prepair 1000+ v1.31 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.31 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, 209900 (3) to Bardet-Biedl syndrome 1, MIM# 209900
Prepair 1000+ v1.30 ADSL Lilian Downie Marked gene: ADSL as ready
Prepair 1000+ v1.30 ADSL Lilian Downie Gene: adsl has been classified as Green List (High Evidence).
Prepair 1000+ v1.30 ADSL Lilian Downie Publications for gene: ADSL were set to
Prepair 1000+ v1.30 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Prepair 1000+ v1.29 BBS1 Zornitza Stark reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.29 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Prepair 1000+ v1.29 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.29 ACTA1 Lilian Downie Marked gene: ACTA1 as ready
Prepair 1000+ v1.29 ACTA1 Lilian Downie Gene: acta1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.29 ACTA1 Lilian Downie Publications for gene: ACTA1 were set to 19562689
Prepair 1000+ v1.28 BBS12 Zornitza Stark reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.28 ACTA1 Lilian Downie Publications for gene: ACTA1 were set to
Prepair 1000+ v1.27 C1QA Zornitza Stark Marked gene: C1QA as ready
Prepair 1000+ v1.27 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Prepair 1000+ v1.27 C1QA Zornitza Stark Publications for gene: C1QA were set to
Prepair 1000+ v1.26 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.26 ACAD9 Lilian Downie Marked gene: ACAD9 as ready
Prepair 1000+ v1.26 ACAD9 Lilian Downie Gene: acad9 has been classified as Green List (High Evidence).
Prepair 1000+ v1.26 ACAD9 Lilian Downie Publications for gene: ACAD9 were set to
Prepair 1000+ v1.25 CD3D Zornitza Stark Marked gene: CD3D as ready
Prepair 1000+ v1.25 CD3D Zornitza Stark Gene: cd3d has been classified as Green List (High Evidence).
Prepair 1000+ v1.25 CD3D Zornitza Stark Phenotypes for gene: CD3D were changed from Immunodeficiency 19, 615617 (3) to Immunodeficiency 19, severe combined MIM# 615617
Prepair 1000+ v1.24 ACO2 Lilian Downie Marked gene: ACO2 as ready
Prepair 1000+ v1.24 ACO2 Lilian Downie Gene: aco2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.24 ACO2 Lilian Downie Publications for gene: ACO2 were set to
Prepair 1000+ v1.23 CLN5 Zornitza Stark Marked gene: CLN5 as ready
Prepair 1000+ v1.23 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.23 CLN5 Zornitza Stark Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 (3) to Ceroid lipofuscinosis, neuronal, 5, MIM# 256731; MONDO:0009745
Prepair 1000+ v1.22 CRB1 Zornitza Stark Marked gene: CRB1 as ready
Prepair 1000+ v1.22 CRB1 Zornitza Stark Gene: crb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.22 CRB1 Zornitza Stark Publications for gene: CRB1 were set to
Prepair 1000+ v1.21 CRB1 Zornitza Stark reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 8, MIM#613835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.21 ACADVL Lilian Downie Marked gene: ACADVL as ready
Prepair 1000+ v1.21 ACADVL Lilian Downie Gene: acadvl has been classified as Green List (High Evidence).
Prepair 1000+ v1.21 GFM1 Lauren Rogers changed review comment from: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V
; to: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available
Prepair 1000+ v1.21 ACADVL Lilian Downie Publications for gene: ACADVL were set to
Prepair 1000+ v1.20 ECHS1 Lauren Rogers changed review comment from: Well established gene-disease association.

Usually presents in infancy.

Treatable-ID – level 4 evidence: valine restriction improves psychomotor/cognitive development/IQ; improves neurological manifestations (incl. neuro-imaging); improves systemic manifestations (PMID: 32642440); to: Well established gene-disease association.

Usually presents in infancy.
Prepair 1000+ v1.20 CTSD Zornitza Stark Marked gene: CTSD as ready
Prepair 1000+ v1.20 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Prepair 1000+ v1.20 CTSD Zornitza Stark reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.20 ABHD5 Lilian Downie Marked gene: ABHD5 as ready
Prepair 1000+ v1.20 ABHD5 Lilian Downie Gene: abhd5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.20 ABHD5 Lilian Downie Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome, 275630 (3) to Chanarin-Dorfman syndrome, MIM#275630
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.19 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from Perlman syndrome, 267000 (3) to Perlman syndrome MIM# 267000
Prepair 1000+ v1.18 ABHD5 Lilian Downie Publications for gene: ABHD5 were set to
Prepair 1000+ v1.17 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Prepair 1000+ v1.16 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Prepair 1000+ v1.16 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.16 GFM1 Lauren Rogers changed review comment from: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V

Detection on NBS would establish diagnosis early and allow palliative treatment; to: Well established gene-disease association.
Onset at birth with death within first months of life
No treatment available

Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V
Prepair 1000+ v1.16 ABCB7 Lilian Downie Marked gene: ABCB7 as ready
Prepair 1000+ v1.16 ABCB7 Lilian Downie Gene: abcb7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.16 ABCB7 Lilian Downie Phenotypes for gene: ABCB7 were changed from Anemia, sideroblastic, with ataxia, 301310 (3) to Anemia, sideroblastic, with ataxia, MIM# 301310
Prepair 1000+ v1.15 ABCB7 Lilian Downie Publications for gene: ABCB7 were set to
Prepair 1000+ v1.14 ABCA12 Lilian Downie Marked gene: ABCA12 as ready
Prepair 1000+ v1.14 ABCA12 Lilian Downie Gene: abca12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.14 HPGD Zornitza Stark Marked gene: HPGD as ready
Prepair 1000+ v1.14 HPGD Zornitza Stark Gene: hpgd has been classified as Green List (High Evidence).
Prepair 1000+ v1.14 HPGD Zornitza Stark Publications for gene: HPGD were set to
Prepair 1000+ v1.13 HPGD Zornitza Stark reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.13 AARS2 Lilian Downie Marked gene: AARS2 as ready
Prepair 1000+ v1.13 AARS2 Lilian Downie Gene: aars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Marked gene: HPSE2 as ready
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Gene: hpse2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.13 HPSE2 Zornitza Stark Phenotypes for gene: HPSE2 were changed from Urofacial syndrome 1, 236730 (3) to Urofacial syndrome 1 MIM#236730
Prepair 1000+ v1.12 HPSE2 Zornitza Stark Publications for gene: HPSE2 were set to
Prepair 1000+ v1.11 HPSE2 Zornitza Stark reviewed gene: HPSE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Urofacial syndrome 1 MIM#236730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.11 AAAS Lilian Downie Marked gene: AAAS as ready
Prepair 1000+ v1.11 AAAS Lilian Downie Gene: aaas has been classified as Green List (High Evidence).
Prepair 1000+ v1.11 AAAS Lilian Downie Publications for gene: AAAS were set to
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.10 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.10 IL1RN Zornitza Stark Marked gene: IL1RN as ready
Prepair 1000+ v1.10 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
Prepair 1000+ v1.10 IL1RN Zornitza Stark Phenotypes for gene: IL1RN were changed from Interleukin 1 receptor antagonist deficiency, 612852 (3) to Interleukin 1 receptor antagonist deficiency, MIM# 612852; Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis, MIM# 61285
Prepair 1000+ v1.9 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Prepair 1000+ v1.9 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 IL7R Zornitza Stark Marked gene: IL7R as ready
Prepair 1000+ v1.9 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 VPS11 Zornitza Stark reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 12 (MIM#616683); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ARSB Kate Scarff reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11668612, 31142378; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACTA1 Michelle Torres reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19562689; Phenotypes: Congenital myopathy 2B, severe infantile, autosomal recessive (MIM#620265); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ARHGEF9 Kate Scarff reviewed gene: ARHGEF9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31942680, 30048823, 29130122, 28620718; Phenotypes: Developmental and epileptic encephalopathy 8, MIM# 300607; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.9 ACO2 Michelle Torres changed review comment from: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.; to: Is the phenotype(s) severe and onset <18yo ? Y

*No clear genotype-phenotype correlation (Fig 1a, PMID: 34056600)

NB: Optic atrophy 9 may also be AD.
Prepair 1000+ v1.9 ARG1 Kate Scarff reviewed gene: ARG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26467175, 2365823, 1598908, 29726057; Phenotypes: Argininemia MIM# 207800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACO2 Michelle Torres changed review comment from: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.; to: Is the phenotype(s) severe and onset <18yo ? Y

NB: Optic atrophy 9 may also be AD.
Prepair 1000+ v1.9 ACO2 Michelle Torres edited their review of gene: ACO2: Changed rating: GREEN
Prepair 1000+ v1.9 ACO2 Michelle Torres reviewed gene: ACO2: Rating: ; Mode of pathogenicity: None; Publications: 34056600; Phenotypes: Infantile cerebellar-retinal degeneration (MIM#614559), Optic atrophy 9 (MIM#616289); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALG12 Kate Scarff changed review comment from: HGNC approved symbol/name: ALG12
Is the phenotype(s) severe and onset <18yo ? Yes
Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood; to: HGNC approved symbol/name: ALG12
Is the phenotype(s) severe and onset <18yo ? Yes
Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood.
No specific treatment at present.
Prepair 1000+ v1.9 AQP2 Kate Scarff reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 7537761, 11536078; Phenotypes: Diabetes insipidus, nephrogenic, type 2 MIM# 125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4B1 Kate Scarff reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21620353, 22290197, 24700674, 24781758; Phenotypes: Spastic paraplegia 47, autosomal recessive MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALG12 Kate Scarff reviewed gene: ALG12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31481313; Phenotypes: Congenital disorder of glycosylation, type Ig MIM# 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Marked gene: PIGA as ready
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.47 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 1 OMIM# 300818 to Paroxysmal nocturnal hemoglobinuria, somatic, MIM# 300818
Bleeding and Platelet Disorders v1.46 PIGA Zornitza Stark Classified gene: PIGA as Red List (low evidence)
Bleeding and Platelet Disorders v1.46 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.45 PIGA Zornitza Stark Tag somatic tag was added to gene: PIGA.
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Marked gene: PROC as ready
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.45 PROC Zornitza Stark Phenotypes for gene: PROC were changed from THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304 to Thrombophilia 3 due to protein C deficiency MIM#176860; Thrombophilia 3 due to protein C deficiency MIM#612304
Bleeding and Platelet Disorders v1.44 PROC Zornitza Stark Classified gene: PROC as Green List (high evidence)
Bleeding and Platelet Disorders v1.44 PROC Zornitza Stark Gene: proc has been classified as Green List (High Evidence).
Cerebral Palsy v1.364 KDM3B Zornitza Stark Marked gene: KDM3B as ready
Cerebral Palsy v1.364 KDM3B Zornitza Stark Gene: kdm3b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.364 KDM3B Zornitza Stark Classified gene: KDM3B as Red List (low evidence)
Cerebral Palsy v1.364 KDM3B Zornitza Stark Gene: kdm3b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Marked gene: ERLIN2 as ready
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Gene: erlin2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Classified gene: ERLIN2 as Red List (low evidence)
Cerebral Palsy v1.363 ERLIN2 Zornitza Stark Gene: erlin2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.362 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Cerebral Palsy v1.362 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.362 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Cerebral Palsy v1.362 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.361 GFAP Zornitza Stark Marked gene: GFAP as ready
Cerebral Palsy v1.361 GFAP Zornitza Stark Gene: gfap has been classified as Red List (Low Evidence).
Cerebral Palsy v1.361 GFAP Zornitza Stark Classified gene: GFAP as Red List (low evidence)
Cerebral Palsy v1.361 GFAP Zornitza Stark Gene: gfap has been classified as Red List (Low Evidence).
Cerebral Palsy v1.360 DHPS Zornitza Stark Marked gene: DHPS as ready
Cerebral Palsy v1.360 DHPS Zornitza Stark Gene: dhps has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.360 DHPS Zornitza Stark Classified gene: DHPS as Amber List (moderate evidence)
Cerebral Palsy v1.360 DHPS Zornitza Stark Gene: dhps has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Marked gene: CYFIP2 as ready
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Gene: cyfip2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Classified gene: CYFIP2 as Red List (low evidence)
Cerebral Palsy v1.359 CYFIP2 Zornitza Stark Gene: cyfip2 has been classified as Red List (Low Evidence).
Mendeliome v1.1891 SPATA5 Zornitza Stark commented on gene: SPATA5: DEFINITIVE by ClinGen.
Prepair 500+ v1.1 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Fetal anomalies v1.255 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Fetal anomalies v1.255 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Fetal anomalies v1.255 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 ADSL Kate Scarff reviewed gene: ADSL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25112391, 1302001, 22180458, 18524658; Phenotypes: Adenylosuccinase deficiency MIM#103050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.358 ACADM Zornitza Stark Publications for gene: ACADM were set to 11263545; 35076175
Cerebral Palsy v1.357 ACADM Zornitza Stark Classified gene: ACADM as Green List (high evidence)
Cerebral Palsy v1.357 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Cerebral Palsy v1.356 ACADM Clare van Eyk reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38843839; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.356 CYFIP2 Clare van Eyk gene: CYFIP2 was added
gene: CYFIP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CYFIP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYFIP2 were set to PMID: 38843839
Phenotypes for gene: CYFIP2 were set to Developmental and epileptic encephalopathy 65, MIM#618008
Review for gene: CYFIP2 was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in CYFIP2 (PMID: 38843839).
Sources: Literature
Cerebral Palsy v1.356 DHPS Clare van Eyk gene: DHPS was added
gene: DHPS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to PMID: 30661771; 38843839
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment (NEDSSWI), MIM#618480
Review for gene: DHPS was set to AMBER
Added comment: NEDSSWI is an autosomal recessive disorder with onset in infancy. In the first case series of 5 patients from 4 families, pregnancy complications including pregnancy-induced hypertension, preeclampsia, oligohydramnios, low blood pressure and premature birth were reported (PMID: 30661771). Patients show global developmental delay and hypotonia, hypertonia, spasticity, or poor coordination. 2 individuals have been reported with a cerebral palsy diagnosis (PMID: 30661771;38843839).
Sources: Literature
Cerebral Palsy v1.356 GFAP Clare van Eyk gene: GFAP was added
gene: GFAP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFAP were set to PMID: 38843839
Phenotypes for gene: GFAP were set to Alexander disease, MIM#203450
Review for gene: GFAP was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in GFAP (PMID: 38843839). Alexander disease has variable onset and progression, with frequent spasticity and ataxia reported.
Sources: Literature
Cerebral Palsy v1.356 GCH1 Clare van Eyk gene: GCH1 was added
gene: GCH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCH1 were set to PMID: 21935284; 1899474; 33875303; 34908184
Phenotypes for gene: GCH1 were set to Dystonia, DOPA-responsive, MIM#128230; Hyperphenylalaninemia, BH4-deficient, B, MIM#233910
Review for gene: GCH1 was set to GREEN
Added comment: Mutations in the GTP cyclohydrolase I gene (GCH1) are associated with early onset dopa-responsive dystonia with or without hyperphenylalaninemia which is frequently clinically diagnosed as cerebral palsy (PMID: 21935284; 1899474; 33875303; 34908184).
Sources: Literature
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mitochondrial disease v0.927 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.33 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Microcephaly v1.269 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Microcephaly v1.269 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Microcephaly v1.269 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Microcephaly v1.269 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.356 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Mendeliome v1.1891 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Mendeliome v1.1891 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New gene name is AFG2A
Mendeliome v1.1891 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mendeliome v1.1891 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Prepair 1000+ v1.9 AGA Lana Giameos reviewed gene: AGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 1703489, 1904874, 8064811, 8946839; Phenotypes: Aspartylglucosaminuria, MIM# 208400, MONDO:0008830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AGL Marta Cifuentes Ochoa commented on gene: AGL: Current Treatment high-fat, high-protein and low-carbohydrate diet with cornstarch supplementation
Bleeding and Platelet Disorders v1.43 PROC Jane Lin gene: PROC was added
gene: PROC was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROC were set to PMID: 2437584; PMID: 7670104; PMID: 10942114; PMID: 28265398
Phenotypes for gene: PROC were set to THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304
Review for gene: PROC was set to GREEN
gene: PROC was marked as current diagnostic
Added comment: Has well established gene-disease association with thrombosis. Biallelic inheritance is rare and there is evidence it is more severe but data is complicated by findings that some patients also have changes in Factor V Leiden so have not selected the option where biallelic inheritance is more severe.
Sources: Expert list
Bleeding and Platelet Disorders v1.43 PIGA Jane Lin gene: PIGA was added
gene: PIGA was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: PIGA was set to Unknown
Publications for gene: PIGA were set to PMID: 9019395; PMID: 28516949
Phenotypes for gene: PIGA were set to PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 1 OMIM# 300818
Review for gene: PIGA was set to RED
gene: PIGA was marked as current diagnostic
Added comment: PIGA variants linked to Paroxysmal nocturnal hemoglobinuria (PNH), clinical features which include thrombosis, but as somatic changes.
Sources: Expert list
Prepair 1000+ v1.9 ATRX Andrew Coventry reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 16813605, 16955409, 15350606, 23681356; Phenotypes: Alpha thalassemia X-linked intellectual disability syndrome MONDO:0010519; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 AARS2 Clare Hunt reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 8, 614096 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL7R Lauren Rogers reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency 104 MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ASAH1 Lucy Spencer reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM#159950, Farber lipogranulomatosis, MIM#; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 IL2RG Lauren Rogers reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, X-linked MIM# 300400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.9 IL1RN Lauren Rogers reviewed gene: IL1RN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Interleukin 1 receptor antagonist deficiency, MIM# 612852, Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis, MIM# 61285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CRB1 Lauren Rogers reviewed gene: CRB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11231775, 11389483, 16543197; Phenotypes: Leber congenital amaurosis 8 MIM#613835; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4S1 Lucy Spencer reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 52, autosomal recessive, MIM#614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HSD17B4 Lauren Rogers reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPSE2 Lauren Rogers reviewed gene: HPSE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25145936, 23313374, 33558177; Phenotypes: Urofacial syndrome 1 MIM#236730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 AP4M1 Lucy Spencer reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 50, autosomal recessive (MIM#612936); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ANTXR1 Lucy Spencer reviewed gene: ANTXR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GAPO syndrome (MIM#230740); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 HPGD Lauren Rogers reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALOXE3 Lucy Spencer reviewed gene: ALOXE3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 3 (MIM#606545); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ALDH3A2 Lucy Spencer reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sjogren-Larsson syndrome (MIM#270200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 ACADVL Lucy Spencer reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: VLCAD deficiency (MIM#201475); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 GFM1 Lauren Rogers reviewed gene: GFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 1, MIM#609060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.9 CD81 Lauren Rogers reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408, 35849269; Phenotypes: Immunodeficiency, common variable, 6, OMIM:613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1891 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Mendeliome v1.1891 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Mendeliome v1.1891 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 C1QA Lauren Rogers reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654842, 9225968, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1890 DCC Zornitza Stark Publications for gene: DCC were set to 20431009; 31697046; 21242494; 28250454; 28250456; 25763452
Mendeliome v1.1889 DCC Zornitza Stark commented on gene: DCC: Third family reported with biallelic variants and scoliosis, PMID 33141514; novel homozygous frameshift variant (p.Asn800Lysfs*11) in three individuals.
Skeletal dysplasia v0.285 DCC Zornitza Stark Marked gene: DCC as ready
Skeletal dysplasia v0.285 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Skeletal dysplasia v0.285 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.284 DCC Zornitza Stark Phenotypes for gene: DCC were changed from Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542; Gaze palsy, familial horizontal, with progressive scoliosis, 2 617542 to Gaze palsy, familial horizontal, with progressive scoliosis, 2, MIM# 617542
Skeletal dysplasia v0.283 DCC Zornitza Stark Publications for gene: DCC were set to 28250456
Skeletal dysplasia v0.282 DCC Zornitza Stark Classified gene: DCC as Green List (high evidence)
Skeletal dysplasia v0.282 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Mendeliome v1.1889 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Mendeliome v1.1889 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Marked gene: SLC6A20 as ready
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Classified gene: SLC6A20 as Red List (low evidence)
Aminoacidopathy v1.128 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Classified gene: SLC25A22 as Green List (high evidence)
Aminoacidopathy v1.127 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Aminoacidopathy v1.126 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Marked gene: SLC7A5 as ready
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Classified gene: SLC7A5 as Red List (low evidence)
Aminoacidopathy v1.125 SLC7A5 Zornitza Stark Gene: slc7a5 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Marked gene: XPNPEP3 as ready
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Classified gene: XPNPEP3 as Green List (high evidence)
Aminoacidopathy v1.124 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Classified gene: SLC1A4 as Green List (high evidence)
Aminoacidopathy v1.123 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Marked gene: PYCR2 as ready
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Classified gene: PYCR2 as Green List (high evidence)
Aminoacidopathy v1.122 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Marked gene: PEPD as ready
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.121 PEPD Zornitza Stark Classified gene: PEPD as Green List (high evidence)
Aminoacidopathy v1.121 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Marked gene: OPLAH as ready
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.120 OPLAH Zornitza Stark Classified gene: OPLAH as Red List (low evidence)
Aminoacidopathy v1.120 OPLAH Zornitza Stark Gene: oplah has been classified as Red List (Low Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Green List (high evidence)
Aminoacidopathy v1.119 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Marked gene: GSR as ready
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.118 GSR Zornitza Stark Classified gene: GSR as Amber List (moderate evidence)
Aminoacidopathy v1.118 GSR Zornitza Stark Gene: gsr has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.117 GRHPR Zornitza Stark Classified gene: GRHPR as Green List (high evidence)
Aminoacidopathy v1.117 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Marked gene: GPX4 as ready
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.116 GPX4 Zornitza Stark Classified gene: GPX4 as Green List (high evidence)
Aminoacidopathy v1.116 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Marked gene: GCLC as ready
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.115 GCLC Zornitza Stark Classified gene: GCLC as Green List (high evidence)
Aminoacidopathy v1.115 GCLC Zornitza Stark Gene: gclc has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Marked gene: GRM6 as ready
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Aminoacidopathy v1.114 GRM6 Zornitza Stark Classified gene: GRM6 as Green List (high evidence)
Aminoacidopathy v1.114 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ABHD5 Lauren Thomas reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.113 GRM6 Sangavi Sivagnanasundram gene: GRM6 was added
gene: GRM6 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM6 were set to 22008250
Phenotypes for gene: GRM6 were set to GRM6-related retinopathy MONDO:0800397
Review for gene: GRM6 was set to GREEN
Added comment: GRM6-related retinopathy is a glutamate neurotransmitter disorders affecting the ON-centre of the retinal ganglion cells.

>5 unrelated families with a night blindness phenotype due to a defective signal transmission at the ON-centre.
Sources: Other
Aminoacidopathy v1.113 SLC25A22 Sangavi Sivagnanasundram gene: SLC25A22 was added
gene: SLC25A22 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC25A22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A22 were set to 15592994; 19780765; 24596948
Phenotypes for gene: SLC25A22 were set to Developmental and epileptic encephalopathy MONDO:0100062
Review for gene: SLC25A22 was set to GREEN
Added comment: Established gene-disease association with reported individuals having impaired mitochondrial glutamate transport.
Three unrelated families reported with three different rare missense variants.
Sources: Other
Aminoacidopathy v1.113 XPNPEP3 Sangavi Sivagnanasundram gene: XPNPEP3 was added
gene: XPNPEP3 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 32660933; 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1 MONDO:0013163
Review for gene: XPNPEP3 was set to GREEN
Added comment: XPNPEP3 is member of the X-pro-aminopeptidases family.

A total of 3 unrelated families (with different variants) reported with abnormal renal function due to an inborn error of peptide metabolism

32660933 - individual case with a rare frameshift variant p.Q241Tfs*13 who also had evidence of an inborn error of peptide metabolism.
Sources: Other
Aminoacidopathy v1.113 PEPD Sangavi Sivagnanasundram gene: PEPD was added
gene: PEPD was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PEPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEPD were set to 2365824; 19308961; 16470701
Phenotypes for gene: PEPD were set to Prolidase deficiency MONDO:0008221
Review for gene: PEPD was set to GREEN
Added comment: Well established gene-disease association with >10 individuals reported with variants in PEPD and a clinical phenotype associated with prolidase deficiency.
Prolidase deficiency is a classified inborn error of amino acid metabolism.
LoF appears to be the mechanism of disease (https://search.clinicalgenome.org/CCID:007640)
Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram edited their review of gene: PYCR2: Changed rating: GREEN
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram changed review comment from: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other; to: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation along with other phenotypes including failure to thrive.

Sources: Other
Aminoacidopathy v1.113 PYCR2 Sangavi Sivagnanasundram gene: PYCR2 was added
gene: PYCR2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR2 were set to 25865492; 27130255
Phenotypes for gene: PYCR2 were set to Hypomyelinating leukodystrophy 10 MONDO:0014632; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: PYCR2 was set to RED
Added comment: Has been reported in 10 consanguineous families with different variants (frameshift, missense, splice). The affected individuals all had neurological clinical presentation however upon biochemical assessment, plasma proline levels were normal (showed no depletion). There is not enough evidence to indicate that these individuals have a phenotype consistent with an inborn error of amino acid metabolism.
Sources: Other
Mendeliome v1.1888 SLC7A5 Sangavi Sivagnanasundram gene: SLC7A5 was added
gene: SLC7A5 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: SLC7A5 was set to Unknown
Publications for gene: SLC7A5 were set to 29884839
Phenotypes for gene: SLC7A5 were set to Large neutral amino acid transporter deficiency (MIM#600182)
Review for gene: SLC7A5 was set to RED
Added comment: Classified an inborn error of amino acid metabolism by IEMbase however more evidence is required to support the gene-disease association.
Sources: Other
Aminoacidopathy v1.113 SLC7A5 Sangavi Sivagnanasundram gene: SLC7A5 was added
gene: SLC7A5 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC7A5 was set to Unknown
Publications for gene: SLC7A5 were set to 29884839
Phenotypes for gene: SLC7A5 were set to Large neutral amino acid transporter deficiency (MIM#600182)
Review for gene: SLC7A5 was set to RED
Added comment: Classified an inborn error of amino acid metabolism by IEMbase however more evidence is required to support the gene-disease association.
Sources: Other
Aminoacidopathy v1.113 SLC6A20 Sangavi Sivagnanasundram gene: SLC6A20 was added
gene: SLC6A20 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: SLC6A20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A20 were set to 36820062; 19033659; 24816252
Phenotypes for gene: SLC6A20 were set to Hyperglycinuria MONDO:0007677
Review for gene: SLC6A20 was set to RED
Added comment: Only one family reported with a rare missense variant and a clinical phenotype consistent with an inborn error of amino acid metabolism.

Cases have been reported in 19033659 and 24816252 however the variant is too common for a mendelian disease.

No other new publications have been released supporting the gene-disease association with relation to evidence of a biochemical abnormality.
Sources: Other
Skeletal dysplasia v0.281 DCC Achchuthan Shanmugasundram reviewed gene: DCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 33141514; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 2, OMIM:617542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo KDM5C frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with KDM5C variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Aminoacidopathy v1.113 NFE2L2 Sangavi Sivagnanasundram gene: NFE2L2 was added
gene: NFE2L2 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia MONDO:0060591; Disorders of glutathione metabolism
Review for gene: NFE2L2 was set to GREEN
Added comment: 4 unrelated patients with de novo missense variants affected with a multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms including an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 GPX4 Sangavi Sivagnanasundram gene: GPX4 was added
gene: GPX4 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GPX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPX4 were set to 24706940; 32827718
Phenotypes for gene: GPX4 were set to Spondylometaphyseal dysplasia, Sedaghatian type MONDO:0009593; Disorders of glutathione metabolism
Review for gene: GPX4 was set to GREEN
Added comment: SSMD is an inborn error of gluthathione metabolism. Reports of four children (two were siblings from a consanguineous family) with SSMD. Parents were unaffected carriers.
LoF is the mechanism of disease.
Sources: Other
Aminoacidopathy v1.113 GSR Sangavi Sivagnanasundram gene: GSR was added
gene: GSR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSR were set to 17185460; 31122244
Phenotypes for gene: GSR were set to Hemolytic anemia due to glutathione reductase deficiency MONDO:0019531; Disorders of glutathione metabolism
Review for gene: GSR was set to AMBER
Added comment: Not an established gene-disease association however there have been reports of two families reported with GR deficiency and there has been a report of functional evidence as well. More concrete evidence of biochemical abnormalities is required to promote the gene to green.
Sources: Other
Aminoacidopathy v1.113 OPLAH Sangavi Sivagnanasundram gene: OPLAH was added
gene: OPLAH was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OPLAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPLAH were set to 27477828; 27604308
Phenotypes for gene: OPLAH were set to 5-oxoprolinase deficiency MONDO:0009825; Disorders of glutathione metabolism
Review for gene: OPLAH was set to RED
Added comment: Variants have been reported in individuals however it appears that this inborn error of glutathione metabolism appears to be of benign nature.
Sources: Other
Mendeliome v1.1888 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNA seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Aminoacidopathy v1.113 GCLC Sangavi Sivagnanasundram gene: GCLC was added
gene: GCLC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GCLC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCLC were set to 28571779; 10515893; 18024385
Phenotypes for gene: GCLC were set to Gamma-glutamylcysteine synthetase deficiency MONDO:0009259; Disorders of glutathione metabolism
Review for gene: GCLC was set to GREEN
Added comment: Established gene-disease association with >3 unrelated probands reported with GCLC deficiency which is an inborn error of amino acid metabolism.
Sources: Other
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Classified gene: SLC25A15 as Green List (high evidence)
Aminoacidopathy v1.113 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Marked gene: SLC36A2 as ready
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Classified gene: SLC36A2 as Red List (low evidence)
Aminoacidopathy v1.112 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Marked gene: SLC38A8 as ready
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Classified gene: SLC38A8 as Green List (high evidence)
Aminoacidopathy v1.111 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Marked gene: SLC3A1 as ready
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Classified gene: SLC3A1 as Green List (high evidence)
Aminoacidopathy v1.110 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Classified gene: SLC6A19 as Green List (high evidence)
Aminoacidopathy v1.109 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Marked gene: SLC6A6 as ready
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Classified gene: SLC6A6 as Amber List (moderate evidence)
Aminoacidopathy v1.108 SLC6A6 Zornitza Stark Gene: slc6a6 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Classified gene: SLC6A8 as Green List (high evidence)
Aminoacidopathy v1.107 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Marked gene: SLC7A7 as ready
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Classified gene: SLC7A7 as Green List (high evidence)
Aminoacidopathy v1.106 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Marked gene: SLC7A9 as ready
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Classified gene: SLC7A9 as Green List (high evidence)
Aminoacidopathy v1.105 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Marked gene: SPR as ready
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.104 SPR Zornitza Stark Classified gene: SPR as Green List (high evidence)
Aminoacidopathy v1.104 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Marked gene: SUGCT as ready
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.103 SUGCT Zornitza Stark Classified gene: SUGCT as Amber List (moderate evidence)
Aminoacidopathy v1.103 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Marked gene: SUOX as ready
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.102 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Aminoacidopathy v1.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Marked gene: TAT as ready
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.101 TAT Zornitza Stark Classified gene: TAT as Green List (high evidence)
Aminoacidopathy v1.101 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Marked gene: TDO2 as ready
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.100 TDO2 Zornitza Stark Classified gene: TDO2 as Red List (low evidence)
Aminoacidopathy v1.100 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Marked gene: TH as ready
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.99 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Aminoacidopathy v1.99 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Marked gene: TYR as ready
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.98 TYR Zornitza Stark Classified gene: TYR as Green List (high evidence)
Aminoacidopathy v1.98 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Aminoacidopathy v1.97 GRHPR Sangavi Sivagnanasundram gene: GRHPR was added
gene: GRHPR was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRHPR were set to 24116921
Phenotypes for gene: GRHPR were set to primary hyperoxaluria type 2 MONDO:0009824; Disorders of glyoxylate and oxalate metabolism
Review for gene: GRHPR was set to GREEN
Added comment: Well established gene - disease association with reported individuals having abnormal biochemical function.
Sources: Other
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.328 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.327 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Marked gene: ZNF483 as ready
Mendeliome v1.1888 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1888 ZNF483 Zornitza Stark Mode of inheritance for gene: ZNF483 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1887 ZNF483 Zornitza Stark Classified gene: ZNF483 as Amber List (moderate evidence)
Mendeliome v1.1887 ZNF483 Zornitza Stark Gene: znf483 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Marked gene: UROC1 as ready
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.97 UROC1 Zornitza Stark Classified gene: UROC1 as Amber List (moderate evidence)
Aminoacidopathy v1.97 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.65 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Classified gene: HOGA1 as Green List (high evidence)
Aminoacidopathy v1.96 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.95 HOGA1 Sangavi Sivagnanasundram gene: HOGA1 was added
gene: HOGA1 was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 26401545; 21896830; 20797690
Phenotypes for gene: HOGA1 were set to primary hyperoxaluria type 3 MONDO:0013327; Disorders of ornithine, proline and hydroxyproline metabolism
Review for gene: HOGA1 was set to GREEN
Added comment: Established gene-disease association with >4 unrelated individuals having evidence of abnormal biochemical function.
Sources: Other
Cerebellar and Pontocerebellar Hypoplasia v1.64 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Microcephaly v1.268 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6062 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: CRNKL1 were set to Complete
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Aminoacidopathy v1.95 UROC1 Sangavi Sivagnanasundram gene: UROC1 was added
gene: UROC1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: UROC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROC1 were set to 19304569; 30619714; 32439973; 27391121
Phenotypes for gene: UROC1 were set to urocanic aciduria MONDO:0010167
Review for gene: UROC1 was set to AMBER
Added comment: The relationship between the phenotypes and evidence of biochemical abnormality remains unclear for this gene-disease association.

Variants have been reported in 4 unrelated individuals however one individual was reported to be phenotypically asymptomatic except for evidence of urocanase deficiency in a biochemical assay (PMID: 30619714).

Classified Moderate by Aminoacidopathy GCEP on 26/04/2024 - https://search.clinicalgenome.org/CCID:006504
Sources: ClinGen
Mendeliome v1.1886 ZNF483 Mark Cleghorn gene: ZNF483 was added
gene: ZNF483 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF483 was set to Unknown
Publications for gene: ZNF483 were set to 38951643
Phenotypes for gene: ZNF483 were set to primary ovarian failure MONDO:0005387
Review for gene: ZNF483 was set to AMBER
Added comment: PMID: 38951643, ESHG 2024 presentation
Large cohort assessing PRS for age of menarche
Noted rare PTVs in ZNF483 assoc w earlier menarche
No individual case information in this study
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.326 ZNF483 Mark Cleghorn gene: ZNF483 was added
gene: ZNF483 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: ZNF483 was set to Unknown
Publications for gene: ZNF483 were set to 38951643
Phenotypes for gene: ZNF483 were set to primary ovarian failure MONDO:0005387
Penetrance for gene: ZNF483 were set to unknown
Review for gene: ZNF483 was set to AMBER
Added comment: PMID: 38951643, ESHG 2024 presentation
Large cohort assessing PRS for age of menarche
Noted rare PTVs in ZNF483 assoc w earlier menarche
No individual case information in this study
Sources: Literature
Aminoacidopathy v1.95 TYR Sangavi Sivagnanasundram gene: TYR was added
gene: TYR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TYR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYR were set to 2511845; 32411182; 31199599; 29052256
Phenotypes for gene: TYR were set to oculocutaneous albinism type 1 MONDO:0018135
Review for gene: TYR was set to GREEN
Added comment: TYR encodes tyrosinase which vital in melanin synthesis. Reported individuals have an error in tyrosinase metabolism thus affecting melanin synthesis. >5 probands have been reported with errors in tyrosinase metabolism.

Classified Definitive by Aminoacidopathy GCEP on 28/08/2020 - https://search.clinicalgenome.org/CCID:006490
Sources: ClinGen
Aminoacidopathy v1.95 TH Sangavi Sivagnanasundram gene: TH was added
gene: TH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 30383639; 29225908; 22264700; 12891655
Phenotypes for gene: TH were set to tyrosine hydroxylase deficiency MONDO:0100064
Review for gene: TH was set to GREEN
Added comment: >10 unrelated probands reported with an inborn error in tyrosine metabolism.

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006363
Sources: ClinGen
Aminoacidopathy v1.95 TDO2 Sangavi Sivagnanasundram gene: TDO2 was added
gene: TDO2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TDO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDO2 were set to 28285122
Phenotypes for gene: TDO2 were set to familial hypertryptophanemia MONDO:0010907
Review for gene: TDO2 was set to RED
Added comment: Reported in one individual to date however there is evidence that this is a benign biochemical variant with no clinical significance.

Classified Limitied by Aminoacidopathy GCEP on 17/11/2023 - https://search.clinicalgenome.org/CCID:006345
Sources: ClinGen
Aminoacidopathy v1.95 TAT Sangavi Sivagnanasundram gene: TAT was added
gene: TAT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 9544843; 16917729
Phenotypes for gene: TAT were set to tyrosinemia type II MONDO:0010160
Review for gene: TAT was set to GREEN
Added comment: Well reported gene-disease association with affected individuals having reports of a deficiency in hepatic tyrosine aminotransferase (TAT).

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006320
Sources: ClinGen
Aminoacidopathy v1.95 SUOX Sangavi Sivagnanasundram gene: SUOX was added
gene: SUOX was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 28980090
Phenotypes for gene: SUOX were set to isolated sulfite oxidase deficiency MONDO:0010089
Review for gene: SUOX was set to GREEN
Added comment: Well established gene-disease association (reported in >40 patients).

Classified Definitive by Aminoacidopathy GCEP on 22/03/2019 - https://search.clinicalgenome.org/CCID:006301
Sources: ClinGen
Aminoacidopathy v1.95 SUGCT Sangavi Sivagnanasundram gene: SUGCT was added
gene: SUGCT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SUGCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUGCT were set to 18926513; 28766179; 29421601
Phenotypes for gene: SUGCT were set to glutaric acidemia type 3 MONDO:0009283
Review for gene: SUGCT was set to AMBER
Added comment: There is uncertain clinical relevance for this gene-disease association - reports of different clinical phenotypes between affected individuals and potentially a benign condition. Variants have been reported in >3 unrelated affected probands however their clinical presentations vary.

Classified Moderate by Aminoacidopathy GCEP on 12/12/2022- https://search.clinicalgenome.org/CCID:006299
Sources: ClinGen
Aminoacidopathy v1.95 SPR Sangavi Sivagnanasundram gene: SPR was added
gene: SPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPR were set to 33903016
Phenotypes for gene: SPR were set to dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Review for gene: SPR was set to GREEN
Added comment: Well-established gene-disease association with reported individuals having an inborn error of amino acid metabolism.

Classified Definitive by Aminoacidopathy GCEP on 04/06/2021- https://search.clinicalgenome.org/CCID:006266
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A9 Sangavi Sivagnanasundram gene: SLC7A9 was added
gene: SLC7A9 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A9 were set to 23532419; 16609684; 25296721; 11157794; 10471498
Phenotypes for gene: SLC7A9 were set to cystinuria MONDO:0009067
Review for gene: SLC7A9 was set to GREEN
Added comment: Established gene-disease association with reported individuals having errors in amino acid transport and metabolism.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006202
Sources: ClinGen
Aminoacidopathy v1.95 SLC7A7 Sangavi Sivagnanasundram gene: SLC7A7 was added
gene: SLC7A7 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A7 were set to 10080182; 10080183; 15776247
Phenotypes for gene: SLC7A7 were set to lysinuric protein intolerance MONDO:0009109
Review for gene: SLC7A7 was set to GREEN
Added comment: Reported in at least 8 probands all having an error in amino acid transport. LoF is the mechanism of disease.

Classified Definitive by Aminoacidopathy GCEP on 08/11/2019 - https://search.clinicalgenome.org/CCID:006201
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A8 Sangavi Sivagnanasundram gene: SLC6A8 was added
gene: SLC6A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC6A8 were set to 27604308; 16738945
Phenotypes for gene: SLC6A8 were set to creatine transporter deficiency MONDO:0010305
Review for gene: SLC6A8 was set to GREEN
Added comment: Well-established gene disease association with reported individuals having error in creatine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2020 - https://search.clinicalgenome.org/CCID:006200
Sources: ClinGen
Aminoacidopathy v1.95 SLC6A6 Sangavi Sivagnanasundram gene: SLC6A6 was added
gene: SLC6A6 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31903486; 31345061
Phenotypes for gene: SLC6A6 were set to hypotaurinemic retinal degeneration and cardiomyopathy MONDO:0007777
Review for gene: SLC6A6 was set to AMBER
Added comment: 4 individuals reported with retinal degeneration while 2 (who are siblings) also reported cardiomyopathy. The proband (one of the siblings) was given oral taurine supplementation that reversed their phenotype (cardiomyopathy was reversed and the retinal degeneration was halted) (PMID: 31903486).

Classified Limited by Aminoacidopathy GCEP on 10/03/2023 - https://search.clinicalgenome.org/CCID:006199
Sources: ClinGen
Prepair 1000+ v1.9 ETFDH Lilian Downie Marked gene: ETFDH as ready
Prepair 1000+ v1.9 ETFDH Lilian Downie Gene: etfdh has been classified as Green List (High Evidence).
Prepair 1000+ v1.9 ETFDH Lilian Downie Publications for gene: ETFDH were set to 31904027
Prepair 1000+ v1.8 ETFDH Lilian Downie Publications for gene: ETFDH were set to
Aminoacidopathy v1.95 SLC6A19 Sangavi Sivagnanasundram gene: SLC6A19 was added
gene: SLC6A19 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC6A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A19 were set to 15286787; 15286788; 18484095
Phenotypes for gene: SLC6A19 were set to Hartnup disease MONDO:0009324
Review for gene: SLC6A19 was set to GREEN
Added comment: Established gene-disease association with >10 probands reported with clinical symptoms assocation with Hartnup disease. Mechanism of disease is LoF with affected individuals having a defect in amino acid transportation.

Classified Definitive by Aminoacidopathy GCEP on 07/05/2020 - https://search.clinicalgenome.org/CCID:006196
Sources: ClinGen
Aminoacidopathy v1.95 SLC3A1 Sangavi Sivagnanasundram gene: SLC3A1 was added
gene: SLC3A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC3A1 were set to 8054986; 16374432; 8486766
Phenotypes for gene: SLC3A1 were set to cystinuria MONDO:0009067
Review for gene: SLC3A1 was set to GREEN
Added comment: Established gene-disease association with reported individuals having biochemical abnormalities affecting cystine transportation.

Classified Definitive by Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:006188
Sources: ClinGen
Aminoacidopathy v1.95 SLC38A8 Sangavi Sivagnanasundram gene: SLC38A8 was added
gene: SLC38A8 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC38A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A8 were set to 32744312; 24290379; 24045842; 25451601; 24290379
Phenotypes for gene: SLC38A8 were set to foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216
Review for gene: SLC38A8 was set to GREEN
Added comment: Reported in >5 unrelated probands with reported errors in glutamate/glutamine transport.

Classified Definitive by Aminoacidopathy GCEP on 10/02/2023 - https://search.clinicalgenome.org/CCID:006184
Sources: ClinGen
Aminoacidopathy v1.95 SLC36A2 Sangavi Sivagnanasundram gene: SLC36A2 was added
gene: SLC36A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC36A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC36A2 were set to 19033659; 26141664
Phenotypes for gene: SLC36A2 were set to iminoglycinuria MONDO:0009448
Review for gene: SLC36A2 was set to RED
Added comment: IG phenotype is due to excess urinary excretion of proline, hydroxyproline and glycine which is thought to be benign. Variants have been reported in individuals with varying phenotypes - One homozygous individual reported with an IG phenotype while some heterozygous individuals reported to have hyperglycinuria. Biochemical abnormalities result in an IG phenotype is not a common clinical feature in the reported individuals.

Classified Limitied by Aminoacidopathy GCEP on 11/04/2024 - https://search.clinicalgenome.org/CCID:006183
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A15 Sangavi Sivagnanasundram gene: SLC25A15 was added
gene: SLC25A15 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A15 were set to 25874378
Phenotypes for gene: SLC25A15 were set to ornithine translocase deficiency MONDO:0009393 (HHH Syndrome)
Review for gene: SLC25A15 was set to GREEN
Added comment: Well established gene-disease association with reported individuals presenting with a biochemical triad of abnormalities - hyperornithinemia, hyperammonemia, and homocitrullinuria (severity of the clinical symptoms can vary).

Common variants in individuals with HHH syndrome
p.Phe188del
French Canadian Founder - NFE GrpMax AF - 0.004% (reported in 62 hets globally)

p.Arg179X
Commonly seen in Japanese patients - EAS GrpMax AF - 0.017% (reported in 26 hets globally)

Classified Definitive by Aminoacidopathy GCEP on 04/12/2019 -https://search.clinicalgenome.org/CCID:006162
Sources: ClinGen
Aminoacidopathy v1.95 SLC25A13 Sangavi Sivagnanasundram gene: SLC25A13 was added
gene: SLC25A13 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A13 were set to 18367750; 10369257; 19036621; 18392553; 11343053; 31607264
Phenotypes for gene: SLC25A13 were set to citrin deficiency MONDO:0016602
Review for gene: SLC25A13 was set to GREEN
Added comment: Established gene-disease association with variants reported in >10 probands with reported biochemical abnormalities. Variants in this gene have been reported in both adult onset citrullinemia type 2 but also in individuals with neonatal intrahepatic cholestasis.

Mechanism of disease is biallelic loss of function - significantly reduced or absent glutamate transport in and aspartate transport out of mitochondria depriving argininosuccinate synthetase leading to the accumulation of citrulline and ammonia.

Classified Definitive by Aminoacidopathy GCEP on 23/07/2021 - https://search.clinicalgenome.org/CCID:006161
Sources: ClinGen
Aminoacidopathy v1.95 SLC1A4 Sangavi Sivagnanasundram gene: SLC1A4 was added
gene: SLC1A4 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A4 were set to 25930971, 27711071, 29989513, 29652076, 26041762, 27193218, 30125339
Phenotypes for gene: SLC1A4 were set to spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome MONDO:0014725
Review for gene: SLC1A4 was set to GREEN
Added comment: Reported in at least 9 individuals with reported biochemical abnormalities involving the L-serine transporter.

Classified Definitive by Aminoacidopathy GCEP on 14/05/2021 - https://search.clinicalgenome.org/CCID:006155
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.6062 B9D1 Achchuthan Shanmugasundram reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 32622957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram changed review comment from: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient. T; to: PMID:34462534 reported the identification of homozygous DDOST variant (c.1187G>A) in a Chinese patient who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in the patient.
Congenital Disorders of Glycosylation v1.44 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1886 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ETFDH Lauren Rogers reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904027; Phenotypes: Glutaric acidemia IIC, MIM# 231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ECHS1 Lauren Rogers reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32642440; Phenotypes: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DIS3L2 Lauren Rogers reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22306653, 28328139, 29950491; Phenotypes: Perlman syndrome MIM# 267000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 DBT Lauren Rogers reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type II (MIM#248600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP7B Andrew Coventry reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35042319 8298639 9554743 10790207 7626145 16133174 28433102; Phenotypes: Wilson disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALG3 Andrew Coventry reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067009, 10581255, 15840742; Phenotypes: Congenital disorder of glycosylation, type Id; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.0 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: GREEN; Changed publications: 29463886, 32346159, 36117209
Speech apraxia v1.0 SETD1A Thomas Scerri changed review comment from: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Kaspi et al. (2022; PMID: 36117209) report a CAS proband with a de novo SETD1A splice acceptor variant.

An independent (unpublished) in-house CAS proband has a de novo SETD1A frameshift variant.

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Marked gene: FNIP1 as ready
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Classified gene: FNIP1 as Green List (high evidence)
Predominantly Antibody Deficiency v0.135 FNIP1 Zornitza Stark Gene: fnip1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Marked gene: SENP7 as ready
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Predominantly Antibody Deficiency v0.134 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.133 SENP7 Zornitza Stark gene: SENP7 was added
gene: SENP7 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to 38972567
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to GREEN
Added comment: 4 individuals from three unrelated families reported with biallelic variants and neurodevelopmental abnormalities, dysmorphism, and immunodeficiency, including hypogammaglobulinaemia.
Sources: Literature
Mendeliome v1.1886 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Mendeliome v1.1885 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Mendeliome v1.1885 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Mendeliome v1.1884 SENP7 Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567, 37460201; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.29 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201; 38972567
Phagocyte Defects v1.28 SENP7 Zornitza Stark Publications for gene: SENP7 were set to PMID: 37460201
Phagocyte Defects v1.27 SENP7 Zornitza Stark Classified gene: SENP7 as Green List (high evidence)
Phagocyte Defects v1.27 SENP7 Zornitza Stark Gene: senp7 has been classified as Green List (High Evidence).
Phagocyte Defects v1.26 SENP7 Zornitza Stark reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38972567; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1884 MYZAP Zornitza Stark changed review comment from: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature; to: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

The MYZAP gene is part of the GRINL1A complex transcription unit (CTU), or GCOM1, which also includes the downstream POLR2M gene, or GRINL1A.. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.

Transcription from an upstream promoter within the GRINL1A CTU produces 2 types of alternatively spliced transcripts: MYZAP transcripts, also called GRINL1A upstream (GUP) transcripts, which include only exons from the MYZAP gene, and GRINL1A combined (GCOM) transcripts, which include exons from both the MYZAP gene and the downstream POLR2M gene. Transcription of the POLR2M gene initiates at a downstream promoter within the GRINL1A CTU and produces alternatively spliced POLR2M transcripts, also called GRINL1A downstream (GDOWN) transcripts, which include only exons from the POLR2M gene
Sources: Literature
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark changed review comment from: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature; to: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

The MYZAP gene is part of the GRINL1A complex transcription unit (CTU), or GCOM1, which also includes the downstream POLR2M gene, or GRINL1A.. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.

Transcription from an upstream promoter within the GRINL1A CTU produces 2 types of alternatively spliced transcripts: MYZAP transcripts, also called GRINL1A upstream (GUP) transcripts, which include only exons from the MYZAP gene, and GRINL1A combined (GCOM) transcripts, which include exons from both the MYZAP gene and the downstream POLR2M gene. Transcription of the POLR2M gene initiates at a downstream promoter within the GRINL1A CTU and produces alternatively spliced POLR2M transcripts, also called GRINL1A downstream (GDOWN) transcripts, which include only exons from the POLR2M gene
Sources: Literature
Mendeliome v1.1884 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Mendeliome v1.1884 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Mendeliome v1.1884 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Mendeliome v1.1883 MYZAP Zornitza Stark gene: MYZAP was added
gene: MYZAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627
Phenotypes for gene: MYZAP were set to Cardiomyopathy, dilated, 2K, MIM# 620894
Review for gene: MYZAP was set to GREEN
Added comment: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model. Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Marked gene: MYZAP as ready
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Classified gene: MYZAP as Green List (high evidence)
Dilated Cardiomyopathy v1.33 MYZAP Zornitza Stark Gene: myzap has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.32 MYZAP Zornitza Stark gene: MYZAP was added
gene: MYZAP was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627
Phenotypes for gene: MYZAP were set to Cardiomyopathy, dilated, 2K, MIM# 620894
Review for gene: MYZAP was set to GREEN
Added comment: 10 individuals from four unrelated families with bi-allelic variants in this gene with DCM. Supportive zebrafish model.

Note the MYZAP and GCOM1 genes are part of the GRINL1A complex transcription unit. Some of the reported variants affect GCOM1 with postulated effect on MYZAP due to read through transcription (two families), and in the rest of the families MYZAP was affected directly.
Sources: Literature
Prepair 1000+ v1.7 AFF2 Lauren Rogers reviewed gene: AFF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35431806, 8334699, 21739600, 22773736; Phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ALDH7A1 Andrew Coventry reviewed gene: ALDH7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16491085, 17068770, 32969477, 33200442, 17721876, 19142996, 22784480, 29053735; Phenotypes: Epilepsy, early-onset, 4, vitamin B6-dependent MIM #266100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AK2 Andrew Coventry reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AGXT Andrew Coventry reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957, 33789010; Phenotypes: Hyperoxaluria, primary, type 1 MIM #259900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Marked gene: PCBD1 as ready
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Classified gene: PCBD1 as Green List (high evidence)
Aminoacidopathy v1.94 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Marked gene: PAH as ready
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.93 PAH Zornitza Stark Classified gene: PAH as Green List (high evidence)
Aminoacidopathy v1.93 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Marked gene: OTC as ready
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.92 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Aminoacidopathy v1.92 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Marked gene: OAT as ready
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.91 OAT Zornitza Stark Classified gene: OAT as Green List (high evidence)
Aminoacidopathy v1.91 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.90 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Aminoacidopathy v1.90 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Marked gene: NAGS as ready
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.89 NAGS Zornitza Stark Classified gene: NAGS as Green List (high evidence)
Aminoacidopathy v1.89 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Marked gene: MTRR as ready
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.88 MTRR Zornitza Stark Classified gene: MTRR as Green List (high evidence)
Aminoacidopathy v1.88 MTRR Zornitza Stark Gene: mtrr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Marked gene: MTR as ready
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.87 MTR Zornitza Stark Classified gene: MTR as Green List (high evidence)
Aminoacidopathy v1.87 MTR Zornitza Stark Gene: mtr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.86 MTHFR Zornitza Stark Classified gene: MTHFR as Green List (high evidence)
Aminoacidopathy v1.86 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Marked gene: MPST as ready
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.85 MPST Zornitza Stark Classified gene: MPST as Red List (low evidence)
Aminoacidopathy v1.85 MPST Zornitza Stark Gene: mpst has been classified as Red List (Low Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.84 MMACHC Zornitza Stark Classified gene: MMACHC as Green List (high evidence)
Aminoacidopathy v1.84 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Marked gene: MCEE as ready
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.83 MCEE Zornitza Stark Classified gene: MCEE as Green List (high evidence)
Aminoacidopathy v1.83 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Aminoacidopathy v1.82 MAT1A Zornitza Stark Classified gene: MAT1A as Green List (high evidence)
Aminoacidopathy v1.82 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.16 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 35411967
Prepair 1000+ v1.7 CTSD Lauren Rogers reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.7 ABCB7 Andrew Coventry Deleted their review
Prepair 1000+ v1.7 ABCB7 Andrew Coventry changed review comment from: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.; to: HGNC approved symbol/name: ABCB7
Reported cases of ataxia are typically childhood onset and progressive, anaemia reported to be mostly mild.
Prepair 1000+ v1.7 COQ4 Lauren Rogers reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCB7 Andrew Coventry reviewed gene: ABCB7: Rating: ; Mode of pathogenicity: None; Publications: 10196363, 33157103, 31772327, 31511561, 26242992, 34354969, 22398176; Phenotypes: Anaemia, sideroblastic, with ataxia MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia - adult onset v1.15 PNPT1 Chris Ciotta reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37935417; Phenotypes: Spinocerebellar ataxia 25 (MIM#608703); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.7 AGL Marta Cifuentes Ochoa reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26885414, 20301788, 35834487, 27106217; Phenotypes: Glycogen storage disease IIIa and IIIb, MIM#232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACY1 Marta Cifuentes Ochoa reviewed gene: ACY1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16274666, 16465618, 17562838, 24117009, 37523070, 29653693, 26686503; Phenotypes: Aminoacylase 1 deficiency, MIM# 609924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.7 AIFM1 Karina Sandoval reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362274, 22019070, 26173962, 31523922, 31783324, 28299359, 25934856, 28842795, 28842795; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Marked gene: BRCC3 as ready
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Gene: brcc3 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v0.39 BRCC3 Zornitza Stark Publications for gene: BRCC3 were set to 21596366
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark changed review comment from: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.; to: PMID 21596366: three unrelated families with multiple affected males segregating a deletion involving MTCP1 and BRCC3. Positional approach used. Supportive zebrafish model, knockdown of BRCC3; angiogenesis affected.

PMID 33868155, additional report of affected male, with similar deletion.

No reports of SNVs identified, including in ClinVar.
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark edited their review of gene: BRCC3: Changed rating: RED
Cerebral vascular malformations v0.38 BRCC3 Zornitza Stark reviewed gene: BRCC3: Rating: ; Mode of pathogenicity: None; Publications: 21596366, 33868155; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Classified gene: MAP2K1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.195 MAP2K1 Chirag Patel Gene: map2k1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Classified gene: BRAF as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 BRAF Chirag Patel Gene: braf has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Classified gene: RAF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.194 RAF1 Chirag Patel Gene: raf1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Classified gene: PTPN11 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.193 PTPN11 Chirag Patel Gene: ptpn11 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.193 MAP2K1 Chirag Patel gene: MAP2K1 was added
gene: MAP2K1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to PMID: 20301557
Phenotypes for gene: MAP2K1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 615279
Review for gene: MAP2K1 was set to GREEN
gene: MAP2K1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.192 RAF1 Chirag Patel gene: RAF1 was added
gene: RAF1 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAF1 were set to PMID: 20301557
Phenotypes for gene: RAF1 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 611554
Review for gene: RAF1 was set to GREEN
gene: RAF1 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 PTPN11 Chirag Patel gene: PTPN11 was added
gene: PTPN11 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to PMID: 20301557, 32737134
Phenotypes for gene: PTPN11 were set to Noonan Syndrome with Multiple Lentigines, OMIM # 151100
Review for gene: PTPN11 was set to GREEN
gene: PTPN11 was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Deafness_IsolatedAndComplex v1.191 BRAF Chirag Patel gene: BRAF was added
gene: BRAF was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to PMID: 20301557
Phenotypes for gene: BRAF were set to Noonan Syndrome with Multiple Lentigines, OMIM # 613707
Review for gene: BRAF was set to GREEN
gene: BRAF was marked as current diagnostic
Added comment: Established gene-disease association.
Sensorineural hearing loss is present in ~20% of 'Noonan Syndrome with Multiple Lentigines'
Sources: Literature
Aminoacidopathy v1.81 PHGDH Zornitza Stark Classified gene: PHGDH as Green List (high evidence)
Aminoacidopathy v1.81 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Marked gene: PHYKPL as ready
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Aminoacidopathy v1.80 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Marked gene: PRODH as ready
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.79 PRODH Zornitza Stark Classified gene: PRODH as Green List (high evidence)
Aminoacidopathy v1.79 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Aminoacidopathy v1.78 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Marked gene: PRODH2 as ready
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Mendeliome v1.1882 PRODH2 Zornitza Stark Classified gene: PRODH2 as Red List (low evidence)
Mendeliome v1.1882 PRODH2 Zornitza Stark Gene: prodh2 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Classified gene: PSAT1 as Green List (high evidence)
Aminoacidopathy v1.77 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Marked gene: PSPH as ready
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.76 PSPH Zornitza Stark Classified gene: PSPH as Green List (high evidence)
Aminoacidopathy v1.76 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Marked gene: PTS as ready
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.75 PTS Zornitza Stark Classified gene: PTS as Green List (high evidence)
Aminoacidopathy v1.75 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Classified gene: PYCR1 as Green List (high evidence)
Aminoacidopathy v1.74 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Marked gene: QDPR as ready
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.73 QDPR Zornitza Stark Classified gene: QDPR as Green List (high evidence)
Aminoacidopathy v1.73 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Marked gene: SARDH as ready
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.72 SARDH Zornitza Stark Classified gene: SARDH as Red List (low evidence)
Aminoacidopathy v1.72 SARDH Zornitza Stark Gene: sardh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Aminoacidopathy v1.71 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Marked gene: SELENBP1 as ready
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1881 SELENBP1 Zornitza Stark Classified gene: SELENBP1 as Green List (high evidence)
Mendeliome v1.1881 SELENBP1 Zornitza Stark Gene: selenbp1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Aminoacidopathy v1.70 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Marked gene: SLC1A1 as ready
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Classified gene: SLC1A1 as Amber List (moderate evidence)
Aminoacidopathy v1.69 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Green List (high evidence)
Aminoacidopathy v1.68 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Green List (high evidence)
Aminoacidopathy v1.67 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Green List (High Evidence).
Mendeliome v1.1880 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Mendeliome v1.1879 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Intellectual disability syndromic and non-syndromic v0.6062 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Intellectual disability syndromic and non-syndromic v0.6061 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Ataxia - adult onset v1.15 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - adult onset v1.15 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Marked gene: FDXR as ready
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.26 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Ataxia - paediatric v1.26 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Ataxia - paediatric v1.25 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 33348459; 37046037; 37481223
Phenotypes for gene: FDXR were set to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Review for gene: FDXR was set to GREEN
Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, largely paediatric.
Sources: Literature
Ataxia - adult onset v1.15 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, 617717 to Auditory neuropathy and optic atrophy, 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Ataxia - adult onset v1.14 FDXR Zornitza Stark Publications for gene: FDXR were set to
Ataxia - adult onset v1.13 FDXR Zornitza Stark Classified gene: FDXR as Amber List (moderate evidence)
Ataxia - adult onset v1.13 FDXR Zornitza Stark Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v1.12 FDXR Zornitza Stark changed review comment from: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; to: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, though largely paediatric.
Ataxia - adult onset v1.12 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals.; Changed rating: AMBER; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Regression v0.556 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Regression v0.555 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Regression v0.555 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Regression v0.554 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mitochondrial disease v0.927 FDXR Zornitza Stark Marked gene: FDXR as ready
Mitochondrial disease v0.927 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Mitochondrial disease v0.927 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mitochondrial disease v0.926 FDXR Zornitza Stark Publications for gene: FDXR were set to
Mitochondrial disease v0.925 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.924 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.923 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Leigh-like presentation at the severe end of the spectrum.; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.268 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, MIM# 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.267 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Microcephaly v1.266 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Microcephaly v1.266 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Microcephaly v1.265 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mendeliome v1.1879 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM#617717 to Auditory neuropathy and optic atrophy, MIM#617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Mendeliome v1.1878 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212; 28965846
Intellectual disability syndromic and non-syndromic v0.6061 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Mendeliome v1.1877 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM#617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Intellectual disability syndromic and non-syndromic v0.6060 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6059 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6057 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed rating: GREEN; Changed publications: 30250212, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887, Auditory neuropathy and optic atrophy, MIM# 617717
Prepair 1000+ v1.7 CLN5 Lauren Rogers reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, MIM# 256731, MONDO:0009745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD40 Lauren Rogers reviewed gene: CD40: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency with hyper-IgM, type 3, MIM# 606843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 CD3D Lauren Rogers reviewed gene: CD3D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 19, severe combined MIM# 615617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS12 Lauren Rogers reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 12, MIM# 615989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 BBS1 Lauren Rogers reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20177705, 15637713; Phenotypes: Bardet-Biedl syndrome 1, MIM# 209900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ATP6V1B1 Lauren Rogers reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM# 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ARL6 Lauren Rogers reviewed gene: ARL6: Rating: ; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481, 31736247, 19858128; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151; Mode of inheritance: None
Prepair 1000+ v1.7 ANTXR2 Lauren Rogers reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12973667, 14508707; Phenotypes: Hyaline fibromatosis syndrome, MIM# 228600, MONDO:0009229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALOX12B Lauren Rogers reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 11773004; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ADPRHL2 Karina Sandoval reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30100084, 30401461, 35664652; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (MIM#618170); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ALMS1 Lauren Rogers reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alstrom syndrome, MIM# 203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 AAAS Lauren Rogers reviewed gene: AAAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 29255950; Phenotypes: Achalasia-addisonianism-alacrimia syndrome, MIM#231550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ACAD9 Karina Sandoval reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30025539, 26475292; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 (MIM#611126); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.7 ABCA12 Karina Sandoval reviewed gene: ABCA12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31168818, 19664001, 31489029; Phenotypes: Ichthyosis, congenital, autosomal recessive 4A (MIM#601277), Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Marked gene: SLC25A32 as ready
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Classified gene: SLC25A32 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.6 SLC25A32 Bryony Thompson Gene: slc25a32 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.5 SLC25A32 Bryony Thompson gene: SLC25A32 was added
gene: SLC25A32 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 35727412; 34764427; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive MONDO:0014795
Review for gene: SLC25A32 was set to GREEN
Added comment: 5 cases with MADD from 4 unrelated families (4 homozygotes & 1 chet) and a supporting mouse model. At least 2 cases and the mouse model had exercise intolerance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6057 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Intellectual disability syndromic and non-syndromic v0.6056 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1877 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Mendeliome v1.1876 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Speech apraxia v1.0 Zornitza Stark promoted panel to version 1.0
Aminoacidopathy v1.66 SLC1A3 Sangavi Sivagnanasundram gene: SLC1A3 was added
gene: SLC1A3 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to 27829685, 16116111, 29062094, 19139306, 29208948, 29066757, 32754645, 25497598
Phenotypes for gene: SLC1A3 were set to episodic ataxia type 6 MONDO:0012982
Mode of pathogenicity for gene: SLC1A3 was set to Other
Review for gene: SLC1A3 was set to GREEN
Added comment: Variants reported in 8 unrelated probands with reported errors in glutamate metabolism. Mechanism of disease varies depending on the mutation. The most severe variants (p.M128R, p.P290R, and p.T318A) appear to have gain of function mechanism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 09/10/2020
https://search.clinicalgenome.org/CCID:006154
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A2 Sangavi Sivagnanasundram gene: SLC1A2 was added
gene: SLC1A2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to 23934111; 27476654; 28777935; 30937933
Phenotypes for gene: SLC1A2 were set to developmental and epileptic encephalopathy, 41 MONDO:0014916
Review for gene: SLC1A2 was set to GREEN
Added comment: Reported variants in 6 unrelated probands. The mechanism of disease is heterozygous dominant negative.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2020
https://search.clinicalgenome.org/CCID:006153
Sources: ClinGen
Aminoacidopathy v1.66 SLC1A1 Sangavi Sivagnanasundram gene: SLC1A1 was added
gene: SLC1A1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SLC1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A1 were set to 21123949
Phenotypes for gene: SLC1A1 were set to dicarboxylic aminoaciduria MONDO:0009110
Review for gene: SLC1A1 was set to AMBER
Added comment: Reported in 2 unrelated probands along with a mouse knockout model recapitulating human phenotype.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006152
Sources: ClinGen
Aminoacidopathy v1.66 SHMT2 Sangavi Sivagnanasundram gene: SHMT2 was added
gene: SHMT2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733; 35398349; 29323231
Phenotypes for gene: SHMT2 were set to neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities MONDO:0030866
Review for gene: SHMT2 was set to GREEN
Added comment: Reported in 5 unrelated probands with abnormal biochemical function.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006136
Sources: ClinGen
Mendeliome v1.1876 SELENBP1 Sangavi Sivagnanasundram gene: SELENBP1 was added
gene: SELENBP1 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: SELENBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SELENBP1 were set to 29255262
Phenotypes for gene: SELENBP1 were set to extraoral halitosis due to methanethiol oxidase deficiency MONDO:0029144
Review for gene: SELENBP1 was set to GREEN
Added comment: 3 unrelated probands in one publication. All reported individuals had a “cabbage-like” breath odour due to the elevated levels of methanethiol and dimethylsulfide in their breath.
Knockout mouse model recapitulating the human phenotype including the biochemical characteristics.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006103
Sources: ClinGen
Aminoacidopathy v1.66 SELENBP1 Sangavi Sivagnanasundram gene: SELENBP1 was added
gene: SELENBP1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SELENBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SELENBP1 were set to 29255262
Phenotypes for gene: SELENBP1 were set to extraoral halitosis due to methanethiol oxidase deficiency MONDO:0029144
Review for gene: SELENBP1 was set to GREEN
Added comment: 3 unrelated probands in one publication. All reported individuals had a “cabbage-like” breath odour due to the elevated levels of methanethiol and dimethylsulfide in their breath.
Knockout mouse model recapitulating the human phenotype including the biochemical characteristics.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 11/11/2022
https://search.clinicalgenome.org/CCID:006103
Sources: ClinGen
Aminoacidopathy v1.66 SARDH Sangavi Sivagnanasundram gene: SARDH was added
gene: SARDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: SARDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARDH were set to 22825317
Phenotypes for gene: SARDH were set to sarcosinemia MONDO:0010008
Review for gene: SARDH was set to RED
Added comment: The clinical phenotypes vary and sarcosinemia is considered a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:006052
Sources: ClinGen
Aminoacidopathy v1.66 QDPR Sangavi Sivagnanasundram gene: QDPR was added
gene: QDPR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to 14114862; 3033643; 11153907; 9341885; 19099731
Phenotypes for gene: QDPR were set to dihydropteridine reductase deficiency MONDO:0009862
Review for gene: QDPR was set to GREEN
Added comment: Well established gene disease association. LoF is a mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 18/06/2018
https://search.clinicalgenome.org/CCID:005939
Sources: ClinGen
Aminoacidopathy v1.66 PYCR1 Sangavi Sivagnanasundram gene: PYCR1 was added
gene: PYCR1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to 19576563; 19648921
Phenotypes for gene: PYCR1 were set to autosomal recessive cutis laxa type 2B MONDO:0013051
Review for gene: PYCR1 was set to GREEN
Added comment: Established gene disease association with reported individuals having an inborn error of proline metabolism.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 21/05/2020
https://search.clinicalgenome.org/CCID:005936
Sources: ClinGen
Aminoacidopathy v1.66 PTS Sangavi Sivagnanasundram gene: PTS was added
gene: PTS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTS were set to 22729819; 21542064; 20059486
Phenotypes for gene: PTS were set to BH4-deficient hyperphenylalaninemia A MONDO:0009863
Review for gene: PTS was set to GREEN
Added comment: Well established gene-disease association. >5 unrelated individuals reported with a biochemical phenotype. LoF is the mechanism of disease.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 22/12/2017
https://search.clinicalgenome.org/CCID:005931
Sources: ClinGen
Aminoacidopathy v1.66 PSPH Sangavi Sivagnanasundram gene: PSPH was added
gene: PSPH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSPH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSPH were set to 26589312, 25080166, 14673469; 27604308; 26888760; 25152457
Phenotypes for gene: PSPH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSPH was set to GREEN
Added comment: Established gene disease assocation. Reported in >5 unrelated individuals with biochemical phenotypes.
Classified as Moderate by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005917
Sources: ClinGen
Aminoacidopathy v1.66 PSAT1 Sangavi Sivagnanasundram gene: PSAT1 was added
gene: PSAT1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PSAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAT1 were set to 26610677; 12633500; 27626380; 32077105
Phenotypes for gene: PSAT1 were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PSAT1 was set to GREEN
Added comment: Well established gene disease association with reported individuals having errors in serine deficiency. Severity of the condition depends on the residual enzyme activity.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005912
Sources: ClinGen
Mendeliome v1.1876 PRODH2 Sangavi Sivagnanasundram gene: PRODH2 was added
gene: PRODH2 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: PRODH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH2 were set to 27139199
Phenotypes for gene: PRODH2 were set to hydroxyprolinemia MONDO:0009374
Review for gene: PRODH2 was set to RED
Added comment: PMID: 27139199
Variants reported in 6 individuals however only 2 cases presented with intermittant biochemical phenotype however the cause remains unclear. The rest of the individuals were asymptomatic suggesting that hydroxyprolinemia is a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005893
Sources: ClinGen
Aminoacidopathy v1.66 PRODH2 Sangavi Sivagnanasundram gene: PRODH2 was added
gene: PRODH2 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PRODH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH2 were set to 27139199
Phenotypes for gene: PRODH2 were set to hydroxyprolinemia MONDO:0009374
Review for gene: PRODH2 was set to RED
Added comment: PMID: 27139199
Variants reported in 6 individuals however only 2 cases presented with intermittant biochemical phenotype however the cause remains unclear. The rest of the individuals were asymptomatic suggesting that hydroxyprolinemia is a benign condition.

Classified as Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022
https://search.clinicalgenome.org/CCID:005893
Sources: ClinGen
Aminoacidopathy v1.66 PRODH Sangavi Sivagnanasundram gene: PRODH was added
gene: PRODH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PRODH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRODH were set to 12217952
Phenotypes for gene: PRODH were set to hyperprolinemia type 1 MONDO:0009400
Review for gene: PRODH was set to GREEN
Added comment: Well established gene disease association with reported individuals having an inborn error of proline metabolism.
Reported affected individuals have reported 2-10 times the normal plasma proline level.

Classified as Moderate by ClinGen Aminoacidopathy GCEP on 27/04/2021
https://search.clinicalgenome.org/CCID:005892
Sources: ClinGen
Aminoacidopathy v1.66 PHYKPL Sangavi Sivagnanasundram gene: PHYKPL was added
gene: PHYKPL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHYKPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHYKPL were set to 23242558
Phenotypes for gene: PHYKPL were set to phosphohydroxylysinuria MONDO:0014008
Review for gene: PHYKPL was set to RED
Added comment: Chet individual reported with variants in this gene and a phenotype similar to EDS. This individual was not reported to any metabolic phenotype. No other reports published at this stage to support gene-disease association.

Classified as Limitied by ClinGen Aminoacidopathy GCEP on 17/11/2023
https://search.clinicalgenome.org/CCID:005792
Sources: ClinGen
Aminoacidopathy v1.66 PHGDH Sangavi Sivagnanasundram gene: PHGDH was added
gene: PHGDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 37347880; 19235232; 24836451; 28440900; 22393170; 25913727
Phenotypes for gene: PHGDH were set to neurometabolic disorder due to serine deficiency MONDO:0018162
Review for gene: PHGDH was set to GREEN
Added comment: Established gene-disease association. >10 unrelated probands reported with an inborn error of serine deficiency. LoF is the mechanism of disease (PMID: 37347880).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020
https://search.clinicalgenome.org/CCID:005786
Sources: ClinGen
Aminoacidopathy v1.66 PCBD1 Sangavi Sivagnanasundram gene: PCBD1 was added
gene: PCBD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PCBD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCBD1 were set to 19234759
Phenotypes for gene: PCBD1 were set to pterin-4 alpha-carbinolamine dehydratase 1 deficiency MONDO:0009908
Review for gene: PCBD1 was set to GREEN
Added comment: Well established gene disease association with affected individuals having a transient hyperphenylalaninemia phenotype.

Mechanism of disease appears to be a defect in BH4 regeneration leading to an excess build up of phenylalanine and primapterim levels in blood, urine and tissues (PMID: 19234759)

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 27/07/2021
https://search.clinicalgenome.org/CCID:005739
Sources: ClinGen
Aminoacidopathy v1.66 PAH Sangavi Sivagnanasundram gene: PAH was added
gene: PAH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to 1301187, 13138177
Phenotypes for gene: PAH were set to phenylketonuria MONDO:0009861
Review for gene: PAH was set to GREEN
Added comment: Well-established gene-disease association. Affected individuals reported to have an inborn error of phenylalanine metabolism. LoF is the established mechanism of disease (PMID:1301187).

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 24/04/2020
https://search.clinicalgenome.org/CCID:005722
Sources: ClinGen
Aminoacidopathy v1.66 OTC Sangavi Sivagnanasundram gene: OTC was added
gene: OTC was added to Aminoacidopathy. Sources: Other
Mode of inheritance for gene: OTC 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: OTC were set to 26059767
Phenotypes for gene: OTC were set to ornithine carbamoyltransferase deficiency MONDO:0010703
Review for gene: OTC was set to GREEN
Added comment: Well established gene-disease association where affected individuals have a deficiency in carbamoyltransferase which affects the urea cycle.

Classified as Definitive by ClinGen Aminoacidopathy GCEP on 29/10/2019
https://search.clinicalgenome.org/CCID:005712
Sources: Other
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Marked gene: COPA as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.57 COPA Zornitza Stark Phenotypes for gene: COPA were changed from COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease to Autoimmune interstitial lung, joint, and kidney disease, MIM# 616414
Mendeliome v1.1876 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1876 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Mendeliome v1.1876 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1875 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.190 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.189 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Deafness_Isolated v1.63 GAS2 Zornitza Stark Marked gene: GAS2 as ready
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.63 GAS2 Zornitza Stark Classified gene: GAS2 as Amber List (moderate evidence)
Deafness_Isolated v1.63 GAS2 Zornitza Stark Gene: gas2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.62 GAS2 Zornitza Stark gene: GAS2 was added
gene: GAS2 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: GAS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAS2 were set to 33964205
Phenotypes for gene: GAS2 were set to Deafness, autosomal recessive 125, MIM#620877
Review for gene: GAS2 was set to AMBER
Added comment: Single family reported with four affected brothers and a splicing variant. Supportive mouse model.
Sources: Literature
Mendeliome v1.1874 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, MIM# 610357 to Neuropathy, hereditary sensory, type IIC, MIM# 614213; NESCAV syndrome, MIM# 614255; Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Mendeliome v1.1873 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Neuropathy, hereditary sensory, type IIC, MIM# 614213, NESCAV syndrome, MIM# 614255, Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - adult onset v1.11 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, autosomal recessive, 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - adult onset v1.10 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.76 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, MIM# 610357 to Spastic paraplegia 30, autosomal dominant MIM# 610357; Spastic paraplegia 30, autosomal recessive 620607
Hereditary Spastic Paraplegia - paediatric v1.75 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: Spastic paraplegia 30, autosomal dominant MIM# 610357, Spastic paraplegia 30, autosomal recessive 620607
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Classified gene: COPA as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.56 COPA Chirag Patel Gene: copa has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.55 COPA Chirag Patel gene: COPA was added
gene: COPA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: COPA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPA were set to PMID: 27048656, 30385646, 30804679, 29977900
Phenotypes for gene: COPA were set to COPA syndrome - autoimmune disorder associated with childhood interstitial lung disease and pulmonary haemorrhage, arthritis, and kidney disease
Review for gene: COPA was set to GREEN
gene: COPA was marked as current diagnostic
Added comment: Over 10 unrelated families reported.
Well-established gene-disease association.
Sources: Expert list
Ichthyosis v1.11 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.11 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Ichthyosis v1.11 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.10 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6055 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Mendeliome v1.1873 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1873 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1872 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Genetic Epilepsy v1.33 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Genetic Epilepsy v1.33 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.32 USP25 Zornitza Stark gene: USP25 was added
gene: USP25 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: USP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP25 were set to 38875478
Phenotypes for gene: USP25 were set to Epilepsy, idiopathic generalized, MONDO:0005579, USP25-related
Review for gene: USP25 was set to GREEN
Added comment: PMID: 38875478 5 heterozygous variants were identified in 8 individuals from 5 unrelated families all with clinical phenotypes associated with generalised epilepsy. Knock-out mouse model showed increased seizure susceptibility compared to the WT. Both loss of function and gain of function variants can be a mechanism of disease in individuals with USP25-related epilepsy.
Sources: Literature
Mendeliome v1.1871 USP25 Zornitza Stark Marked gene: USP25 as ready
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1871 USP25 Zornitza Stark Classified gene: USP25 as Green List (high evidence)
Mendeliome v1.1871 USP25 Zornitza Stark Gene: usp25 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1870 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Mendeliome v1.1870 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Classified gene: C10orf71 as Green List (high evidence)
Dilated Cardiomyopathy v1.31 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mendeliome v1.1869 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Mendeliome v1.1868 PSMC5 Zornitza Stark Publications for gene: PSMC5 were set to 33057194
Mendeliome v1.1867 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Mendeliome v1.1867 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6054 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Early-onset Parkinson disease v2.3 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.2 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Fetal anomalies v1.255 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.254 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Arthrogryposis v0.411 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.411 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Arthrogryposis v0.411 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Arthrogryposis v0.410 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Arthrogryposis. Sources: Expert list
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Expert list
Mendeliome v1.1866 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Mendeliome v1.1866 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Mendeliome v1.1866 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Mendeliome v1.1865 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6051 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Regression v0.554 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.554 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.553 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Regression v0.553 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Regression v0.552 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Regression v0.552 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Red List (Low Evidence).
Regression v0.552 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Regression. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex.

Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Severe Combined Immunodeficiency (absent T present B cells) v1.6 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Severe Combined Immunodeficiency (absent T present B cells) v1.5 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T present B cells) v1.4 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1864 POLD3 Zornitza Stark Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency MONDO:0015974 to Immunodeficiency 122, MIM# 620869
Mendeliome v1.1863 POLD3 Zornitza Stark Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Mendeliome v1.1862 POLD3 Zornitza Stark Classified gene: POLD3 as Green List (high evidence)
Mendeliome v1.1862 POLD3 Zornitza Stark Gene: pold3 has been classified as Green List (High Evidence).
Mendeliome v1.1861 POLD3 Zornitza Stark reviewed gene: POLD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38099988; Phenotypes: Immunodeficiency 122, MIM# 620869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.418 ALDH1A2 Gina Ravenscroft commented on gene: ALDH1A2
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Marked gene: SGK3 as ready
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson Gene: sgk3 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.24 SGK3 Bryony Thompson gene: SGK3 was added
gene: SGK3 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGK3 were set to 31821448; 21451460
Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets
Review for gene: SGK3 was set to RED
Added comment: SGK3 c.979-96T>A reported to segregate in the single family is more common in gnomAD v4.1 than expected for a dominant disease: global allele frequency of 0.004729 (0.5%, 5,882/1,243,870 alleles, 27 homozygotes in gnomAD v4.1).
A knockout mouse model had decreased bone density and increased phosphaturia.
Sources: Literature
Mendeliome v1.1861 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Mendeliome v1.1861 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Mendeliome v1.1860 TUBA4A Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38884572, 37418012; Phenotypes: Hereditary ataxia MONDO:0100309, TUBA4A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 25374358; 25893256; 28069311; 38463699; 38884572; 26675813
Motor Neurone Disease v1.23 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Motor Neurone Disease v1.22 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Added comment: At least 13 probands reported with ALS or phenotype including motor neurone involvement. Limited segregation evidence and mechanism of disease not established - toxic gain of function, dominant negative, or loss of function suggested
PMID: 25374358 - 7 rare TUBA4A variants OR = 36 [95% CI: 10–210], p = 4.3 × 10−7, Pcorrected = 4.2 × 10−3 in an FALS cohort. Included 1 nonsense (W407X in last exon) and 6 missense variants. FALS cases n=635, controls n=5,510. T145P variant segregated with disease within the family, while K430N was not detected in an affected first cousin of the sequenced proband (?phenocopy). Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability - suggesting a dominant negative mechanism of disease.
PMID: 25893256 - 4 Italian sporadic ALS cases with rare TUBA4A variants (3 missense & 1 splice variant). Minigene assay demonstrates c.226+4A>G causes exon 2 skipping which is expected to a frameshift and NMD. Loss of function is not an established mechanism of ALS in relation to TUBA4A.
PMID: 28069311 - rare missense (Thr381Met) detected in 2 siblings with ALS, but both had the C9orf72 expansion
PMID: 38463699 - reduced TUBA4A protein expression in familial and sporadic ALS brain tissue. Knockout zebrafish has a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype
PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Amyotrophy or upper limb muscular weakness in 2/12, 16.6%.; Changed rating: GREEN; Changed publications: 25374358, 25893256, 28069311, 38463699, 38884572; Changed phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.24 TUBA4A Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813
Early-onset Dementia v1.23 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed phenotypes: Inherited neurodegenerative disorder MONDO:0024237, TUBA4A-related
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Early-onset Dementia v1.23 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Early-onset Dementia v1.22 TUBA4A Bryony Thompson reviewed gene: TUBA4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25374358, 28069311, 35327632, 34169147, 38884572, 33760283; Phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.39 KAT6A Thomas Scerri changed review comment from: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.75 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.74 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v1.10 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.9 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Hereditary Spastic Paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - paediatric v1.24 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - paediatric v1.23 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Mode of pathogenicity for gene: TUBA4A was set to Other
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson edited their review of gene: TUBA4A: Changed mode of pathogenicity: Other
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Marked gene: TUBA4A as ready
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Classified gene: TUBA4A as Green List (high evidence)
Ataxia - adult onset v1.12 TUBA4A Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence).
Ataxia - adult onset v1.11 TUBA4A Bryony Thompson gene: TUBA4A was added
gene: TUBA4A was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 38884572; 37418012
Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related
Review for gene: TUBA4A was set to GREEN
Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease.

PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6050 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1860 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.253 VPS50 Ain Roesley Publications for gene: VPS50 were set to PMID: 34037727
Fetal anomalies v1.252 VPS50 Ain Roesley reviewed gene: VPS50: Rating: AMBER; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.31 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727; 38876772
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Genetic Epilepsy v1.30 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Genetic Epilepsy v1.30 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v1.29 VPS50 Ain Roesley commented on gene: VPS50: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Genetic Epilepsy v1.29 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cholestasis v0.240 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Microcephaly v1.265 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Mendeliome v1.1860 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Fetal anomalies v1.252 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Fetal anomalies v1.252 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Mendeliome v1.1860 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Mendeliome v1.1860 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Fetal anomalies v1.252 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Phenotypes for gene: SERPINA11 were set to pericardial effusion; pleural effusion
Review for gene: SERPINA11 was set to RED
gene: SERPINA11 was marked as current diagnostic
Added comment: 1 family with 2 fetuses.

1st fetus presented with isolated pericardial effusion and a TOP was opted.
post mortem:
mild subcutaneous edema with subtle facial dysmorphic features
small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces

2nd fetus also presented with pleural and pericardial effusion and a TOP was opted
post mortem findings were similar to fetus#1

homozygous nonsense variant in SERPINA11 was found p.(Tyr224*)

Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium
Sources: Literature
Mendeliome v1.1860 SERPINA11 Ain Roesley Phenotypes for gene: SERPINA11 were changed from to pericardial effusion; pleural effusion
Mendeliome v1.1859 SERPINA11 Ain Roesley edited their review of gene: SERPINA11: Changed phenotypes: pericardial effusion, pleural effusion
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1859 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Review for gene: SERPINA11 was set to RED
gene: SERPINA11 was marked as current diagnostic
Added comment: 1 family with 2 fetuses.

1st fetus presented with isolated pericardial effusion and a TOP was opted.
post mortem:
mild subcutaneous edema with subtle facial dysmorphic features
small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces

2nd fetus also presented with pleural and pericardial effusion and a TOP was opted
post mortem findings were similar to fetus#1

homozygous nonsense variant in SERPINA11 was found p.(Tyr224*)

Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6048 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD11 were set to 38866022; 30733659
Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related
Review for gene: PSMD11 was set to GREEN
Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease

PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11
Sources: Literature
Mendeliome v1.1858 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1858 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Mendeliome v1.1858 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Mendeliome v1.1857 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD11 were set to 38866022; 30733659
Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related
Review for gene: PSMD11 was set to GREEN
Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease

PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11
Sources: Literature
Microcephaly v1.265 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Microcephaly v1.265 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Cholestasis v0.240 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Cholestasis v0.240 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Mendeliome v1.1856 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Mendeliome v1.1856 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Microcephaly v1.264 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1855 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Cholestasis v0.239 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Cholestasis v0.239 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1855 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Marked gene: PAK2 as ready
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6046 PAK2 Ain Roesley gene: PAK2 was added
gene: PAK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784; 38894571; 38712026
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to GREEN
gene: PAK2 was marked as current diagnostic
Added comment: total of 3 families including 2 siblings with intra-familial variability

Siblings' phenotypes:
Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy.

Other 2 pro bands:
GDD, delayed motor (but normal verbal) skills, hypotonia

Missense variants with in vitro functional demonstrating reduction in PAK2 auto phosphorylation
Sources: Literature
Genetic Epilepsy v1.29 PAK2 Ain Roesley Publications for gene: PAK2 were set to 33693784
Genetic Epilepsy v1.29 PAK2 Ain Roesley Classified gene: PAK2 as Amber List (moderate evidence)
Genetic Epilepsy v1.29 PAK2 Ain Roesley Gene: pak2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.28 PAK2 Ain Roesley reviewed gene: PAK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38894571, 38712026; Phenotypes: Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Dilated Cardiomyopathy v1.30 C10orf71 Sangavi Sivagnanasundram gene: C10orf71 was added
gene: C10orf71 was added to Dilated Cardiomyopathy. Sources: Other
Mode of inheritance for gene: C10orf71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C10orf71 were set to 38950288
Phenotypes for gene: C10orf71 were set to dilated cardiomyopathy MONDO:0005021
Review for gene: C10orf71 was set to GREEN
Added comment: Identified a frameshift variant in a large multigenerational family with 8 affected individuals.
Further identified four other loss of function variants in a large Chinese cohort of sporadic DCM cases. >50 unrelated individuals identified with loss of function variants.

c10orf71-Knockout mouse model recapitulating DCM human phenotype (impairs cardiac function) in the presence of the frameshift variant.
Sources: Other
Mendeliome v1.1855 C10orf71 Sangavi Sivagnanasundram gene: C10orf71 was added
gene: C10orf71 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: C10orf71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C10orf71 were set to 38950288
Phenotypes for gene: C10orf71 were set to dilated cardiomyopathy MONDO:0005021
Review for gene: C10orf71 was set to GREEN
Added comment: Identified a frameshift variant in a large multigenerational family with 8 affected individuals.
Further identified four other loss of function variants in a large Chinese cohort of sporadic DCM cases. >50 unrelated individuals identified with loss of function variants.

c10orf71-Knockout mouse model recapitulating DCM human phenotype (impairs cardiac function) in the presence of the frameshift variant.
Sources: Other
Mendeliome v1.1855 PAK2 Ain Roesley Publications for gene: PAK2 were set to 33693784
Mendeliome v1.1854 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Mendeliome v1.1854 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Mendeliome v1.1853 PAK2 Ain Roesley reviewed gene: PAK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38894571, 38712026; Phenotypes: Knobloch syndrome 2 MIM#618458; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 500+ v1.1 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530 (3) to Intellectual developmental disorder, X-linked 1 MIM#309530
Prepair 1000+ v1.7 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530 (3) to Intellectual developmental disorder, X-linked 1 MIM#309530
Mendeliome v1.1853 USP25 Sangavi Sivagnanasundram gene: USP25 was added
gene: USP25 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: USP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP25 were set to 38875478
Phenotypes for gene: USP25 were set to USP25-related epilepsy (epilepsy, idiopathic generalized, MONDO:0005579)
Mode of pathogenicity for gene: USP25 was set to Other
Review for gene: USP25 was set to GREEN
Added comment: PMID: 38875478
5 heterozygous variants were identified in 8 individuals from 5 unrelated families all with clinical phenotypes associated with generalised epilepsy.

Knock-out mouse model showed increased seizure susceptibility compared to the WT.
Both loss of function and gain of function variants can be a mechanism of disease in individuals with USP25-related epilepsy.
Sources: Other
Mendeliome v1.1853 RTN2 Zornitza Stark Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; distal hereditary motor neuropathy, MONDO:0018894 to Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854
Hereditary Neuropathy_CMT - isolated v1.48 RTN2 Zornitza Stark Phenotypes for gene: RTN2 were changed from distal hereditary motor neuropathy, MONDO:0018894, RTN2-related to Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854
Hereditary Neuropathy_CMT - isolated v1.47 RTN2 Zornitza Stark edited their review of gene: RTN2: Changed phenotypes: Neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity, MIM# 620854
Speech apraxia v0.39 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Speech apraxia v0.38 FOXP2 Thomas Scerri changed review comment from: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Lai et al. (2001; PMID: 11586359) reported a 3-generation family with speech apraxia carrying a missense FOXP2 variant and also an independent case with a translocation affecting FOXP2.

Morison et al. (2023; PMID 36328423) "phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years)" and found "speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%)".
Speech apraxia v0.38 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ZBTB18 Thomas Scerri changed review comment from: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo ZBTB18 nonsense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 TAOK2 Thomas Scerri changed review comment from: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo TAOK2 missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 SPAST Thomas Scerri changed review comment from: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with an de novo SPAST missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 PURA Thomas Scerri changed review comment from: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.

Also several cases of "absence of speech" in the literature.

Sources: Expert list, Expert Review
Speech apraxia v0.38 PURA Thomas Scerri changed review comment from: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review
Speech apraxia v0.38 PHF21A Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo PHF21A frameshift variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 KDM5C Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.38 SHANK3 Thomas Scerri changed review comment from: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SHANK3 frameshift variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review
Speech apraxia v0.38 CHD3 Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.; to: First reported CAS case with a de novo CHD3 missense variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.
Speech apraxia v0.38 TNRC6B Thomas Scerri edited their review of gene: TNRC6B: Changed rating: RED
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a loss-of-function variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying loss-of-function variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 MKL2 Thomas Scerri edited their review of gene: MKL2: Changed rating: RED
Speech apraxia v0.38 GNAO1 Thomas Scerri edited their review of gene: GNAO1: Changed rating: RED
Speech apraxia v0.38 ERF Thomas Scerri edited their review of gene: ERF: Changed rating: RED
Speech apraxia v0.38 SHANK3 Thomas Scerri edited their review of gene: SHANK3: Changed rating: AMBER
Speech apraxia v0.38 ZNF142 Thomas Scerri changed review comment from: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.
Sources: Expert list, Expert Review; to: First reported CAS proband with compound heterozygous ZNF142 missenses variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous loss-of-function or missense ZNF142 variants for which the cases have a range of speech deficits, including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic loss-of-function ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.

Sources: Expert list, Expert Review
Speech apraxia v0.38 UPF2 Thomas Scerri changed review comment from: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo UPF2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with loss-of-function UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).

Sources: Expert list, Expert Review
Speech apraxia v0.38 POGZ Thomas Scerri changed review comment from: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo POGZ missense variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review
Speech apraxia v0.38 MEIS2 Thomas Scerri changed review comment from: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list; to: First reported CAS proband with a MEI2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list
Speech apraxia v0.38 GNB1 Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733).
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNB1 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Sources: Expert list, Expert Review
Speech apraxia v0.38 GNAO1 Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNAO1 missense variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases had "expressive speech disorder (3/3)" and one was reported with apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 EBF3 Thomas Scerri edited their review of gene: EBF3: Changed publications: 32345733, 28017372, 35340043
Speech apraxia v0.38 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.38 DDX3X Thomas Scerri changed review comment from: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733).

Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209)

Third in-house CAS proband with a de novo LoF DDX3X variant (not published).

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review; to: Hildebrand et al. (2020; PMID: 32345733) report the first CAS case has a de novo DDX3X frameshift variant.

Kaspi et al. (2022; PMID: 36117209) report a case with dysarthria and a de novo DDX3X nonsense variant.

An independent (unpublished) in-house CAS proband has a de novo DDX3X nonsense variant.

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%; 30/34)".
Sources: Expert list, Expert Review
Speech apraxia v0.38 CDK13 Thomas Scerri changed review comment from: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo CDK13 missense variant (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review
Speech apraxia v0.38 ERF Thomas Scerri changed review comment from: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (2022; PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ERF Thomas Scerri changed review comment from: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.38 DIP2C Thomas Scerri changed review comment from: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo DIP2C splice acceptor variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.38 BRPF1 Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo BRPF1 missense variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.38 ARHGEF9 Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo ARHGEF9 nonsense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 ZFHX4 Thomas Scerri changed review comment from: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review; to: First reported CAS case with a ZFHX4 splice acceptor variant (Eising et al., 2019; PMID: 29463886)

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Snijders Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri edited their review of gene: WDR5: Changed rating: AMBER
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia.

Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 WDR5 Thomas Scerri changed review comment from: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886)

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review
Speech apraxia v0.38 TNRC6B Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886)

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1B Thomas Scerri changed review comment from: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1B missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 SETBP1 Thomas Scerri changed review comment from: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review; to: First reported CAS case with a SETBP1 frameshift variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with loss-of-function SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%; 25/31) being the most common diagnosis.".
Sources: Expert list, Expert Review
Cerebral Palsy v1.356 ZDHHC9 Zornitza Stark Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Gene: zic2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Classified gene: ZIC2 as Red List (low evidence)
Cerebral Palsy v1.355 ZIC2 Zornitza Stark Gene: zic2 has been classified as Red List (Low Evidence).
Speech apraxia v0.38 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Speech apraxia v0.38 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Speech apraxia v0.38 ZBTB18 Zornitza Stark Classified gene: ZBTB18 as Red List (low evidence)
Speech apraxia v0.38 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Speech apraxia v0.37 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Speech apraxia v0.37 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Speech apraxia v0.37 TRIP12 Zornitza Stark Classified gene: TRIP12 as Red List (low evidence)
Speech apraxia v0.37 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Speech apraxia v0.36 TAOK2 Zornitza Stark Marked gene: TAOK2 as ready
Speech apraxia v0.36 TAOK2 Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence).
Speech apraxia v0.36 TAOK2 Zornitza Stark Classified gene: TAOK2 as Red List (low evidence)
Speech apraxia v0.36 TAOK2 Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence).
Speech apraxia v0.35 SPAST Zornitza Stark Marked gene: SPAST as ready
Speech apraxia v0.35 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Speech apraxia v0.35 SPAST Zornitza Stark Classified gene: SPAST as Red List (low evidence)
Speech apraxia v0.35 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Speech apraxia v0.34 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Speech apraxia v0.34 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Speech apraxia v0.34 SHANK3 Zornitza Stark Classified gene: SHANK3 as Green List (high evidence)
Speech apraxia v0.34 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Speech apraxia v0.33 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Speech apraxia v0.33 SETD1B Zornitza Stark Classified gene: SETD1B as Red List (low evidence)
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Mendeliome v1.1852 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Mendeliome v1.1852 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1852 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Mendeliome v1.1852 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1851 RBFOX3 Zornitza Stark gene: RBFOX3 was added
gene: RBFOX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908
Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related
Review for gene: RBFOX3 was set to AMBER
Added comment: Reported as a candidate gene for epilepsy, particularly Rolandic epilepsy. Two supportive animal models.
Sources: Literature
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Genetic Epilepsy v1.28 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.27 RBFOX3 Zornitza Stark gene: RBFOX3 was added
gene: RBFOX3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 35951651; 36117209; 24039908
Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related
Review for gene: RBFOX3 was set to AMBER
Added comment: Reported as a candidate gene for epilepsy, particularly Rolandic epilepsy. Two supportive animal models.
Sources: Literature
Speech apraxia v0.32 RBFOX3 Zornitza Stark Marked gene: RBFOX3 as ready
Speech apraxia v0.32 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.32 RBFOX3 Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence)
Speech apraxia v0.32 RBFOX3 Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1850 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Mendeliome v1.1849 GRXCR2 Zornitza Stark Mode of inheritance for gene: GRXCR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1848 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Mendeliome v1.1848 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
Mendeliome v1.1847 GRXCR2 Zornitza Stark edited their review of gene: GRXCR2: Added comment: PMID:33528103 reported another family and an unrelated individual from Cameroon with a different homozygous variant (c.251delC/ p.Ile85SerfsTer33).; Changed rating: GREEN; Changed publications: 24619944, 33528103
Deafness_Isolated v1.61 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Deafness_Isolated v1.60 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Deafness_Isolated v1.60 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
Deafness_Isolated v1.59 GRXCR2 Zornitza Stark reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528103; Phenotypes: Deafness, autosomal recessive 101, MIM# 615837; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.188 GRXCR2 Zornitza Stark Publications for gene: GRXCR2 were set to 24619944
Deafness_IsolatedAndComplex v1.187 GRXCR2 Zornitza Stark Classified gene: GRXCR2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.187 GRXCR2 Zornitza Stark Gene: grxcr2 has been classified as Green List (High Evidence).
Speech apraxia v0.31 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review; to: First reported CAS case with a MKL2 splice acceptor variant (Eising et al., 2019; PMID: 29463886). However, it is only predicted to be likely pathogenic and is observed 500+ times in gnomad v4 and has a low variant quality score.

Andrews et al. (2023; PMID: 37013900) identify two cases with de novo MKL2 missense variants (p.R104G and p.A91P) with reported gain of function. One case is reported with apraxia and the other with speech apraxia (Table 1).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.31 KAT6A Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Speech apraxia v0.31 KAT6A Thomas Scerri changed review comment from: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia.

St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. "


Sources: Expert list, Expert Review
Speech apraxia v0.31 CHD3 Thomas Scerri changed review comment from: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886).

Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia.

Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley Marked gene: YY1AP1 as ready
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley Gene: yy1ap1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley edited their review of gene: YY1AP1: Changed publications: 37979122, 33125268
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley gene: YY1AP1 was added
gene: YY1AP1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YY1AP1 were set to Grange syndrome, MIM# 602531
Review for gene: YY1AP1 was set to RED
gene: YY1AP1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 33125268 was cited in paper above.
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature
Cerebral Palsy v1.354 ZIC2 Clare van Eyk gene: ZIC2 was added
gene: ZIC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC2 were set to PMID: 38553553
Phenotypes for gene: ZIC2 were set to Holoprosencephaly, MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Spontaneous coronary artery dissection v0.31 PKD1 Ain Roesley Publications for gene: PKD1 were set to 35630097; 26798684; 26971055
Spontaneous coronary artery dissection v0.30 PKD1 Ain Roesley edited their review of gene: PKD1: Changed publications: 35630097, 26798684, 26971055, 29650765; Changed phenotypes: Polycystic kidney disease 1 MIM#173900
Spontaneous coronary artery dissection v0.30 PKD1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"


Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature

PMID: 29650765; reports 1x SCAD + ADPKD Individual with Cys37Tyr which is absent in gnomad and clinvar
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley Marked gene: TSR1 as ready
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley Gene: tsr1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley gene: TSR1 was added
gene: TSR1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TSR1 was set to Unknown
Publications for gene: TSR1 were set to PMID: 31296288; 31296287; 37979122
Review for gene: TSR1 was set to RED
gene: TSR1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 31296287 was cited by paper above.
SCAD cohort with WES performed and 'rare' variants filtered for. However, the variants have the following het counts in gnomad v4
Arg772Gln 27 hets 0 homs
Arg622Cys 45 hets 0 homs
Arg497Gln 7125 hets 33 homs
Trp556* absent
Arg499Pro absent
M1fs absent

PMID: 31296288 reviews PMID: 31296287

this gene is NOT constraint for LoF in gnomad v4 with 81 hets having an NMD nonsense hets
Sources: Literature
Cerebral Palsy v1.354 ZDHHC9 Clare van Eyk edited their review of gene: ZDHHC9: Added comment: Additional hemizygous male (maternally inherited) with splice variant described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed publications: PMID: 33528536, PMID: 38693247, PMID: 38553553
Speech apraxia v0.31 ZBTB18 Thomas Scerri gene: ZBTB18 was added
gene: ZBTB18 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to 36117209
Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM# 612337
Review for gene: ZBTB18 was set to RED
Added comment: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TRIP12 Thomas Scerri gene: TRIP12 was added
gene: TRIP12 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to 36117209
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM# 617752
Review for gene: TRIP12 was set to RED
Added comment: First reported CAS case with a de novo exon duplication of TRIP12 (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TAOK2 Thomas Scerri gene: TAOK2 was added
gene: TAOK2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK2 were set to 36117209
Phenotypes for gene: TAOK2 were set to Neurodevelopmental disorder (MONDO:0700092), TAOK2-related
Review for gene: TAOK2 was set to RED
Added comment: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SPAST Thomas Scerri gene: SPAST was added
gene: SPAST was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPAST were set to 36117209
Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant, MIM# 182601
Review for gene: SPAST was set to RED
Added comment: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SHANK3 Thomas Scerri gene: SHANK3 was added
gene: SHANK3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 36117209; 33293697
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232
Review for gene: SHANK3 was set to GREEN
Added comment: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review
Speech apraxia v0.31 SETD1B Thomas Scerri gene: SETD1B was added
gene: SETD1B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1B were set to 36117209
Phenotypes for gene: SETD1B were set to Intellectual developmental disorder with seizures and language delay, MIM# 619000
Review for gene: SETD1B was set to RED
Added comment: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 RBFOX3 Thomas Scerri gene: RBFOX3 was added
gene: RBFOX3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 36117209; 24039908
Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related
Review for gene: RBFOX3 was set to AMBER
Added comment: First reported CAS case with a paternally inherited nonsense RBFOX3 variant (Kaspi et al., 2022; PMID: 36117209). The carrier father was also affected.

Lal et al. (2013; PMID: 24039908) report two cases with nonsense RBFOX3 variants, both with initial speech or language delay, and one of which with "Moderate developmetal delay, delayed speech development, mild oral dyspraxia".
Sources: Expert list, Expert Review
Cerebral Palsy v1.354 PDE10A Zornitza Stark Marked gene: PDE10A as ready
Cerebral Palsy v1.354 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.354 PDE10A Zornitza Stark Classified gene: PDE10A as Red List (low evidence)
Cerebral Palsy v1.354 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.353 PHIP Zornitza Stark Classified gene: PHIP as Green List (high evidence)
Cerebral Palsy v1.353 PHIP Zornitza Stark Gene: phip has been classified as Green List (High Evidence).
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Marked gene: PHKA2 as ready
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Gene: phka2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Classified gene: PHKA2 as Red List (low evidence)
Cerebral Palsy v1.352 PHKA2 Zornitza Stark Gene: phka2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Classified gene: PIK3R2 as Amber List (moderate evidence)
Cerebral Palsy v1.351 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.350 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Cerebral Palsy v1.350 SOX2 Zornitza Stark Gene: sox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.350 SOX2 Zornitza Stark Classified gene: SOX2 as Red List (low evidence)
Cerebral Palsy v1.350 SOX2 Zornitza Stark Gene: sox2 has been classified as Red List (Low Evidence).
Speech apraxia v0.31 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Speech apraxia v0.31 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence).
Speech apraxia v0.31 HNRNPK Zornitza Stark Classified gene: HNRNPK as Red List (low evidence)
Speech apraxia v0.31 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence).
Speech apraxia v0.30 KDM5C Zornitza Stark Marked gene: KDM5C as ready
Speech apraxia v0.30 KDM5C Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence).
Speech apraxia v0.30 KDM5C Zornitza Stark Classified gene: KDM5C as Red List (low evidence)
Speech apraxia v0.30 KDM5C Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence).
Speech apraxia v0.29 PHF21A Zornitza Stark Marked gene: PHF21A as ready
Speech apraxia v0.29 PHF21A Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence).
Speech apraxia v0.29 PHF21A Zornitza Stark Classified gene: PHF21A as Red List (low evidence)
Speech apraxia v0.29 PHF21A Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence).
Speech apraxia v0.28 PURA Zornitza Stark Marked gene: PURA as ready
Speech apraxia v0.28 PURA Zornitza Stark Gene: pura has been classified as Red List (Low Evidence).
Speech apraxia v0.28 PURA Zornitza Stark Classified gene: PURA as Red List (low evidence)
Speech apraxia v0.28 PURA Zornitza Stark Gene: pura has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.93 ERG Zornitza Stark Classified gene: ERG as Green List (high evidence)
Bone Marrow Failure v1.93 ERG Zornitza Stark Gene: erg has been classified as Green List (High Evidence).
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Classified gene: TRIP12 as Red List (low evidence)
Cerebral Palsy v1.349 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.348 TRIP12 Clare van Eyk gene: TRIP12 was added
gene: TRIP12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to PMID: 36747006
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM#617752
Review for gene: TRIP12 was set to RED
Added comment: Single individual with de novo splice variant described in WGS study of clinically confirmed CP (PMID: 38553553). Motor delays are reported to be common in TRIP12 syndrome.
Sources: Literature
Bone Marrow Failure v1.92 ERG Hamish Scott reviewed gene: ERG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: cytopenia, Thrombocytopenia, MDS, Lymphedema; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Marked gene: TLN1 as ready
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Gene: tln1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Classified gene: TLN1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Gene: tln1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.28 TLN1 Ain Roesley gene: TLN1 was added
gene: TLN1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLN1 were set to 30888838; 37979122
Phenotypes for gene: TLN1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TLN1 was set to AMBER
gene: TLN1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature
Early-onset Dementia v1.22 GBA Lauren Rogers reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36084847; Phenotypes: {Lewy body dementia, susceptibility to} (MIM# 127750); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley Marked gene: PTGIR as ready
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley Gene: ptgir has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley gene: PTGIR was added
gene: PTGIR was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: PTGIR was set to Unknown
Publications for gene: PTGIR were set to 32531060; 37979122
Review for gene: PTGIR was set to RED
gene: PTGIR was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant
Sources: Literature
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley Marked gene: PKD1 as ready
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley Gene: pkd1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley gene: PKD1 was added
gene: PKD1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: PKD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PKD1 were set to 35630097; 26798684; 26971055
Phenotypes for gene: PKD1 were set to Polycystic kidney disease 1 MIM#173900
Review for gene: PKD1 was set to RED
gene: PKD1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"


Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley Marked gene: LMX1B as ready
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley Gene: lmx1b has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley gene: LMX1B was added
gene: LMX1B was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMX1B were set to 37979122; 29650765
Phenotypes for gene: LMX1B were set to Nail-patella syndrome MIM#161200
Review for gene: LMX1B was set to RED
gene: LMX1B was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs
Sources: Literature
Spontaneous coronary artery dissection v0.24 MYLK Ain Roesley Classified gene: MYLK as Green List (high evidence)
Spontaneous coronary artery dissection v0.24 MYLK Ain Roesley Gene: mylk has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.23 MYLK Ain Roesley gene: MYLK was added
gene: MYLK was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: MYLK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYLK were set to 30071989; 27586135; 21055718; 25907466
Phenotypes for gene: MYLK were set to Aortic aneurysm, familial thoracic 7 MIM#613780
Review for gene: MYLK was set to GREEN
gene: MYLK was marked as current diagnostic
Added comment: Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).

"Definitive" by Clingen Aortopathy Working Group.
Sources: Literature
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Marked gene: LOX as ready
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Gene: lox has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Classified gene: LOX as Green List (high evidence)
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Gene: lox has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.21 LOX Ain Roesley gene: LOX was added
gene: LOX was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LOX were set to 30071989; 26838787; 30675029.
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10 MIM#617168
Review for gene: LOX was set to GREEN
gene: LOX was marked as current diagnostic
Added comment: Reviewed as having 'strong' gene-disease association by the HTAAD working group, based on ClinGen framework (PMID: 30071989).

Missense and nonsense variants described in six unrelated families with HTAAD and functional studies of three missense variants demonstrated a reduction in LOX activity (Guo et.al. (2016); PMID: 26838787).

Two further individuals with negative family history: one individual has pathogenic nonsense variant and second individual has VUS missense variant (Renner et al. (2019); PMID: 30675029).
Sources: Literature
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Marked gene: FLNA as ready
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Gene: flna has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Classified gene: FLNA as Green List (high evidence)
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Gene: flna has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.19 FLNA Ain Roesley gene: FLNA was added
gene: FLNA was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: FLNA 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: FLNA were set to 29334594
Phenotypes for gene: FLNA were set to periventricular heterotopia 1 MIM#300049
Review for gene: FLNA was set to GREEN
gene: FLNA was marked as current diagnostic
Added comment: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).
Sources: Literature
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Marked gene: FBN1 as ready
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Gene: fbn1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Classified gene: FBN1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Gene: fbn1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.17 FBN1 Ain Roesley gene: FBN1 was added
gene: FBN1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 29357934
Phenotypes for gene: FBN1 were set to Marfan syndrome MIM#154700; familial thoracic aortic aneurysm and aortic dissection MONDO:0019625, FBN1-related
Review for gene: FBN1 was set to GREEN
gene: FBN1 was marked as current diagnostic
Added comment: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation
Sources: Literature
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Marked gene: COL5A1 as ready
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Gene: col5a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Classified gene: COL5A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Gene: col5a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.15 COL5A1 Ain Roesley gene: COL5A1 was added
gene: COL5A1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: COL5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL5A1 were set to 32938213
Phenotypes for gene: COL5A1 were set to Ehlers-Danlos syndrome, classic type, 1 MIM#130000; Fibromuscular dysplasia, multifocal MIM#619329
Review for gene: COL5A1 was set to GREEN
gene: COL5A1 was marked as current diagnostic
Added comment: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur.

4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available.
Sources: Literature
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Marked gene: COL3A1 as ready
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Gene: col3a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Classified gene: COL3A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Gene: col3a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.13 COL3A1 Ain Roesley gene: COL3A1 was added
gene: COL3A1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL3A1 were set to 30071989
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type MIM#130050
Review for gene: COL3A1 was set to GREEN
gene: COL3A1 was marked as current diagnostic
Added comment: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.
Sources: Literature
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Marked gene: TGFBR2 as ready
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Gene: tgfbr2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Classified gene: TGFBR2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Gene: tgfbr2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.11 TGFBR2 Ain Roesley gene: TGFBR2 was added
gene: TGFBR2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR2 were set to 30071989; 27879313
Phenotypes for gene: TGFBR2 were set to Loeys-Dietz syndrome 2 MIM#610168
Review for gene: TGFBR2 was set to GREEN
gene: TGFBR2 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (265 cases with variants in TGFBR2).
Sources: Literature
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Marked gene: TGFBR1 as ready
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Classified gene: TGFBR1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.9 TGFBR1 Ain Roesley gene: TGFBR1 was added
gene: TGFBR1 was added to Spontaneous coronary artery dissection. Sources: Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR1 were set to 36584339; 30071989; 27879313
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome 1 MIM#609192
Review for gene: TGFBR1 was set to GREEN
gene: TGFBR1 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).

AMBER for AR disease: PMID 36584339
Biallelic variants reported in a single family with two sibs. Presented with severe dilatation of aorta, diaphragmatic hernia, skin translucency, and profound joint laxity at birth
Sources: Radboud University Medical Center, Nijmegen
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Marked gene: TGFB3 as ready
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Gene: tgfb3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Classified gene: TGFB3 as Green List (high evidence)
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Gene: tgfb3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.7 TGFB3 Ain Roesley gene: TGFB3 was added
gene: TGFB3 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFB3 were set to 30071989; 25835445
Phenotypes for gene: TGFB3 were set to Loeys-Dietz syndrome 5 MIM#615582
Review for gene: TGFB3 was set to GREEN
gene: TGFB3 was marked as current diagnostic
Added comment: Uncertain for isolated aneurysm, but causes broader connective tissue disorder phenotype. 43 patients from 11 reported with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlapped clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity
Sources: Literature
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Marked gene: TGFB2 as ready
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Gene: tgfb2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Classified gene: TGFB2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Gene: tgfb2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.5 TGFB2 Ain Roesley gene: TGFB2 was added
gene: TGFB2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFB2 were set to 30071989; 22772371
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4 MIM#614816
Penetrance for gene: TGFB2 were set to Complete
Review for gene: TGFB2 was set to GREEN
gene: TGFB2 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy Working Group.

PMID: 22772371: 4 families
Sources: Literature
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Marked gene: SMAD3 as ready
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Gene: smad3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Classified gene: SMAD3 as Green List (high evidence)
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Gene: smad3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.3 SMAD3 Ain Roesley gene: SMAD3 was added
gene: SMAD3 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD3 were set to 21217753; 30661052; 30071989
Phenotypes for gene: SMAD3 were set to Loeys-Dietz syndrome 3, MIM# 613795
Review for gene: SMAD3 was set to GREEN
gene: SMAD3 was marked as current diagnostic
Added comment: Missense variants within the MH2 domain have been suggested to exert dominant negative mechanism by disprupting the formation of homo-oligomers (PMID: 30661052) Loss-of-function proven for PTCs (PMID: 30661052)

"Definitive" by ClinGen Aortopathy working group.
Sources: Literature
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Marked gene: SMAD2 as ready
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Gene: smad2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Classified gene: SMAD2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Gene: smad2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.1 SMAD2 Ain Roesley gene: SMAD2 was added
gene: SMAD2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD2 were set to 29967133
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, MIM# 619656
Penetrance for gene: SMAD2 were set to Complete
Review for gene: SMAD2 was set to GREEN
gene: SMAD2 was marked as current diagnostic
Added comment: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Sources: Literature
Spontaneous coronary artery dissection v0.0 Ain Roesley Added Panel Spontaneous coronary artery dissection
Set panel types to: Victorian Clinical Genetics Services
Speech apraxia v0.27 PURA Thomas Scerri edited their review of gene: PURA: Changed rating: RED
Speech apraxia v0.27 PURA Thomas Scerri gene: PURA was added
gene: PURA was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to 36117209
Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties, MIM# 616158
Added comment: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review
Speech apraxia v0.27 PHF21A Thomas Scerri gene: PHF21A was added
gene: PHF21A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF21A were set to 36117209
Phenotypes for gene: PHF21A were set to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725
Review for gene: PHF21A was set to RED
Added comment: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.27 KDM5C Thomas Scerri gene: KDM5C was added
gene: KDM5C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KDM5C 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: KDM5C were set to 36117209; 36434256
Phenotypes for gene: KDM5C were set to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, MIM# 300534
Review for gene: KDM5C was set to RED
Added comment: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.27 HNRNPK Thomas Scerri gene: HNRNPK was added
gene: HNRNPK was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 36117209
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome, MIM# 616580
Review for gene: HNRNPK was set to RED
Added comment: First reported CAS case with a de novo nonsense HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Cerebral Palsy v1.348 SOX2 Clare van Eyk gene: SOX2 was added
gene: SOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 38553553
Phenotypes for gene: SOX2 were set to Microphthalmia, syndromic 3; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM#206900
Review for gene: SOX2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553). SOX2 disorders are associated with a spectrum of phenotypes which frequently include psychomotor delay, hypotonia, dystonia (including status dystonicus), spastic diplegia/quadriplegia.
Sources: Literature
Cerebral Palsy v1.348 PIK3R2 Clare van Eyk gene: PIK3R2 was added
gene: PIK3R2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIK3R2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R2 were set to PMID: 38553553
Phenotypes for gene: PIK3R2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM#603387
Mode of pathogenicity for gene: PIK3R2 was set to Other
Review for gene: PIK3R2 was set to AMBER
Added comment: Single individual with de novo heterozygous p.G373R variant described in WGS study of clinically confirmed CP (PMID: 38553553). This variant is reported multiple times in ClinVar and literature as a recurrent pathogenic activating mutation. Additional case in literature with same variant and spastic hemiplegia (PMID: 26860062). Constitutional and mosaic mutations in PIK3R2 are associated with a range of developmental brain disorders.
Sources: Literature
Cerebral Palsy v1.348 PHKA2 Clare van Eyk gene: PHKA2 was added
gene: PHKA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHKA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PHKA2 were set to PMID: 38553553
Phenotypes for gene: PHKA2 were set to Glycogen storage disease, type IXa, 306000
Review for gene: PHKA2 was set to RED
Added comment: Single individual with de novo hemizygous variant described in WGS study of clinically confirmed CP (PMID: 38553553). Variant has multiple entries in ClinVar - pathogenic/likely pathogenic. GSD9A is primarily associated with liver dysfunction, however dysregulation of glucose metabolism can cause damage to the CNS.
Sources: Literature
Cerebral Palsy v1.348 PHIP Clare van Eyk edited their review of gene: PHIP: Added comment: Additional individual with a pathogenic de novo frameshift insertion described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed rating: GREEN; Changed publications: PMID: 38693247, PMID:33528536, PMID: 38553553
Cerebral Palsy v1.348 PDE10A Clare van Eyk gene: PDE10A was added
gene: PDE10A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDE10A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PDE10A were set to PMID: 38553553
Phenotypes for gene: PDE10A were set to Dyskinesia, limb and orofacial, infantile-onset, autosomal recessive, MIM#616921; Striatal degeneration, autosomal dominant, MIM#616922
Review for gene: PDE10A was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).

Biallelic variants have been reported to cause a hyperkinetic movement disorder with onset in infancy (PMID: 27058446).
Sources: Literature
Cerebral Palsy v1.348 MEF2C Clare van Eyk reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38553553; Phenotypes: Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.348 KDM3B Clare van Eyk gene: KDM3B was added
gene: KDM3B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to PMID: 38553553
Phenotypes for gene: KDM3B were set to Diets-Jongmans syndrome, MIM#618846
Review for gene: KDM3B was set to RED
Added comment: Single individual with de novo likely pathogenic variant described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Cerebral Palsy v1.348 GATAD2B Clare van Eyk edited their review of gene: GATAD2B: Added comment: Additional case with de novo heterozygous LP variant described in WGS study of clinically confirmed CP (PMID: 38553553). Same variant previously reported pathogenic from clinical testing in ClinVar, but no phenotypic data.; Changed publications: PMID: 38693247, PMID: 38553553
Cerebral Palsy v1.348 ERLIN2 Clare van Eyk gene: ERLIN2 was added
gene: ERLIN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ERLIN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERLIN2 were set to PMID: 38553553
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18A, autosomal dominant, MIM#620512; Spastic paraplegia 18B, autosomal recessive, MIM#611225
Review for gene: ERLIN2 was set to RED
Added comment: Single individual with homozygous frameshift insertion in ERLIN2 described in WGS study of clinically confirmed CP (PMID: 38553553). Both monoallelic and biallelic variants have been reported to cause hereditary spastic paraplegia.
Sources: Literature
Mendeliome v1.1847 THBS2 Zornitza Stark Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related to Ehlers-Danlos syndrome, classic type, 3, MIM# 620865
Aortopathy_Connective Tissue Disorders v1.85 THBS2 Zornitza Stark Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to Ehlers-Danlos syndrome, classic type, 3, MIM# 620865
Aortopathy_Connective Tissue Disorders v1.84 THBS2 Zornitza Stark reviewed gene: THBS2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, classic type, 3, MIM# 620865; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.186 GRXCR2 Achchuthan Shanmugasundram reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528103; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Classified gene: LZTR1 as Red List (low evidence)
Cerebral Palsy v1.348 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Classified gene: MCCC2 as Amber List (moderate evidence)
Cerebral Palsy v1.347 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.346 MED12 Zornitza Stark Marked gene: MED12 as ready
Cerebral Palsy v1.346 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.346 MED12 Zornitza Stark Publications for gene: MED12 were set to PMID: 38693247
Cerebral Palsy v1.345 MED12 Zornitza Stark Classified gene: MED12 as Amber List (moderate evidence)
Cerebral Palsy v1.345 MED12 Zornitza Stark Gene: med12 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.344 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Cerebral Palsy v1.344 MMACHC Zornitza Stark Gene: mmachc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.344 MMACHC Zornitza Stark Classified gene: MMACHC as Amber List (moderate evidence)
Cerebral Palsy v1.344 MMACHC Zornitza Stark Gene: mmachc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.343 MUT Zornitza Stark Marked gene: MUT as ready
Cerebral Palsy v1.343 MUT Zornitza Stark Gene: mut has been classified as Red List (Low Evidence).
Cerebral Palsy v1.343 MUT Zornitza Stark Classified gene: MUT as Red List (low evidence)
Cerebral Palsy v1.343 MUT Zornitza Stark Gene: mut has been classified as Red List (Low Evidence).
Cerebral Palsy v1.342 MYO9A Zornitza Stark Marked gene: MYO9A as ready
Cerebral Palsy v1.342 MYO9A Zornitza Stark Gene: myo9a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.342 MYO9A Zornitza Stark Classified gene: MYO9A as Red List (low evidence)
Cerebral Palsy v1.342 MYO9A Zornitza Stark Gene: myo9a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.341 PCLO Zornitza Stark Marked gene: PCLO as ready
Cerebral Palsy v1.341 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Cerebral Palsy v1.341 PCLO Zornitza Stark Classified gene: PCLO as Red List (low evidence)
Cerebral Palsy v1.341 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Marked gene: PIDD1 as ready
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Classified gene: PIDD1 as Red List (low evidence)
Cerebral Palsy v1.340 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.339 LRP2 Zornitza Stark Marked gene: LRP2 as ready
Cerebral Palsy v1.339 LRP2 Zornitza Stark Gene: lrp2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.339 LRP2 Zornitza Stark Classified gene: LRP2 as Red List (low evidence)
Cerebral Palsy v1.339 LRP2 Zornitza Stark Gene: lrp2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Marked gene: LAMA1 as ready
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Gene: lama1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Classified gene: LAMA1 as Red List (low evidence)
Cerebral Palsy v1.338 LAMA1 Zornitza Stark Gene: lama1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Marked gene: HCFC1 as ready
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Classified gene: HCFC1 as Amber List (moderate evidence)
Cerebral Palsy v1.337 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.336 FGD1 Zornitza Stark Marked gene: FGD1 as ready
Cerebral Palsy v1.336 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.336 FGD1 Zornitza Stark Classified gene: FGD1 as Red List (low evidence)
Cerebral Palsy v1.336 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.335 EBP Zornitza Stark Marked gene: EBP as ready
Cerebral Palsy v1.335 EBP Zornitza Stark Gene: ebp has been classified as Red List (Low Evidence).
Cerebral Palsy v1.335 EBP Zornitza Stark Classified gene: EBP as Red List (low evidence)
Cerebral Palsy v1.335 EBP Zornitza Stark Gene: ebp has been classified as Red List (Low Evidence).
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Classified gene: CCDC22 as Red List (low evidence)
Cerebral Palsy v1.334 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Speech apraxia v0.27 ERF Zornitza Stark Marked gene: ERF as ready
Speech apraxia v0.27 ERF Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.27 ERF Zornitza Stark Classified gene: ERF as Amber List (moderate evidence)
Speech apraxia v0.27 ERF Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.26 ZNF142 Zornitza Stark Marked gene: ZNF142 as ready
Speech apraxia v0.26 ZNF142 Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.26 ZNF142 Zornitza Stark Classified gene: ZNF142 as Amber List (moderate evidence)
Speech apraxia v0.26 ZNF142 Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.25 ZFHX4 Zornitza Stark Marked gene: ZFHX4 as ready
Speech apraxia v0.25 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence).
Speech apraxia v0.25 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Red List (low evidence)
Speech apraxia v0.25 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence).
Speech apraxia v0.24 WDR5 Zornitza Stark Marked gene: WDR5 as ready
Speech apraxia v0.24 WDR5 Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence).
Speech apraxia v0.24 WDR5 Zornitza Stark Classified gene: WDR5 as Green List (high evidence)
Speech apraxia v0.24 WDR5 Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence).
Speech apraxia v0.23 UPF2 Zornitza Stark Marked gene: UPF2 as ready
Speech apraxia v0.23 UPF2 Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence).
Speech apraxia v0.23 UPF2 Zornitza Stark Classified gene: UPF2 as Red List (low evidence)
Speech apraxia v0.23 UPF2 Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence).
Speech apraxia v0.22 TNRC6B Zornitza Stark Marked gene: TNRC6B as ready
Speech apraxia v0.22 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.22 TNRC6B Zornitza Stark Classified gene: TNRC6B as Amber List (moderate evidence)
Speech apraxia v0.22 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.21 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.21 SETD1A Zornitza Stark Classified gene: SETD1A as Amber List (moderate evidence)
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Classified gene: SETBP1 as Green List (high evidence)
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.19 POGZ Zornitza Stark Marked gene: POGZ as ready
Speech apraxia v0.19 POGZ Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence).
Speech apraxia v0.19 POGZ Zornitza Stark Classified gene: POGZ as Red List (low evidence)
Speech apraxia v0.19 POGZ Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence).
Speech apraxia v0.18 MEIS2 Zornitza Stark Marked gene: MEIS2 as ready
Speech apraxia v0.18 MEIS2 Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.18 MEIS2 Zornitza Stark Classified gene: MEIS2 as Amber List (moderate evidence)
Speech apraxia v0.18 MEIS2 Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.17 GNB1 Zornitza Stark Marked gene: GNB1 as ready
Speech apraxia v0.17 GNB1 Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence).
Speech apraxia v0.17 GNB1 Zornitza Stark Classified gene: GNB1 as Red List (low evidence)
Speech apraxia v0.17 GNB1 Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence).
Speech apraxia v0.16 GNAO1 Zornitza Stark Marked gene: GNAO1 as ready
Speech apraxia v0.16 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.16 GNAO1 Zornitza Stark Classified gene: GNAO1 as Amber List (moderate evidence)
Speech apraxia v0.16 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.15 EBF3 Zornitza Stark Marked gene: EBF3 as ready
Speech apraxia v0.15 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Speech apraxia v0.15 EBF3 Zornitza Stark Classified gene: EBF3 as Green List (high evidence)
Speech apraxia v0.15 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Speech apraxia v0.14 DIP2C Zornitza Stark Marked gene: DIP2C as ready
Speech apraxia v0.14 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Speech apraxia v0.14 DIP2C Zornitza Stark Classified gene: DIP2C as Green List (high evidence)
Speech apraxia v0.14 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Speech apraxia v0.13 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Speech apraxia v0.13 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Speech apraxia v0.13 DDX3X Zornitza Stark Classified gene: DDX3X as Green List (high evidence)
Speech apraxia v0.13 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Speech apraxia v0.12 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Speech apraxia v0.12 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Speech apraxia v0.12 CDK13 Zornitza Stark Classified gene: CDK13 as Green List (high evidence)
Speech apraxia v0.12 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Speech apraxia v0.11 BRPF1 Zornitza Stark Marked gene: BRPF1 as ready
Speech apraxia v0.11 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Speech apraxia v0.11 BRPF1 Zornitza Stark Classified gene: BRPF1 as Green List (high evidence)
Speech apraxia v0.11 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Speech apraxia v0.9 ARHGEF9 Zornitza Stark Classified gene: ARHGEF9 as Red List (low evidence)
Speech apraxia v0.9 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Classified gene: OPHN1 as Red List (low evidence)
Cerebral Palsy v1.333 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.332 PIGA Zornitza Stark Publications for gene: PIGA were set to 33528536; 24706016
Cerebral Palsy v1.331 PLP1 Zornitza Stark Publications for gene: PLP1 were set to 33528536; 25280894; 34816117
Cerebral Palsy v1.330 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Cerebral Palsy v1.330 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.330 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
Cerebral Palsy v1.330 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.329 POLA1 Zornitza Stark Marked gene: POLA1 as ready
Cerebral Palsy v1.329 POLA1 Zornitza Stark Gene: pola1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.329 POLA1 Zornitza Stark Classified gene: POLA1 as Amber List (moderate evidence)
Cerebral Palsy v1.329 POLA1 Zornitza Stark Gene: pola1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Classified gene: PQBP1 as Red List (low evidence)
Cerebral Palsy v1.328 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.327 TAF1 Zornitza Stark Publications for gene: TAF1 were set to 26637982; 33528536; 17273961
Cerebral Palsy v1.326 THOC2 Zornitza Stark Marked gene: THOC2 as ready
Cerebral Palsy v1.326 THOC2 Zornitza Stark Added comment: Comment when marking as ready: Amber rating due to lack of phenotypic data in the large cohort study.
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.326 THOC2 Zornitza Stark Classified gene: THOC2 as Amber List (moderate evidence)
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Classified gene: ZDHHC9 as Amber List (moderate evidence)
Cerebral Palsy v1.325 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.324 B4GALNT1 Zornitza Stark Classified gene: B4GALNT1 as Amber List (moderate evidence)
Cerebral Palsy v1.324 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.323 RARB Zornitza Stark Marked gene: RARB as ready
Cerebral Palsy v1.323 RARB Zornitza Stark Gene: rarb has been classified as Red List (Low Evidence).
Cerebral Palsy v1.323 RARB Zornitza Stark Classified gene: RARB as Red List (low evidence)
Cerebral Palsy v1.323 RARB Zornitza Stark Gene: rarb has been classified as Red List (Low Evidence).
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Cerebral Palsy v1.322 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.321 POLR2A Zornitza Stark Marked gene: POLR2A as ready
Cerebral Palsy v1.321 POLR2A Zornitza Stark Gene: polr2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.321 POLR2A Zornitza Stark Classified gene: POLR2A as Red List (low evidence)
Cerebral Palsy v1.321 POLR2A Zornitza Stark Gene: polr2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.320 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to 33528536; 34788679
Cerebral Palsy v1.319 KCNB1 Zornitza Stark Classified gene: KCNB1 as Green List (high evidence)
Cerebral Palsy v1.319 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.318 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Cerebral Palsy v1.318 CHD3 Zornitza Stark Gene: chd3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.318 CHD3 Zornitza Stark Classified gene: CHD3 as Red List (low evidence)
Cerebral Palsy v1.318 CHD3 Zornitza Stark Gene: chd3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Classified gene: ABHD16A as Red List (low evidence)
Cerebral Palsy v1.317 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Red List (low evidence)
Cerebral Palsy v1.316 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Red List (Low Evidence).
Mendeliome v1.1846 ERBB4 Zornitza Stark changed review comment from: ALS: at least 4 families reported with SNVs.

ID: intragenic deletions in 3 families, some inherited.; to: ALS: at least 4 families reported with SNVs, but LIMITED by ClinGen.

ID: intragenic deletions in 3 families, some inherited. Unclear if SNVs cause phenotype.
Mendeliome v1.1846 ERBB4 Zornitza Stark edited their review of gene: ERBB4: Changed rating: AMBER
Cerebral Palsy v1.315 ZMYM2 Clare van Eyk gene: ZMYM2 was added
gene: ZMYM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to PMID: 38168508
Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM#619522
Review for gene: ZMYM2 was set to RED
Added comment: Single case with de novo pathogenic variant in ZMYM2, diagnosed with spastic quadriplegic cerebral palsy originally attributed to other causes (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 ABHD16A Clare van Eyk gene: ABHD16A was added
gene: ABHD16A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 38168508
Phenotypes for gene: ABHD16A were set to Spastic paraplegia 86, autosomal recessive, MIM#619735
Review for gene: ABHD16A was set to RED
Added comment: Single case with homozygous LP variant in ABHD16A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508). SPG86 is associated with global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies.
Sources: Literature
Cerebral Palsy v1.315 CHD3 Clare van Eyk gene: CHD3 was added
gene: CHD3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 38168508
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to RED
Added comment: Single case with de novo LP variant in CHD3, diagnosed with spastic hemiplegic cerebral palsy with unclear cause (PMID: 38168508). Causal link not established.
Sources: Literature
Cerebral Palsy v1.315 KCNB1 Clare van Eyk edited their review of gene: KCNB1: Added comment: Additional case with de novo likely pathogenic variant, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: GREEN; Changed publications: PMID: 38693247, 38168508
Cerebral Palsy v1.315 POLR2A Clare van Eyk gene: POLR2A was added
gene: POLR2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to PMID: 38168508
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM#618603
Review for gene: POLR2A was set to RED
Added comment: Single case with de novo LP variant in POLR2A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 MAPK8IP3 Clare van Eyk gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to PMID: 38168508
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities, MIM#618443
Review for gene: MAPK8IP3 was set to AMBER
Added comment: Single case with pathogenic MAPK8IP3 variant, inheritance not confirmed, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).

Additional cases series reported two recurrent de novo missense variants in MAPK8IP3 in 5 individuals from four families with a core set of neurodevelopmental symptoms, including spastic diplegia, intellectual disability, and corpus callosum hypoplasia (PMID: 30945334).
Sources: Literature
Cerebral Palsy v1.315 RARB Clare van Eyk gene: RARB was added
gene: RARB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RARB were set to PMID: 38168508
Phenotypes for gene: RARB were set to Microphthalmia, syndromic 12, MIM#615524
Mode of pathogenicity for gene: RARB was set to Other
Review for gene: RARB was set to RED
Added comment: 1 individual reported with phenotype mimicking CP and recurrent p.Leu213Pro GOF variant in RARB. GOF variants in RARB are associated with severe global developmental delay with progressive motor impairment due to spasticity and/or dystonia (with or without chorea). Biallelic truncating variants also reported to cause microphthalmia and diaphragmatic hernia.
Sources: Literature
Cerebral Palsy v1.315 B4GALNT1 Clare van Eyk edited their review of gene: B4GALNT1: Added comment: Additional case with compound heterozygous variants in B4GALNT1, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: AMBER; Changed publications: PMID: 38693247, PMID: 38168508
Cerebral Palsy v1.315 ZDHHC9 Clare van Eyk gene: ZDHHC9 was added
gene: ZDHHC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: ZDHHC9 were set to Intellectual developmental disorder, X-linked syndromic, Raymond type, MIM#300799
Review for gene: ZDHHC9 was set to AMBER
Added comment: Single males hemizygous for P/LP variants reported in each of 2 large CP sequencing studies (PMID: 33528536; PMID: 38693247). Detailed clinical information not supplied for either. Genome-wide significant burden of rare variants in ZDHHC9 reported in panel resequencing study of CP cohort (PMID: 31700678).
Sources: Literature
Cerebral Palsy v1.315 THOC2 Clare van Eyk gene: THOC2 was added
gene: THOC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: THOC2 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: THOC2 were set to PMID: 38168508; PMID: 38693247; PMID: 32116545
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12, MIM#300957
Review for gene: THOC2 was set to GREEN
Added comment: 3 hemizygous males with pathogenic/likely pathogenic variants reported in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional female with cryptogenic spastic quadriplegic CP also reported with heterozygous de novo pathogenic THOC2 variant (PMID: 38168508). Some females reported in literature previously. Dyskinesia, dystonia and spasticity are reported as clinical features in several additional cases in a series (PMID: 32116545).
Sources: Literature
Cerebral Palsy v1.315 TAF1 Clare van Eyk reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966, Dystonia-Parkinsonism, X-linked, OMIM #314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 PQBP1 Clare van Eyk gene: PQBP1 was added
gene: PQBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PQBP1 were set to PMID: 38693247
Phenotypes for gene: PQBP1 were set to Renpenning syndrome, MIM#309500
Review for gene: PQBP1 was set to RED
Added comment: 1 hemizygous male reported with splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spastic diplegia is a common feature in individuals with Renpenning syndrome.
Sources: Literature
Cerebral Palsy v1.315 POLA1 Clare van Eyk gene: POLA1 was added
gene: POLA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLA1 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: POLA1 were set to PMID: 38693247
Phenotypes for gene: POLA1 were set to Van Esch-O'Driscoll syndrome, MIM#301030
Review for gene: POLA1 was set to AMBER
Added comment: 3 males with hemizygous LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spasticity has been reported as a rare feature of VEODS.
Sources: Literature
Cerebral Palsy v1.315 PHF6 Clare van Eyk gene: PHF6 was added
gene: PHF6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHF6 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: PHF6 were set to PMID: 38693247
Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome, MIM#301900
Review for gene: PHF6 was set to RED
Added comment: Single male proband with hemizygous variant impacting splicing of the first non-coding exon reported in large-scale exome sequencing study (PMID: 38693247). In silico prediction is strong, but functional impact not assessed. Detailed clinical information not supplied. BFLS is characterized by short stature, obesity, hypogonadism, hypotonia, intellectual disability, distinctive facial features, fleshy ears, and finger and toe abnormalities.
Sources: Literature
Cerebral Palsy v1.315 PLP1 Clare van Eyk reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 PIGA Clare van Eyk reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072, Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 OPHN1 Clare van Eyk gene: OPHN1 was added
gene: OPHN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPHN1 were set to PMID: 38693247
Phenotypes for gene: OPHN1 were set to Intellectual developmental disorder, X-linked syndromic, Billuart type, MIM#300486
Review for gene: OPHN1 was set to RED
Added comment: 1 male with hemizygous variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MRXSBL is associated with generalized hypotonia and delayed psychomotor development from infancy, with some individuals developing ataxia associated with cerebellar hypoplasia.
Sources: Literature
Speech apraxia v0.8 ERF Thomas Scerri gene: ERF was added
gene: ERF was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERF were set to 36117209; 35761471; 35852485
Phenotypes for gene: ERF were set to Craniosynostosis 4, MIM# 600775
Review for gene: ERF was set to AMBER
Added comment: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DIP2C Thomas Scerri gene: DIP2C was added
gene: DIP2C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to 36117209; 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO:0700092), DIP2C-related
Review for gene: DIP2C was set to AMBER
Added comment: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 BRPF1 Thomas Scerri gene: BRPF1 was added
gene: BRPF1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRPF1 were set to 36117209; 27939640; 38346666
Phenotypes for gene: BRPF1 were set to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333
Review for gene: BRPF1 was set to GREEN
Added comment: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 ARHGEF9 Thomas Scerri gene: ARHGEF9 was added
gene: ARHGEF9 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ARHGEF9 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: ARHGEF9 were set to 36117209
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM# 300607
Review for gene: ARHGEF9 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZNF142 Thomas Scerri gene: ZNF142 was added
gene: ZNF142 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF142 were set to 32345733; 31036918; 34531528; 35616059
Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM# 618425
Review for gene: ZNF142 was set to AMBER
Added comment: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.
Sources: Expert list, Expert Review
Speech apraxia v0.8 UPF2 Thomas Scerri gene: UPF2 was added
gene: UPF2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: UPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF2 were set to 32345733; 31585809
Phenotypes for gene: UPF2 were set to Neurodevelopmental disorder (MONDO:0700092), UPF2-related
Review for gene: UPF2 was set to RED
Added comment: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).
Sources: Expert list, Expert Review
Speech apraxia v0.8 POGZ Thomas Scerri gene: POGZ was added
gene: POGZ was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 32345733; 35052493
Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364
Review for gene: POGZ was set to RED
Added comment: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review
Speech apraxia v0.8 MEIS2 Thomas Scerri gene: MEIS2 was added
gene: MEIS2 was added to Speech apraxia. Sources: Expert Review,Expert list
Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEIS2 were set to 32345733; 30055086
Phenotypes for gene: MEIS2 were set to Cleft palate, cardiac defects, and impaired intellectual development, MIM# 600987
Review for gene: MEIS2 was set to AMBER
Added comment: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list
Speech apraxia v0.8 GNB1 Thomas Scerri gene: GNB1 was added
gene: GNB1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 32345733
Phenotypes for gene: GNB1 were set to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973
Review for gene: GNB1 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733).
Sources: Expert list, Expert Review
Speech apraxia v0.8 GNAO1 Thomas Scerri gene: GNAO1 was added
gene: GNAO1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAO1 were set to 32345733; 35722775; 38881224
Phenotypes for gene: GNAO1 were set to Developmental and epileptic encephalopathy 17, MIM# 615473; Neurodevelopmental disorder with involuntary movements, MIM# 617493
Review for gene: GNAO1 was set to AMBER
Added comment: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review
Speech apraxia v0.8 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.8 EBF3 Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.
Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.

Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables).

Sources: Expert list, Expert Review
Speech apraxia v0.8 DDX3X Thomas Scerri changed review comment from: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209)

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733).

Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209)

Third in-house CAS proband with a de novo LoF DDX3X variant (not published).

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 TNRC6B Thomas Scerri edited their review of gene: TNRC6B: Changed rating: AMBER
Speech apraxia v0.8 TNRC6B Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review; to: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

These additional supporting studies are for speech delay rather than speech apraxia per se:

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536); to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo likely pathogenic heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Cerebral Palsy v1.315 MED12 Clare van Eyk reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: Opitz-Kaveggia syndrome, MIM#305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 MED12 Clare van Eyk Deleted their review
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature; to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Sources: Literature
Cerebral Palsy v1.315 MED12 Clare van Eyk gene: MED12 was added
gene: MED12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MED12 were set to PMID: 38693247
Phenotypes for gene: MED12 were set to Opitz-Kaveggia syndrome, MIM#305450
Review for gene: MED12 was set to RED
Added comment: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature
Cerebral Palsy v1.315 L1CAM Clare van Eyk reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 KDM5C Clare van Eyk reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 HPRT1 Clare van Eyk reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hyperuricemia, HRPT-related MIM#300323, Lesch-Nyhan syndrome MIM#300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 HCFC1 Clare van Eyk gene: HCFC1 was added
gene: HCFC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to PMID: 38693247
Phenotypes for gene: HCFC1 were set to Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541
Review for gene: HCFC1 was set to AMBER
Added comment: 2 males reported with hemizygous LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MAHCX is characterized by severely delayed psychomotor development apparent in infancy.
Sources: Literature
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: AMBER
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: RED
Speech apraxia v0.8 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review; to: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Cerebral Palsy v1.315 CCDC22 Clare van Eyk changed review comment from: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature; to: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in CCDC22 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Cerebral Palsy v1.315 FGD1 Clare van Eyk gene: FGD1 was added
gene: FGD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGD1 were set to PMID: 38693247; PMID:33528536
Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome; Intellectual developmental disorder, X-linked syndromic 16, MIM#305400
Review for gene: FGD1 was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional male with de novo hemizygous pathogenic variant reported in a clinical laboratory referral cohort (PMID:33528536). No clear phenotypic overlap with CP.
Sources: Literature
Cerebral Palsy v1.315 EBP Clare van Eyk gene: EBP was added
gene: EBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EBP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EBP were set to PMID: 38693247
Phenotypes for gene: EBP were set to MEND syndrome, MIM#300960
Review for gene: EBP was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MEND syndrome is associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia).
Sources: Literature
Speech apraxia v0.8 EBF3 Thomas Scerri gene: EBF3 was added
gene: EBF3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to 32345733; 28017372
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Review for gene: EBF3 was set to GREEN
Added comment: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DDX3X Thomas Scerri gene: DDX3X was added
gene: DDX3X was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DDX3X 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: DDX3X were set to 32345733; 36117209; 37904618
Phenotypes for gene: DDX3X were set to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, MIM# 300958
Review for gene: DDX3X was set to GREEN
Added comment: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209)

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 CLCN4 Clare van Eyk reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37789889; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 CCDC22 Clare van Eyk gene: CCDC22 was added
gene: CCDC22 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CCDC22 were set to PMID: 38693247
Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2, MIM#300963
Review for gene: CCDC22 was set to RED
Added comment: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Microcephaly v1.264 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Deafness_IsolatedAndComplex v1.186 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Microcephaly v1.263 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Intellectual disability syndromic and non-syndromic v0.6045 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Congenital nystagmus v1.21 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Intellectual disability syndromic and non-syndromic v0.6044 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Mendeliome v1.1846 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Congenital nystagmus v1.20 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Deafness_IsolatedAndComplex v1.185 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Microcephaly v1.262 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Mendeliome v1.1845 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Ataxia - paediatric v1.22 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia - adult onset v1.10 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1844 MTCL1 Zornitza Stark Mode of inheritance for gene: MTCL1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6043 ZNF292 Ain Roesley Phenotypes for gene: ZNF292 were changed from Intellectual developmental disorder, autosomal dominant 63, MIM# 619188; Intellectual disability; autism; ADHD to Intellectual developmental disorder, autosomal dominant 64 MIM#619188
Mendeliome v1.1843 ZNF292 Ain Roesley Phenotypes for gene: ZNF292 were changed from Intellectual developmental disorder, autosomal dominant 63, MIM# 619188; Intellectual disability; Autism; ADHD to Intellectual developmental disorder, autosomal dominant 64 MIM#619188
Speech apraxia v0.8 CDK13 Thomas Scerri gene: CDK13 was added
gene: CDK13 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to 32345733; 36599938
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360
Review for gene: CDK13 was set to GREEN
Added comment: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZFHX4 Thomas Scerri gene: ZFHX4 was added
gene: ZFHX4 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 29463886; 34461323
Phenotypes for gene: ZFHX4 were set to Neurodevelopmental disorder (MONDO:0700092), ZFHX4-related
Review for gene: ZFHX4 was set to RED
Added comment: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review
Speech apraxia v0.8 WDR5 Thomas Scerri gene: WDR5 was added
gene: WDR5 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to 29463886; 36408368
Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder (MONDO:0700092), WDR5-related
Review for gene: WDR5 was set to GREEN
Added comment: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review
Speech apraxia v0.8 TNRC6B Thomas Scerri gene: TNRC6B was added
gene: TNRC6B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TNRC6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNRC6B were set to 29463886; 32152250; 38300321; 38404251
Phenotypes for gene: TNRC6B were set to Global developmental delay with speech and behavioral abnormalities, MIM# 619243
Review for gene: TNRC6B was set to GREEN
Added comment: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETD1A Thomas Scerri gene: SETD1A was added
gene: SETD1A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 29463886; 32346159
Phenotypes for gene: SETD1A were set to Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Review for gene: SETD1A was set to GREEN
Added comment: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETBP1 Thomas Scerri gene: SETBP1 was added
gene: SETBP1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETBP1 were set to 29463886; 33907317
Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM# 616078
Review for gene: SETBP1 was set to GREEN
Added comment: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review
Cerebral Palsy v1.315 ROGDI Zornitza Stark Marked gene: ROGDI as ready
Cerebral Palsy v1.315 ROGDI Zornitza Stark Gene: rogdi has been classified as Red List (Low Evidence).
Cerebral Palsy v1.315 ROGDI Zornitza Stark Classified gene: ROGDI as Red List (low evidence)
Cerebral Palsy v1.315 ROGDI Zornitza Stark Gene: rogdi has been classified as Red List (Low Evidence).
Cerebral Palsy v1.314 RTTN Zornitza Stark Marked gene: RTTN as ready
Cerebral Palsy v1.314 RTTN Zornitza Stark Gene: rttn has been classified as Red List (Low Evidence).
Cerebral Palsy v1.314 RTTN Zornitza Stark Classified gene: RTTN as Red List (low evidence)
Cerebral Palsy v1.314 RTTN Zornitza Stark Gene: rttn has been classified as Red List (Low Evidence).
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Marked gene: SLC25A12 as ready
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Classified gene: SLC25A12 as Red List (low evidence)
Cerebral Palsy v1.313 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.312 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Cerebral Palsy v1.311 SYNE1 Zornitza Stark Publications for gene: SYNE1 were set to 34321325; 34816117
Cerebral Palsy v1.310 TH Zornitza Stark Publications for gene: TH were set to 34788679
Cerebral Palsy v1.309 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Cerebral Palsy v1.309 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Cerebral Palsy v1.308 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Cerebral Palsy v1.308 VPS13B Zornitza Stark Gene: vps13b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.308 VPS13B Zornitza Stark Classified gene: VPS13B as Red List (low evidence)
Cerebral Palsy v1.308 VPS13B Zornitza Stark Gene: vps13b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.307 VPS53 Zornitza Stark Marked gene: VPS53 as ready
Cerebral Palsy v1.307 VPS53 Zornitza Stark Gene: vps53 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.307 VPS53 Zornitza Stark Classified gene: VPS53 as Red List (low evidence)
Cerebral Palsy v1.307 VPS53 Zornitza Stark Gene: vps53 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.306 WDR62 Zornitza Stark Marked gene: WDR62 as ready
Cerebral Palsy v1.306 WDR62 Zornitza Stark Gene: wdr62 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.306 WDR62 Zornitza Stark Classified gene: WDR62 as Red List (low evidence)
Cerebral Palsy v1.306 WDR62 Zornitza Stark Gene: wdr62 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.305 CDKL5 Zornitza Stark Publications for gene: CDKL5 were set to 33528536; 34788679
Cerebral Palsy v1.304 HUWE1 Zornitza Stark Publications for gene: HUWE1 were set to 31700678
Cerebral Palsy v1.303 HUWE1 Zornitza Stark Classified gene: HUWE1 as Amber List (moderate evidence)
Cerebral Palsy v1.303 HUWE1 Zornitza Stark Gene: huwe1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.302 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder MIM#309530
Cerebral Palsy v1.301 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175; 33528536
Cerebral Palsy v1.300 MECP2 Zornitza Stark Publications for gene: MECP2 were set to 30542205; 33528536
Cerebral Palsy v1.299 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to 33528536; 10486093
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Marked gene: SLC35A2 as ready
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Classified gene: SLC35A2 as Red List (low evidence)
Cerebral Palsy v1.298 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.297 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Cerebral Palsy v1.297 SMC1A Zornitza Stark Gene: smc1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.297 SMC1A Zornitza Stark Classified gene: SMC1A as Red List (low evidence)
Cerebral Palsy v1.297 SMC1A Zornitza Stark Gene: smc1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Classified gene: ABCD1 as Red List (low evidence)
Cerebral Palsy v1.296 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Marked gene: ARHGEF9 as ready
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Classified gene: ARHGEF9 as Red List (low evidence)
Cerebral Palsy v1.295 ARHGEF9 Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.294 ARHGEF9 Clare van Eyk gene: ARHGEF9 was added
gene: ARHGEF9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARHGEF9 were set to PMID: 38693247
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM#300607
Review for gene: ARHGEF9 was set to RED
Added comment: 1 individual reported with hemizygous pathogenic variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Impaired psychomotor development is a feature of DEE8.
Sources: Literature
Cerebral Palsy v1.294 ABCD1 Clare van Eyk gene: ABCD1 was added
gene: ABCD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCD1 were set to PMID: 38693247
Phenotypes for gene: ABCD1 were set to Adrenoleukodystrophy, MIM#300100
Review for gene: ABCD1 was set to RED
Added comment: 1 male with hemizygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Variable age of onset, even within same family. Heterozygous females may develop spastic paraparesis with bowel and bladder difficulties.
Sources: Literature
Cerebral Palsy v1.294 SMC1A Clare van Eyk gene: SMC1A was added
gene: SMC1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SMC1A were set to PMID: 38693247; 26358754
Phenotypes for gene: SMC1A were set to Developmental and epileptic encephalopathy 85, with or without midline brain defects, MIM#301044
Review for gene: SMC1A was set to RED
Added comment: 1 male reported with apparently hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). LOF variants thought to be male-lethal. Detailed clinical information not supplied.

1 female in literature with a heterozygous de novo splice site mutation in SMC1A and severe encephalopathy with early-onset epilepsy who developed spastic tetraparesis (PMID: 26358754)
Sources: Literature
Cerebral Palsy v1.294 SLC35A2 Clare van Eyk gene: SLC35A2 was added
gene: SLC35A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC35A2 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: SLC35A2 were set to PMID: 38693247
Phenotypes for gene: SLC35A2 were set to Congenital disorder of glycosylation, type IIm, MIM#300896
Review for gene: SLC35A2 was set to RED
Added comment: 1 individual reported with hemizygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variants cause an epileptic encephalopathy which has been associated with ataxia and hypotonia.
Sources: Literature
Cerebral Palsy v1.294 PDHA1 Clare van Eyk reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 PCDH19 Clare van Eyk changed review comment from: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 PCDH19 Clare van Eyk commented on gene: PCDH19: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 MECP2 Clare van Eyk reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Encephalopathy, neonatal severe - 300673, Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260, Intellectual developmental disorder, X-linked, syndromic 13 - 300055, Rett syndrome - 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 IQSEC2 Clare van Eyk reviewed gene: IQSEC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder MIM#309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 HUWE1 Clare van Eyk reviewed gene: HUWE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 CDKL5 Clare van Eyk reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 2, MIM#300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 WDR62 Clare van Eyk gene: WDR62 was added
gene: WDR62 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR62 were set to PMID: 38693247
Phenotypes for gene: WDR62 were set to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM#604317
Review for gene: WDR62 was set to RED
Added comment: 1 individual reported with biallelic pathogenic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

MCPH2 is associated with primary microcephaly with variable other neurodevelopmental features. Spastic quadriplegia, hemiplegia, hypertonia are reported.
Sources: Literature
Cerebral Palsy v1.294 VPS53 Clare van Eyk gene: VPS53 was added
gene: VPS53 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS53 were set to PMID: 38693247
Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, MIM#615851
Review for gene: VPS53 was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound intellectual disability, progressive microcephaly, spasticity, and early-onset epilepsy. 1 family reported with complex hereditary spastic paraparesis phenotype (PMID: 31418091).
Sources: Literature
Cerebral Palsy v1.294 VPS13B Clare van Eyk gene: VPS13B was added
gene: VPS13B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13B were set to PMID: 38693247
Phenotypes for gene: VPS13B were set to Cohen syndrome, MIM#216550
Review for gene: VPS13B was set to RED
Added comment: 2 individuals with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.294 TH Clare van Eyk reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 28904579; Phenotypes: Segawa syndrome, recessive, MIM#605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SYNE1 Clare van Eyk reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 30275942; Phenotypes: Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SLC25A12 Clare van Eyk gene: SLC25A12 was added
gene: SLC25A12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC25A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A12 were set to PMID: 31403263; PMID: 38693247
Phenotypes for gene: SLC25A12 were set to Developmental and epileptic encephalopathy 39, MIM#612949
Review for gene: SLC25A12 was set to RED
Added comment: 1 patient with novel compound heterozygous variants reported with spastic quadriplegic cerebral palsy (PMID: 31403263). Additional individual reported with homozygous missense variant in large-scale exome sequencing study (PMID: 38693247), however detailed clinical information and functional support for pathogenicity were not supplied.
Sources: Literature
Cerebral Palsy v1.294 RTTN Clare van Eyk gene: RTTN was added
gene: RTTN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RTTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTTN were set to PMID: 38693247
Phenotypes for gene: RTTN were set to Microcephaly, short stature, and polymicrogyria with seizures, MIM#614833
Review for gene: RTTN was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia and spasticity have been reported in MSSP.
Sources: Literature
Cerebral Palsy v1.294 ROGDI Clare van Eyk gene: ROGDI was added
gene: ROGDI was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ROGDI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROGDI were set to PMID: 38693247
Phenotypes for gene: ROGDI were set to Kohlschutter-Tonz syndrome, MIM#226750
Review for gene: ROGDI was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants (1 stopgain,1 splice) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Kohlschutter-Tonz syndrome is characterized by a consistent phenotype of severe global developmental delay, early-onset intractable seizures, progressive spasticity, and amelogenesis imperfecta causing discoloration of both primary and secondary teeth.
Sources: Literature
Speech apraxia v0.8 MKL2 Zornitza Stark changed review comment from: Only two individuals reported.; to: Only two individuals reported with GoF variants.

The variant reported in a third individual in PMID 29463886 is present in >500 individuals in gnomAD v4, and is marked as LCLoF.
Speech apraxia v0.8 MKL2 Zornitza Stark edited their review of gene: MKL2: Changed publications: 29463886
Speech apraxia v0.8 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Speech apraxia v0.8 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Speech apraxia v0.8 CHD3 Zornitza Stark Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome MIM#618205
Speech apraxia v0.7 CHD3 Zornitza Stark Classified gene: CHD3 as Green List (high evidence)
Speech apraxia v0.7 CHD3 Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence).
Speech apraxia v0.6 CHD3 Zornitza Stark reviewed gene: CHD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30397230; Phenotypes: Snijders Blok-Campeau syndrome MIM#618205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.6 KAT6A Zornitza Stark Marked gene: KAT6A as ready
Speech apraxia v0.6 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Speech apraxia v0.6 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from Childhood apraxia of speech; see comments. to Arboleda-Tham syndrome, MIM# 616268
Speech apraxia v0.5 KAT6A Zornitza Stark Classified gene: KAT6A as Green List (high evidence)
Speech apraxia v0.5 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Speech apraxia v0.4 KAT6A Zornitza Stark reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35892268; Phenotypes: Arboleda-Tham syndrome, MIM# 616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.4 MKL2 Zornitza Stark Marked gene: MKL2 as ready
Speech apraxia v0.4 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.4 MKL2 Zornitza Stark Phenotypes for gene: MKL2 were changed from Childhood apraxia of speech; see comments. to Neurodevelopmental disorder (MONDO:0700092), MKL2-related
Speech apraxia v0.3 MKL2 Zornitza Stark Classified gene: MKL2 as Amber List (moderate evidence)
Speech apraxia v0.3 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.2 MKL2 Zornitza Stark reviewed gene: MKL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MKL2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Speech apraxia v0.2 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Speech apraxia v0.2 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence).
Speech apraxia v0.2 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from Childhood apraxia of speech to Speech-language disorder-1, MIM# 602081
Speech apraxia v0.1 FOXP2 Zornitza Stark Classified gene: FOXP2 as Green List (high evidence)
Speech apraxia v0.1 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence).
Speech apraxia v0.0 FOXP2 Zornitza Stark reviewed gene: FOXP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.294 PIGN Zornitza Stark Publications for gene: PIGN were set to PMID: 33528536
Cerebral Palsy v1.293 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679
Cerebral Palsy v1.292 POLG Zornitza Stark Marked gene: POLG as ready
Cerebral Palsy v1.292 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.292 POLG Zornitza Stark Classified gene: POLG as Amber List (moderate evidence)
Cerebral Palsy v1.292 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.251 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies; Bilateral ventriculomegaly; aqueductal stenosis; Microcephaly; Hip dysplasia to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Intellectual disability syndromic and non-syndromic v0.6042 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Microcephaly v1.261 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Mendeliome v1.1842 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Cerebral Palsy v1.291 POLG Clare van Eyk gene: POLG was added
gene: POLG was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a, MIM#203700, Mitochondrial DNA Depletion Syndrome 4B, MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), MIM#607459
Review for gene: POLG was set to AMBER
Added comment: 1 individual reported with biallelic P/LP missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional individual reported in clinical referral cohort (PMID: 33528536). Mutations in POLG are associated with a wide range of clinical features including lactic acidosis, seizures, ataxia, peripheral neuropathy, developmental delay, myopathy, chronic progressive external ophthalmoplegia, and hepatopathy.
Sources: Literature
Cerebral Palsy v1.291 PLA2G6 Clare van Eyk reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 PIGN Clare van Eyk edited their review of gene: PIGN: Added comment: An additional individual reported with biallelic stopgain variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; Changed publications: PMID: 33528536, PMID: 34540776, PMID: 38693247
Cerebral Palsy v1.291 PIDD1 Clare van Eyk gene: PIDD1 was added
gene: PIDD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to PMID: 38693247
Phenotypes for gene: PIDD1 were set to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM#619827
Review for gene: PIDD1 was set to RED
Added comment: 1 individual reported with biallelic LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. PIDD1 is associated with an intellectual developmental disorder with variant lissencephaly.
Sources: Literature
Aminoacidopathy v1.66 OAT Sangavi Sivagnanasundram gene: OAT was added
gene: OAT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAT were set to 609808; 23076989; 24429551; 25264521
Phenotypes for gene: OAT were set to ornithine aminotransferase deficiency MONDO:0009796
Review for gene: OAT was set to GREEN
Added comment: Established gene disease association with mouse model recapitulating human phenotype.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 10/07/2019 - https://search.clinicalgenome.org/CCID:005692
Sources: ClinGen
Aminoacidopathy v1.66 NAT8L Sangavi Sivagnanasundram gene: NAT8L was added
gene: NAT8L was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 19807691
Phenotypes for gene: NAT8L were set to N-acetylaspartate deficiency MONDO:0013549
Review for gene: NAT8L was set to RED
Added comment: Reported in one individual with N-acetylaspartate deficiency but also has other severe neurological features however the gene-disease association in this individual is unclear.

Classified LIMITED by ClinGen Aminoacidopathy GCEP on 29/03/2024 - https://search.clinicalgenome.org/CCID:005565
Sources: ClinGen
Aminoacidopathy v1.66 NAGS Sangavi Sivagnanasundram gene: NAGS was added
gene: NAGS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: NAGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAGS were set to 15714518; 27037498; 22503289
Phenotypes for gene: NAGS were set to hyperammonemia due to N-acetylglutamate synthase deficiency MONDO:0009377
Review for gene: NAGS was set to GREEN
Added comment: Established gene-disease with reported individuals having an urea cycle disorder.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 26/07/2019 - https://search.clinicalgenome.org/CCID:005562
Sources: ClinGen
Aminoacidopathy v1.66 MTRR Sangavi Sivagnanasundram gene: MTRR was added
gene: MTRR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTRR were set to 10484769; 12555939; 15714522; 17369066
Phenotypes for gene: MTRR were set to methylcobalamin deficiency type cblE MONDO:0009354
Review for gene: MTRR was set to GREEN
Added comment: Well established gene-disease association with reported individuals having errors in cobalamin metabolism.

Classified DEFINITIVE by ClinGen Aminoacidopathy GCEP on 02/7/2021 - https://search.clinicalgenome.org/CCID:005505
Sources: ClinGen
Aminoacidopathy v1.66 MTR Sangavi Sivagnanasundram gene: MTR was added
gene: MTR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTR were set to 12068375; 30651581; 31951343
Phenotypes for gene: MTR were set to methylcobalamin deficiency type cblG MONDO:0009609
Review for gene: MTR was set to GREEN
Added comment: Well established gene-disease association with reported individuals having a deficiency methionine synthase.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 02/7/2021 - https://search.clinicalgenome.org/CCID:005503
Sources: ClinGen
Fetal anomalies v1.250 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1841 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.66 MTHFR Sangavi Sivagnanasundram gene: MTHFR was added
gene: MTHFR was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFR were set to 26872964
Phenotypes for gene: MTHFR were set to homocystinuria due to methylene tetrahydrofolate reductase deficiency MONDO:0009353
Review for gene: MTHFR was set to GREEN
Added comment: Established gene-disease association with reported individuals having reported elevated homocysteine and decreased methionine.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 18/06/2019 - https://search.clinicalgenome.org/CCID:005497
Sources: ClinGen
Aminoacidopathy v1.66 MPST Sangavi Sivagnanasundram gene: MPST was added
gene: MPST was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MPST was set to Unknown
Phenotypes for gene: MPST were set to encephalopathy due to beta-mercaptolactate-cysteine disulfiduria MONDO:0009585
Review for gene: MPST was set to RED
Added comment: No reported individuals with deficiency in MPST enzymatic activity.

No known disease relationship classification given by ClinGen Aminoacidopathy GCEP on
28/04/2023 - https://search.clinicalgenome.org/CCID:005413
Sources: ClinGen
Aminoacidopathy v1.66 MMACHC Sangavi Sivagnanasundram gene: MMACHC was added
gene: MMACHC was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 26149271; 28693988; 18164228; 16963011; 30157807; 16311595; 23580368
Phenotypes for gene: MMACHC were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Review for gene: MMACHC was set to GREEN
Added comment: Well established gene disease association with reported individuals having errors in biochemical function.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:005397
Sources: ClinGen
Aminoacidopathy v1.66 MCEE Sangavi Sivagnanasundram gene: MCEE was added
gene: MCEE was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MCEE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCEE were set to 16697227; 17823972; 27699154; 29104221; 30682498; 31146325
Phenotypes for gene: MCEE were set to methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency MONDO:0009615
Review for gene: MCEE was set to GREEN
Added comment: Established gene-disease association with >10 probands reported with variants in this gene.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 09/07/2020 - https://search.clinicalgenome.org/CCID:005348
Sources: ClinGen
Aminoacidopathy v1.66 MAT1A Sangavi Sivagnanasundram gene: MAT1A was added
gene: MAT1A was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: MAT1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAT1A were set to 9042912; 11320206
Phenotypes for gene: MAT1A were set to methionine adenosyltransferase deficiency MONDO:0009607
Mode of pathogenicity for gene: MAT1A was set to Other
Review for gene: MAT1A was set to GREEN
Added comment: Well established gene-disease association. Dominant negative appears to be the mechanism of disease.

Classified as DEFINITIVE by ClinGen Aminoacidopathy GCEP on 13/09/2019 - https://search.clinicalgenome.org/CCID:005340
Sources: ClinGen
Speech apraxia v0.0 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review; to: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).
Speech apraxia v0.0 FOXP2 Thomas Scerri edited their review of gene: FOXP2: Changed publications: 11586359, 36328423, 38366112
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Changed publications: 30397230, 38366112, 35346573
Speech apraxia v0.0 MKL2 Thomas Scerri edited their review of gene: MKL2: Changed rating: GREEN
Speech apraxia v0.0 MKL2 Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024).
Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).
Cerebral Palsy v1.291 PCLO Clare van Eyk gene: PCLO was added
gene: PCLO was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to PMID: 38693247
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, MIM#608027
Review for gene: PCLO was set to RED
Added comment: 1 individual reported with homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).
Speech apraxia v0.0 CHD3 Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).
Speech apraxia v0.0 KAT6A Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024).
Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 MKL2 Thomas Scerri gene: MKL2 was added
gene: MKL2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to 29463886; 37013900; 38366112
Phenotypes for gene: MKL2 were set to Childhood apraxia of speech; see comments.
Penetrance for gene: MKL2 were set to Complete
Added comment: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024).
Sources: Expert list, Expert Review
Cerebral Palsy v1.291 MYO9A Clare van Eyk gene: MYO9A was added
gene: MYO9A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MYO9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO9A were set to PMID: 38693247
Phenotypes for gene: MYO9A were set to Myasthenic syndrome, congenital, 24, presynaptic, MIM#618198
Review for gene: MYO9A was set to RED
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 PCDH12 Clare van Eyk commented on gene: PCDH12: 2 additional individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.291 MUT Clare van Eyk gene: MUT was added
gene: MUT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to PMID: 38693247
Phenotypes for gene: MUT were set to Methylmalonic aciduria, MIM#251000
Review for gene: MUT was set to AMBER
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Methylmalonic aciduria has a broad clinical spectrum, with neurologic manifestations, such as seizure, encephalopathy, and stroke, frequently reported.
Sources: Literature
Speech apraxia v0.0 KAT6A Thomas Scerri gene: KAT6A was added
gene: KAT6A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 35892268; 38366112; 30245513
Phenotypes for gene: KAT6A were set to Childhood apraxia of speech; see comments.
Penetrance for gene: KAT6A were set to Complete
Review for gene: KAT6A was set to GREEN
Added comment: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Added comment: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; Changed phenotypes: Childhood apraxia of speech, see comments.
Speech apraxia v0.0 FOXP2 Thomas Scerri edited their review of gene: FOXP2: Added comment: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; Changed phenotypes: Childhood apraxia of speech, see comments.
Cerebral Palsy v1.291 MOCS1 Clare van Eyk reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A MIM#252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 MMACHC Clare van Eyk gene: MMACHC was added
gene: MMACHC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to PMID: 38693247
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400
Review for gene: MMACHC was set to AMBER
Added comment: 3 individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variable age at onset with frequent neurological and cardiovascular sequelae.
Sources: Literature
Cerebral Palsy v1.291 MCCC2 Clare van Eyk gene: MCCC2 was added
gene: MCCC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCCC2 were set to PMID: 38693247
Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency, MIM#210210
Review for gene: MCCC2 was set to AMBER
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MCC2D is an autosomal recessive disorder of leucine catabolism. Highly variable clinical phenotype ranging from neonatal onset with severe neurologic involvement to asymptomatic adults. Additional individuals with a clinical diagnosis of CP or overlapping clinical presentation can be found in the literature (e.g. PMID: 9187484, PMID: 10485305)
Sources: Literature
Cerebral Palsy v1.291 LZTR1 Clare van Eyk gene: LZTR1 was added
gene: LZTR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LZTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to PMID: 38693247
Phenotypes for gene: LZTR1 were set to Noonan syndrome 2, MIM#605275
Review for gene: LZTR1 was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 LRP2 Clare van Eyk gene: LRP2 was added
gene: LRP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRP2 were set to PMID: 38693247
Phenotypes for gene: LRP2 were set to Donnai-Barrow syndrome, MIM#222448
Review for gene: LRP2 was set to RED
Added comment: 1 individual reported with compound heterozygous predicted LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. DBS is associated with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.291 LAMA1 Clare van Eyk gene: LAMA1 was added
gene: LAMA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to PMID: 38693247
Phenotypes for gene: LAMA1 were set to Poretti-Boltshauser syndrome, MIM#615960
Review for gene: LAMA1 was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebellar cysts and periventricular white matter abnormalities are common imaging findings in Poretti-Boltshauser syndrome.
Sources: Literature
Mendeliome v1.1840 THRB Achchuthan Shanmugasundram reviewed gene: THRB: Rating: AMBER; Mode of pathogenicity: None; Publications: 37547476; Phenotypes: inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1840 SUMF1 Achchuthan Shanmugasundram changed review comment from: PMID:38863195 reported three unrelated cases with biallelic SUMF1 variants and retinal dystrophy. One of them was a paediatric patient with an attenuated phenotype, while the other two are adult patients with non-syndromic retinal dystrophy.; to: PMID:38863195 reported three unrelated cases with biallelic SUMF1 variants and retinal dystrophy. One of them was a paediatric patient with an attenuated phenotype, while the other two are adult patients with non-syndromic retinal dystrophy.

Retinal dystrophy is part of the multiple sulfatase deficiency phenotype (MIM #272200) typically associated with biallelic variants in SUMF1, and these cases show that presumed hypomorphic variants in SUMF1 may also be associated with non-syndromic retinal dystrophy.
Mendeliome v1.1840 SUMF1 Achchuthan Shanmugasundram reviewed gene: SUMF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38863195; Phenotypes: inherited retinal dystrophy, MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v0.0 CHD3 Thomas Scerri edited their review of gene: CHD3: Changed phenotypes: Childhood apraxia of speech
Speech apraxia v0.0 CHD3 Thomas Scerri gene: CHD3 was added
gene: CHD3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 30397230; 38366112; 35346573
Penetrance for gene: CHD3 were set to Complete
Review for gene: CHD3 was set to GREEN
Added comment: Variant p.Leu915Phe yielded increased activity (PMID: 30397230).
Evidence of reduced penetrance and variable expressivity (PMID: 35346573).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri gene: FOXP2 was added
gene: FOXP2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FOXP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP2 were set to PMID: 11586359; 36328423; 38366112
Phenotypes for gene: FOXP2 were set to Childhood apraxia of speech
Penetrance for gene: FOXP2 were set to Complete
Review for gene: FOXP2 was set to GREEN
Added comment: Sources: Expert list, Expert Review
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.

> PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures. ; to: Craniosynostosis (MONDO:0015469), PRRX1-related
> 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

Agnathia-otocephaly complex, MIM# 202650
>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.

> PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures.
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.

> PMID: 7758948 generated a loss-of-function mutation in the mouse Pmx1 gene. Mice homozygous for the mutant allele died soon after birth and exhibited defects of skeletogenesis, which involved the loss or malformation of craniofacial, limb, and vertebral skeletal structures.
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708). Authors of the more recent publication on Craniosynostosis (PMID: 37154149) cast some doubt on the reports for Agnathia-otocephaly, possible explanations discussed are that this condition is AR and a 2nd hit was missed or another cause was not identified such as variants in OTX2.
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doen't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).; to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doesn't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly don't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.


Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651); to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly doen't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)

>Agnathia-otocephaly complex, 2 x missense variants (1 x het, 1 x hom) and 2 x frameshifts reported (het). The frameshift variants both occur in a poly A tract (PMID: 21294718, PMID: 22674740, PMID: 23444262, PMID: 22211708).
Mendeliome v1.1840 PRRX1 Melanie Marty changed review comment from: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)

Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651); to: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, loss of function variants (PTCs, start loss and partial/full gene del) or missense variants affecting the homeodomain.
> These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent, yielding an estimate for the penetrance of craniosynostosis of 12.5%.
> These results were also supported by immunofluorescence analyses which showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localisation (PMID: 37154149)
> Authors discuss how the previous reports of agnathia-otocephaly don't fit with this new evidence and they showed that a missense variant previously reported in a patient with agnathia-otocephaly p.(Phe113Leu) did not affect nuclear import.


Supporting evidence:
> Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development (PMID: 28366454)

>Prrx1 has been shown to be widely expressed within the mouse coronal suture (PMID: 34376651)
Mendeliome v1.1840 PRRX1 Melanie Marty reviewed gene: PRRX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37154149, 28366454, 34376651; Phenotypes: Craniosynostosis (MONDO:0015469), PRRX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6041 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type 309548 to Intellectual disability, X-linked, FRAXE type 309548
Intellectual disability syndromic and non-syndromic v0.6040 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6039 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6038 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1840 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type 309548 to Intellectual disability, X-linked, FRAXE type, MIM#309548
Mendeliome v1.1839 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1838 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.291 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Cerebral Palsy v1.291 KIF14 Zornitza Stark Gene: kif14 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.291 KIF14 Zornitza Stark Classified gene: KIF14 as Red List (low evidence)
Cerebral Palsy v1.291 KIF14 Zornitza Stark Gene: kif14 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.290 KIF14 Clare van Eyk gene: KIF14 was added
gene: KIF14 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to PMID: 38693247
Phenotypes for gene: KIF14 were set to Microcephaly 20, primary, MIM#617914
Review for gene: KIF14 was set to RED
Added comment: 1 individual reported with biallelic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.290 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from Glutaricaciduria, type I MIM#231670 to Glutaric aciduria, type I MIM#231670
Cerebral Palsy v1.289 GCDH Zornitza Stark Publications for gene: GCDH were set to 30542205; 26593172
Cerebral Palsy v1.288 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Cerebral Palsy v1.288 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Mendeliome v1.1838 RDH14 Zornitza Stark Marked gene: RDH14 as ready
Mendeliome v1.1838 RDH14 Zornitza Stark Gene: rdh14 has been classified as Red List (Low Evidence).
Mendeliome v1.1838 RDH14 Zornitza Stark gene: RDH14 was added
gene: RDH14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RDH14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH14 were set to 34848785
Phenotypes for gene: RDH14 were set to Neurodevelopmental disorder, MONDO:0700092, RDH14-related
Review for gene: RDH14 was set to RED
Added comment: Two related individuals with ID and cerebellar atrophy and homozygous LoF variant reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Marked gene: RDH14 as ready
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Gene: rdh14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark gene: RDH14 was added
gene: RDH14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RDH14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH14 were set to 34848785
Phenotypes for gene: RDH14 were set to Neurodevelopmental disorder, MONDO:0700092, RDH14-related
Review for gene: RDH14 was set to RED
Added comment: Two related individuals with ID and cerebellar atrophy and homozygous LoF variant reported.
Sources: Literature
Brain Calcification v1.96 Zornitza Stark removed gene:GBA from the panel
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Classified gene: HSPD1 as Red List (low evidence)
Cerebral Palsy v1.287 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.286 GBA Zornitza Stark Marked gene: GBA as ready
Cerebral Palsy v1.286 GBA Zornitza Stark Gene: gba has been classified as Red List (Low Evidence).
Cerebral Palsy v1.286 GBA Zornitza Stark Classified gene: GBA as Red List (low evidence)
Cerebral Palsy v1.286 GBA Zornitza Stark Gene: gba has been classified as Red List (Low Evidence).
Cerebral Palsy v1.285 GALC Zornitza Stark Marked gene: GALC as ready
Cerebral Palsy v1.285 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.285 GALC Zornitza Stark Classified gene: GALC as Amber List (moderate evidence)
Cerebral Palsy v1.285 GALC Zornitza Stark Gene: galc has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.284 Zornitza Stark removed gene:AGA from the panel
Cerebral Palsy v1.283 HSPD1 Clare van Eyk gene: HSPD1 was added
gene: HSPD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HSPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPD1 were set to PMID: 38693247
Phenotypes for gene: HSPD1 were set to Leukodystrophy, hypomyelinating, 4, MIM#612233
Review for gene: HSPD1 was set to RED
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. HLD4 has been reported to show rapidly progressive prominent spasticity and developmental regression.
Sources: Literature
Cerebral Palsy v1.283 GCDH Clare van Eyk reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Glutaricaciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.283 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Sources: Literature
Brain Calcification v1.95 GBA Clare van Eyk Deleted their review
Brain Calcification v1.95 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Cerebral Palsy v1.283 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Cerebral Palsy v1.283 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Cerebral Palsy v1.283 FAM20C Zornitza Stark Classified gene: FAM20C as Red List (low evidence)
Cerebral Palsy v1.283 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Cerebral Palsy v1.282 GAMT Zornitza Stark Marked gene: GAMT as ready
Cerebral Palsy v1.282 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Cerebral Palsy v1.282 GAMT Zornitza Stark Classified gene: GAMT as Red List (low evidence)
Cerebral Palsy v1.282 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Cerebral Palsy v1.281 GAMT Clare van Eyk gene: GAMT was added
gene: GAMT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAMT were set to PMID: 38693247
Phenotypes for gene: GAMT were set to Cerebral creatine deficiency syndrome 2, MIM#612736
Review for gene: GAMT was set to AMBER
Added comment: 1 individual reported with CP and biallelic variants (missense and stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebral creatine deficiency syndrome 2 is associated with prominent movement disturbances and can be initially diagnosed as CP (PMID: 31380813).
Sources: Literature
Cerebral Palsy v1.281 FAM20C Clare van Eyk gene: FAM20C was added
gene: FAM20C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to PMID: 38693247
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM#259775
Review for gene: FAM20C was set to RED
Added comment: 1 individual reported with biallelic variants (1 stopgain, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Raine syndrome was originally described as a neonatal osteosclerotic bone dysplasia of early and aggressive onset usually resulting in death within the first few weeks of life, however more recently non-lethal cases with a variable spectrum of features including neurological have been described (PMID: 32299476).
Sources: Literature
Aminoacidopathy v1.66 HGD Zornitza Stark Marked gene: HGD as ready
Aminoacidopathy v1.66 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Aminoacidopathy v1.66 HGD Zornitza Stark Classified gene: HGD as Green List (high evidence)
Aminoacidopathy v1.66 HGD Zornitza Stark Gene: hgd has been classified as Green List (High Evidence).
Aminoacidopathy v1.65 HIBADH Zornitza Stark Marked gene: HIBADH as ready
Aminoacidopathy v1.65 HIBADH Zornitza Stark Gene: hibadh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.65 HIBADH Zornitza Stark Classified gene: HIBADH as Red List (low evidence)
Aminoacidopathy v1.65 HIBADH Zornitza Stark Gene: hibadh has been classified as Red List (Low Evidence).
Aminoacidopathy v1.64 HPD Zornitza Stark Marked gene: HPD as ready
Aminoacidopathy v1.64 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Aminoacidopathy v1.64 HPD Zornitza Stark Classified gene: HPD as Green List (high evidence)
Aminoacidopathy v1.64 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Mendeliome v1.1837 HYKK Zornitza Stark Marked gene: HYKK as ready
Mendeliome v1.1837 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
Mendeliome v1.1837 HYKK Zornitza Stark gene: HYKK was added
gene: HYKK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HYKK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYKK were set to 23242558
Phenotypes for gene: HYKK were set to inborn disorder of lysine and hydroxylysine metabolism MONDO:0017351
Review for gene: HYKK was set to RED
Added comment: No known gene-disease association as classified by ClinGen Aminoacidopathy GCEP on 14/07/2023 - https://search.clinicalgenome.org/CCID:005104 HYKK has been reported as a disorders of lysine, hydroxylysine, and tryptophan metabolism by ICIMD however there are no reported pathogenic variants in this gene to support the gene-disease association.
Sources: Literature
Cerebral Palsy v1.281 GALC Clare van Eyk gene: GALC was added
gene: GALC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to PMID: 38693247
Phenotypes for gene: GALC were set to Krabbe disease, MIM#245200
Review for gene: GALC was set to AMBER
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Krabbe disease is associated with progressive spasticity with variable at age at onset. Later onset can be associated with a slower progression and can mimic CP.
Sources: Literature
Aminoacidopathy v1.63 HYKK Zornitza Stark Marked gene: HYKK as ready
Aminoacidopathy v1.63 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
Aminoacidopathy v1.63 HYKK Zornitza Stark Classified gene: HYKK as Red List (low evidence)
Aminoacidopathy v1.63 HYKK Zornitza Stark Gene: hykk has been classified as Red List (Low Evidence).
Mendeliome v1.1836 KMO Zornitza Stark Marked gene: KMO as ready
Mendeliome v1.1836 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
Mendeliome v1.1836 KMO Zornitza Stark gene: KMO was added
gene: KMO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KMO were set to 28187857; 24189070
Phenotypes for gene: KMO were set to pellagra MONDO:0019975
Review for gene: KMO was set to RED
Added comment: Classified as no known disease relationship by ClinGen Aminoacidopathy GCEP on 12/05/2023 - https://search.clinicalgenome.org/CCID:005248 Only two knock out mouse models have ben reported that exhibited behavioural changes including memory impairment and anxiety like behaviour. Not reported as disease causing in any affected individuals at this stage and no evidence of any inborn errors of amino acid metabolism.
Sources: Literature
Aminoacidopathy v1.62 KMO Zornitza Stark Marked gene: KMO as ready
Aminoacidopathy v1.62 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
Aminoacidopathy v1.62 KMO Zornitza Stark Classified gene: KMO as Red List (low evidence)
Aminoacidopathy v1.62 KMO Zornitza Stark Gene: kmo has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v1.6 MCEE Zornitza Stark Marked gene: MCEE as ready
Vitamin metabolism disorders v1.6 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Cerebral Palsy v1.281 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Cerebral Palsy v1.281 DDX59 Zornitza Stark Gene: ddx59 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.281 DDX59 Zornitza Stark Classified gene: DDX59 as Red List (low evidence)
Cerebral Palsy v1.281 DDX59 Zornitza Stark Gene: ddx59 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Classified gene: DHCR7 as Red List (low evidence)
Cerebral Palsy v1.280 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Classified gene: DIAPH1 as Red List (low evidence)
Cerebral Palsy v1.279 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Marked gene: LMNA as ready
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Classified gene: LMNA as Green List (high evidence)
Deafness_IsolatedAndComplex v1.184 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Classified gene: DUOX2 as Red List (low evidence)
Cerebral Palsy v1.278 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.277 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Cerebral Palsy v1.277 EPG5 Zornitza Stark Gene: epg5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.277 EPG5 Zornitza Stark Classified gene: EPG5 as Red List (low evidence)
Cerebral Palsy v1.277 EPG5 Zornitza Stark Gene: epg5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.276 ERCC8 Zornitza Stark Publications for gene: ERCC8 were set to 33528536; 30279719
Cerebral Palsy v1.275 ERCC8 Clare van Eyk reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Cockayne syndrome MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.275 EPG5 Clare van Eyk gene: EPG5 was added
gene: EPG5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to PMID: 38693247
Phenotypes for gene: EPG5 were set to Vici syndrome, MIM#242840
Review for gene: EPG5 was set to RED
Added comment: 1 individual reported with a homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Vici syndrome is a neurodevelopmental and immunological disorder affecting multiple systems. Structural abnormalities of the brain along with profound psychomotor retardation have been reported.
Sources: Literature
Cerebral Palsy v1.275 DUOX2 Clare van Eyk gene: DUOX2 was added
gene: DUOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to PMID: 38693247
Phenotypes for gene: DUOX2 were set to Thyroid dyshormonogenesis 6, MIM#607200
Review for gene: DUOX2 was set to RED
Added comment: 1 individual reported with biallelic variants (1 missense, 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Congenital hypothyroidism is associated with increased risk of cerebral palsy if untreated, amongst other developmental sequelae.
Sources: Literature
Deafness_IsolatedAndComplex v1.183 LMNA Rylee Peters gene: LMNA was added
gene: LMNA was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNA were set to PMID: 32913962
Phenotypes for gene: LMNA were set to Laminopathy (MONDO#0021106), LMNA-related
Review for gene: LMNA was set to GREEN
Added comment: PMID: 32913962; Total of 13 individuals heterozygous for the R349W variant. Recurrent phenotypes in these individuals include partial lipodystrophy, proteinuric nephropathy, cardiopathies and sensorineural hearing impairment.
Hearing impairment was identified in 66% of the patients (6/9 individuals, 4 were not reported) and ranged from reduction or complete sensorineural deafness.
Sources: Literature
Cerebral Palsy v1.275 DIAPH1 Clare van Eyk gene: DIAPH1 was added
gene: DIAPH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DIAPH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 38693247; 34125151
Phenotypes for gene: DIAPH1 were set to Seizures, cortical blindness, and microcephaly syndrome, MIM#616632
Review for gene: DIAPH1 was set to AMBER
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

De novo and rare, transmitted damaging variants in DIAPH1 have been reported as a risk factor for Moyamoya disease resulting in ischemic stroke, however CP was not reported as a sequelae in this case series (PMID:34125151).
Sources: Literature
Cerebral Palsy v1.275 DHCR7 Clare van Eyk gene: DHCR7 was added
gene: DHCR7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to PMID: 38693247
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM#270400
Review for gene: DHCR7 was set to RED
Added comment: 1 individual reported with biallelic P/LP variants (1 missense, 1 frameshift) in a large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia in infancy followed by later hypertonia are described, usually presenting with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.275 DDX59 Clare van Eyk edited their review of gene: DDX59: Changed rating: RED
Cerebral Palsy v1.275 DDX59 Clare van Eyk gene: DDX59 was added
gene: DDX59 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to PMID: 38693247
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, MIM#174300
Added comment: 1 individual reported with biallelic variants (1 missense, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. OFD5 has not been previously associated with CP, however white matter abnormalities on MRI have been reported.
Sources: Literature
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson changed review comment from: Involved in the metabolism of cobalamin (vitamin B12). Serum B12 levels are measures as part of the diagnosis of this condition.
Sources: Expert list; to: It is not directly involved in cobalamin (vitamin B12) metabolism, but serum B12 levels are measured in diagnosing this condition. Included as a differential diagnosis.
Sources: Expert list
Vitamin metabolism disorders v1.6 MUT Bryony Thompson changed review comment from: Involved in cobalamin (vitamin B12) metabolism. Serum B12 levels are measured in the diagnosis of this condition.
Sources: Expert list; to: It is not directly involved in cobalamin (vitamin B12) metabolism, but serum B12 levels are measured in diagnosing this condition. Included as a differential diagnosis.
Sources: Expert list
Aminoacidopathy v1.61 KYNU Zornitza Stark Marked gene: KYNU as ready
Aminoacidopathy v1.61 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Aminoacidopathy v1.61 KYNU Zornitza Stark Classified gene: KYNU as Green List (high evidence)
Aminoacidopathy v1.61 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Marked gene: LMBRD1 as ready
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Classified gene: LMBRD1 as Green List (high evidence)
Aminoacidopathy v1.60 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson Classified gene: MCEE as Green List (high evidence)
Vitamin metabolism disorders v1.6 MCEE Bryony Thompson Gene: mcee has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.5 MCEE Bryony Thompson gene: MCEE was added
gene: MCEE was added to Vitamin metabolism disorders. Sources: Expert list
Mode of inheritance for gene: MCEE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCEE were set to 20301409
Phenotypes for gene: MCEE were set to methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency MONDO:0009615
Review for gene: MCEE was set to GREEN
gene: MCEE was marked as current diagnostic
Added comment: Involved in the metabolism of cobalamin (vitamin B12). Serum B12 levels are measures as part of the diagnosis of this condition.
Sources: Expert list
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Marked gene: MUT as ready
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Gene: mut has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Classified gene: MUT as Green List (high evidence)
Vitamin metabolism disorders v1.4 MUT Bryony Thompson Gene: mut has been classified as Green List (High Evidence).
Vitamin metabolism disorders v1.3 MUT Bryony Thompson gene: MUT was added
gene: MUT was added to Vitamin metabolism disorders. Sources: Expert list
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to 20301409
Phenotypes for gene: MUT were set to methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency MONDO:0009612
Review for gene: MUT was set to GREEN
gene: MUT was marked as current diagnostic
Added comment: Involved in cobalamin (vitamin B12) metabolism. Serum B12 levels are measured in the diagnosis of this condition.
Sources: Expert list
Aminoacidopathy v1.59 LMBRD1 Sangavi Sivagnanasundram gene: LMBRD1 was added
gene: LMBRD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: LMBRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMBRD1 were set to 20301503; 19136951; 32875039; 20127417; 21303734
Phenotypes for gene: LMBRD1 were set to methylmalonic aciduria and homocystinuria type cblF MONDO:0010183
Review for gene: LMBRD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 26/03/2021 - https://search.clinicalgenome.org/CCID:005290

Reported in multiple individuals with evidence of defective cobalamin metabolism.
Mechanism of disease appears to be loss of function leading to a defective release of cobalamin from lysosomes.
Sources: ClinGen
Aminoacidopathy v1.59 KYNU Sangavi Sivagnanasundram edited their review of gene: KYNU: Changed publications: 37499065, 28792876, 33942433, 31923704, 17334708, 34200361
Aminoacidopathy v1.59 KYNU Sangavi Sivagnanasundram gene: KYNU was added
gene: KYNU was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 37499065, 28792876, 33942433, 31923704, 17334708, 34200361
Phenotypes for gene: KYNU were set to vertebral, cardiac, renal, and limb defects syndrome 2 MONDO:0060555
Review for gene: KYNU was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 12/05/2023 - https://search.clinicalgenome.org/CCID:005259

Reported in >5 unrelated probands with an error in synthesis of NAD from tryptophan. Mouse model recapitulates human phenotype while on a NAD-restricted diet.
Sources: ClinGen
Aminoacidopathy v1.59 KMO Sangavi Sivagnanasundram gene: KMO was added
gene: KMO was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: KMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KMO were set to 28187857, 24189070
Phenotypes for gene: KMO were set to pellagra MONDO:0019975
Review for gene: KMO was set to RED
Added comment: Classified as no known disease relationship by ClinGen Aminoacidopathy GCEP on 12/05/2023 - https://search.clinicalgenome.org/CCID:005248

Only two knock out mouse models have ben reported that exhibited behavioural changes including memory impairment and anxiety like behaviour. Not reported as disease causing in any affected individuals at this stage and no evidence of any inborn errors of amino acid metabolism.
Sources: ClinGen
Aminoacidopathy v1.59 HYKK Sangavi Sivagnanasundram gene: HYKK was added
gene: HYKK was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HYKK was set to Unknown
Publications for gene: HYKK were set to 23242558
Phenotypes for gene: HYKK were set to inborn disorder of lysine and hydroxylysine metabolism MONDO:0017351
Review for gene: HYKK was set to RED
Added comment: No known gene-disease association as classified by ClinGen Aminoacidopathy GCEP on 14/07/2023 - https://search.clinicalgenome.org/CCID:005104

HYKK has been reported as a disorders of lysine, hydroxylysine, and tryptophan metabolism by ICIMD however there are no reported pathogenic variants in this gene to support the gene-disease association.
Sources: ClinGen
Aminoacidopathy v1.59 HPD Sangavi Sivagnanasundram gene: HPD was added
gene: HPD was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HPD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HPD were set to 10942115, 11073718, 28649543, 11073718, 31342835
Phenotypes for gene: HPD were set to tyrosinemia type III MONDO:0010162; hawkinsinuria MONDO:0007700
Review for gene: HPD was set to GREEN
Added comment: Tyrosinemia type III - AR and Hawkinsinuria - AD

ClinGen classified limited evidence for the AD gene-disease association on 17/11/2023 and definitive for AR gene-disease association on 29/06/2020.

Established gene-disease association. Reported individuals reported with inborn errors of amino acid metabolism.
Sources: ClinGen
Aminoacidopathy v1.59 HIBADH Sangavi Sivagnanasundram gene: HIBADH was added
gene: HIBADH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIBADH were set to 34176136; 35174513
Phenotypes for gene: HIBADH were set to 3-hydroxyisobutyric aciduria MONDO:0009371
Review for gene: HIBADH was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 24/03/2023 - https://search.clinicalgenome.org/CCID:005058

Reported in 3 probands however there is lack of clinical evidence to show that hydroxyisobutyrate dehydrogenase deficiency leads to their clinical phenotype.
Sources: ClinGen
Aminoacidopathy v1.59 HGD Sangavi Sivagnanasundram gene: HGD was added
gene: HGD was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HGD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HGD were set to 8782815; 9529363; 9154114; 9674916
Phenotypes for gene: HGD were set to alkaptonuria MONDO:0008753
Review for gene: HGD was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 29/06/2020 - https://search.clinicalgenome.org/CCID:005055

Well established gene-disease association with reported individuals showing evidence of abnormal biochemical function.
Sources: ClinGen
Hydrops fetalis v0.313 RAPSN Zornitza Stark Publications for gene: RAPSN were set to 18252226
Hydrops fetalis v0.312 RAPSN Zornitza Stark Classified gene: RAPSN as Green List (high evidence)
Hydrops fetalis v0.312 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Aminoacidopathy v1.59 HAL Zornitza Stark Marked gene: HAL as ready
Aminoacidopathy v1.59 HAL Zornitza Stark Gene: hal has been classified as Red List (Low Evidence).
Aminoacidopathy v1.59 HAL Zornitza Stark Classified gene: HAL as Red List (low evidence)
Aminoacidopathy v1.59 HAL Zornitza Stark Gene: hal has been classified as Red List (Low Evidence).
Aminoacidopathy v1.58 HAAO Zornitza Stark Marked gene: HAAO as ready
Aminoacidopathy v1.58 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Aminoacidopathy v1.58 HAAO Zornitza Stark Classified gene: HAAO as Green List (high evidence)
Aminoacidopathy v1.58 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Marked gene: GSTZ1 as ready
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Classified gene: GSTZ1 as Red List (low evidence)
Aminoacidopathy v1.57 GSTZ1 Zornitza Stark Gene: gstz1 has been classified as Red List (Low Evidence).
Aminoacidopathy v1.56 GSS Zornitza Stark Marked gene: GSS as ready
Aminoacidopathy v1.56 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Aminoacidopathy v1.56 GSS Zornitza Stark Classified gene: GSS as Green List (high evidence)
Aminoacidopathy v1.56 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Aminoacidopathy v1.55 GNMT Zornitza Stark Marked gene: GNMT as ready
Aminoacidopathy v1.55 GNMT Zornitza Stark Gene: gnmt has been classified as Red List (Low Evidence).
Aminoacidopathy v1.55 GNMT Zornitza Stark Classified gene: GNMT as Red List (low evidence)
Aminoacidopathy v1.55 GNMT Zornitza Stark Gene: gnmt has been classified as Red List (Low Evidence).
Aminoacidopathy v1.54 GLUL Zornitza Stark Marked gene: GLUL as ready
Aminoacidopathy v1.54 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Aminoacidopathy v1.54 GLUL Zornitza Stark Classified gene: GLUL as Green List (high evidence)
Aminoacidopathy v1.54 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Classified gene: GLUD1 as Green List (high evidence)
Aminoacidopathy v1.53 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.52 GLS Zornitza Stark Marked gene: GLS as ready
Aminoacidopathy v1.52 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Aminoacidopathy v1.52 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Aminoacidopathy v1.52 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Aminoacidopathy v1.51 GLDC Zornitza Stark Marked gene: GLDC as ready
Aminoacidopathy v1.51 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Aminoacidopathy v1.51 GLDC Zornitza Stark Classified gene: GLDC as Green List (high evidence)
Aminoacidopathy v1.51 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Aminoacidopathy v1.50 GCSH Zornitza Stark Marked gene: GCSH as ready
Aminoacidopathy v1.50 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Aminoacidopathy v1.50 GCSH Zornitza Stark Classified gene: GCSH as Green List (high evidence)
Aminoacidopathy v1.50 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Aminoacidopathy v1.49 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Aminoacidopathy v1.49 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.49 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Aminoacidopathy v1.49 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Aminoacidopathy v1.48 GCDH Zornitza Stark Marked gene: GCDH as ready
Aminoacidopathy v1.48 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Aminoacidopathy v1.48 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Aminoacidopathy v1.48 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Skeletal dysplasia v0.281 FUZ Zornitza Stark Marked gene: FUZ as ready
Skeletal dysplasia v0.281 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Fetal anomalies v1.249 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Neural tube defects 182940 to Neural tube defects 182940; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Fetal anomalies v1.248 FUZ Zornitza Stark Publications for gene: FUZ were set to 21840926
Fetal anomalies v1.247 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.281 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Marked gene: FUZ as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.15 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Mendeliome v1.1835 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469 to {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Mendeliome v1.1834 FUZ Zornitza Stark Publications for gene: FUZ were set to 21840926
Ciliopathies v1.54 FUZ Zornitza Stark Marked gene: FUZ as ready
Ciliopathies v1.54 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Ciliopathies v1.54 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Skeletal Dysplasia_Fetal v0.223 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Ciliopathy_MONDO_0005308; skeletal ciliopathy to Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Marked gene: ATXN7L3 as ready
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Marked gene: ATXN7L3 as ready
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Gene: atxn7l3 has been classified as Green List (High Evidence).
Mendeliome v1.1833 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related
Mendeliome v1.1832 STK33 Zornitza Stark Marked gene: STK33 as ready
Mendeliome v1.1832 STK33 Zornitza Stark Gene: stk33 has been classified as Red List (Low Evidence).
Mendeliome v1.1832 STK33 Zornitza Stark gene: STK33 was added
gene: STK33 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STK33 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK33 were set to 34155512; 29155043
Phenotypes for gene: STK33 were set to Spermatogenic failure 93, MIM#620849
Review for gene: STK33 was set to RED
Added comment: Four brothers with a homozygous variant and an animal model.
Sources: Literature
Mendeliome v1.1831 NAT6 Zornitza Stark Marked gene: NAT6 as ready
Mendeliome v1.1831 NAT6 Zornitza Stark Gene: nat6 has been classified as Red List (Low Evidence).
Mendeliome v1.1831 NAT6 Zornitza Stark gene: NAT6 was added
gene: NAT6 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: NAT6.
Mode of inheritance for gene: NAT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT6 were set to 34805998
Phenotypes for gene: NAT6 were set to Auroneurodental syndrome, MIM# 620830
Review for gene: NAT6 was set to RED
Added comment: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.

HGNC approved name is NAA80.
Sources: Literature
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark changed review comment from: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.
Sources: Literature; to: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.

HGNC approved name is NAA80.

Sources: Literature
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark Marked gene: NAT6 as ready
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark Gene: nat6 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.183 NAT6 Zornitza Stark gene: NAT6 was added
gene: NAT6 was added to Deafness_IsolatedAndComplex. Sources: Literature
new gene name tags were added to gene: NAT6.
Mode of inheritance for gene: NAT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT6 were set to 34805998
Phenotypes for gene: NAT6 were set to Auroneurodental syndrome, MIM# 620830
Review for gene: NAT6 was set to RED
Added comment: Case report of two brothers with homozygous missense variant and deafness, periodic hypotonia and dental anomalies.
Sources: Literature
Aminoacidopathy v1.47 HAL Sangavi Sivagnanasundram gene: HAL was added
gene: HAL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAL were set to 15806399
Phenotypes for gene: HAL were set to histidinemia MONDO:0009345
Review for gene: HAL was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 17/11/2023 - https://search.clinicalgenome.org/CCID:005031

Metabolic disorder appears to be benign in most reported affected individuals.
Sources: ClinGen
Aminoacidopathy v1.47 HAAO Sangavi Sivagnanasundram gene: HAAO was added
gene: HAAO was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: HAAO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAAO were set to 37499065; 28792876; 33942433
Phenotypes for gene: HAAO were set to vertebral, cardiac, renal, and limb defects syndrome 1 MONDO:0060554
Review for gene: HAAO was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 24/06/2022 - https://search.clinicalgenome.org/CCID:005026

Reported in >3 unrelated probands with biochemical abnormalities. LoF appears to be the mechanism of disease.
Sources: ClinGen
Aminoacidopathy v1.47 GSTZ1 Sangavi Sivagnanasundram gene: GSTZ1 was added
gene: GSTZ1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSTZ1 were set to 27876694
Phenotypes for gene: GSTZ1 were set to maleylacetoacetate isomerase deficiency MONDO:0060527
Review for gene: GSTZ1 was set to RED
Added comment: Classified Moderate by ClinGen Aminoacidopathy GCEP on 09/09/2022 -https://search.clinicalgenome.org/CCID:005017

6 probands have been reported with mild hypersuccinylacetonaemia (MHSA). The reported individuals remained well without receiving any treatment or change in diet.
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.6036 PTEN Ain Roesley Phenotypes for gene: PTEN were changed from Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309 to Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309; PTEN hamartoma tumor syndrome MONDO:0017623
Overgrowth v1.12 PTEN Ain Roesley Phenotypes for gene: PTEN were changed from Cowden syndrome 1, MIM# 158350; Macrocephaly/autism syndrome, MIM# 605309 to Cowden syndrome 1, MIM# 158350; Macrocephaly/autism syndrome, MIM# 605309; PTEN hamartoma tumor syndrome MONDO:0017623
Aminoacidopathy v1.47 GSS Sangavi Sivagnanasundram gene: GSS was added
gene: GSS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSS were set to 17397529
Phenotypes for gene: GSS were set to inherited glutathione synthetase deficiency MONDO:0017909
Review for gene: GSS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 26/04/2019 -https://search.clinicalgenome.org/CCID:005016

Well established gene-disease association with reported individuals having errors in glutathione metabolism.
Sources: ClinGen
Aminoacidopathy v1.47 GNMT Sangavi Sivagnanasundram gene: GNMT was added
gene: GNMT was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GNMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNMT were set to 11810299; 14739680
Phenotypes for gene: GNMT were set to glycine N-methyltransferase deficiency MONDO:0011698
Review for gene: GNMT was set to RED
Added comment: Classified Limited by ClinGen Aminoacidopathy GCEP on 12/12/2022 -https://search.clinicalgenome.org/CCID:004979
Sources: ClinGen
Aminoacidopathy v1.47 GLUL Sangavi Sivagnanasundram gene: GLUL was added
gene: GLUL was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLUL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLUL were set to 25870278; 20140959; 30053506
Phenotypes for gene: GLUL were set to congenital brain dysgenesis due to glutamine synthetase deficiency MONDO:0012393
Review for gene: GLUL was set to GREEN
Added comment: Classified Moderate by ClinGen Aminoacidopathy GCEP on 12/12/2022 - https://search.clinicalgenome.org/CCID:004969

At least 5 probands from 4 unrelated families reported with glutamine deficiency.
Sources: ClinGen
Aminoacidopathy v1.47 GLUD1 Sangavi Sivagnanasundram gene: GLUD1 was added
gene: GLUD1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLUD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLUD1 were set to 9571255; 11214910; 26759084
Phenotypes for gene: GLUD1 were set to hyperinsulinism-hyperammonemia syndrome MONDO:0011717
Review for gene: GLUD1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 13/11/2020 - https://search.clinicalgenome.org/CCID:004968

Well-established gene disease association with reported individuals having a metabolic abnormality.
Sources: ClinGen
Mendeliome v1.1830 FAM177A1 Zornitza Stark Marked gene: FAM177A1 as ready
Mendeliome v1.1830 FAM177A1 Zornitza Stark Gene: fam177a1 has been classified as Green List (High Evidence).
Mendeliome v1.1830 FAM177A1 Zornitza Stark Phenotypes for gene: FAM177A1 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, FAM177A1-related
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Marked gene: FAM177A1 as ready
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Phenotypes for gene: FAM177A1 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, FAM177a1-related
Skeletal dysplasia v0.280 PISD Zornitza Stark Phenotypes for gene: PISD were changed from Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses to Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses, MONDO:0100510
Skeletal dysplasia v0.279 PISD Zornitza Stark Phenotypes for gene: PISD were changed from Spondylometaphyseal dysplasia with large epiphyses to Liberfarb syndrome MIM# 618889; Spondylometaphyseal dysplasia with large epiphyses
Skeletal dysplasia v0.278 PISD Zornitza Stark Classified gene: PISD as Green List (high evidence)
Skeletal dysplasia v0.278 PISD Zornitza Stark Gene: pisd has been classified as Green List (High Evidence).
Mendeliome v1.1829 ERF Zornitza Stark Phenotypes for gene: ERF were changed from Craniosynostosis 4, MIM# 600775; Chitayat syndrome, MIM# 617180 to Craniosynostosis 4, MIM# 600775; Chitayat syndrome, MIM# 617180; Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Mendeliome v1.1828 ERF Zornitza Stark edited their review of gene: ERF: Changed phenotypes: Craniosynostosis 4, MIM# 600775, Chitayat syndrome, MIM# 617180, Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Rasopathy v0.105 ERF Zornitza Stark Marked gene: ERF as ready
Rasopathy v0.105 ERF Zornitza Stark Gene: erf has been classified as Green List (High Evidence).
Rasopathy v0.105 ERF Zornitza Stark Phenotypes for gene: ERF were changed from Noonan syndrome-like with or without craniosynostosis to Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related
Rasopathy v0.104 ERF Zornitza Stark reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Marked gene: ANO4 as ready
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Gene: ano4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Classified gene: ANO4 as Green List (high evidence)
Genetic Epilepsy v1.26 ANO4 Zornitza Stark Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6034 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to 29315614
Intellectual disability syndromic and non-syndromic v0.6033 SLC6A1 Zornitza Stark edited their review of gene: SLC6A1: Added comment: Haploinsufficiency established as the mechanism.; Changed publications: 29315614, 38781976
Intellectual disability syndromic and non-syndromic v0.6033 MSL2 Zornitza Stark Phenotypes for gene: MSL2 were changed from Developmental disorders; autism to Neurodevelopmental disorder, MONDO:0700092, MSL2-related
Mendeliome v1.1828 MSL2 Zornitza Stark Phenotypes for gene: MSL2 were changed from Developmental disorders; autism to Neurodevelopmental disorder, MONDO:0700092, MSL2-related
Mendeliome v1.1827 MSL2 Zornitza Stark Publications for gene: MSL2 were set to 31332282; 33057194
Mendeliome v1.1826 MSL2 Zornitza Stark Classified gene: MSL2 as Green List (high evidence)
Mendeliome v1.1826 MSL2 Zornitza Stark Gene: msl2 has been classified as Green List (High Evidence).
Mendeliome v1.1825 HGF Zornitza Stark Phenotypes for gene: HGF were changed from Deafness, autosomal recessive 39, MIM# 608265 to Deafness, autosomal recessive 39, MIM# 608265; Lymphoedema, MONDO:0019297, HGF-related
Mendeliome v1.1824 HGF Zornitza Stark Publications for gene: HGF were set to 19576567
Mendeliome v1.1823 HGF Zornitza Stark Mode of inheritance for gene: HGF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1822 HGF Zornitza Stark edited their review of gene: HGF: Added comment: More than 10 families reported with childhood- to late-onset lymphoedema.; Changed publications: 19576567, 38676400, 38791500; Changed phenotypes: Deafness, autosomal recessive 39, MIM# 608265, Lymphoedema, MONDO:0019297, HGF-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Marked gene: HGF as ready
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Classified gene: HGF as Green List (high evidence)
Lymphoedema_nonsyndromic v0.39 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.38 HGF Zornitza Stark gene: HGF was added
gene: HGF was added to Lymphoedema_nonsyndromic. Sources: Literature
Mode of inheritance for gene: HGF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HGF were set to 38676400; 38791500
Phenotypes for gene: HGF were set to Lymphoedema, MONDO:0019297, HGF-related
Review for gene: HGF was set to GREEN
Added comment: More than 10 families reported with childhood- to late-onset lymphoedema.
Sources: Literature
Mendeliome v1.1822 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Inborn error of immunity, MONDO:0003778, TKFC-related
Mendeliome v1.1821 TKFC Zornitza Stark edited their review of gene: TKFC: Added comment: Single individual reported with homozygous variant and isolated immunodeficiency.; Changed publications: 32004446'38697782; Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Inborn error of immunity, MONDO:0003778, TKFC-related
Combined Immunodeficiency v1.66 TKFC Zornitza Stark changed review comment from: Single individual reported with homozygous variant.
Sources: Literature; to: Single individual reported with homozygous variant.

Note relationship with syndromic ID also postulated.
Sources: Literature
Combined Immunodeficiency v1.66 TKFC Zornitza Stark Marked gene: TKFC as ready
Combined Immunodeficiency v1.66 TKFC Zornitza Stark Gene: tkfc has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.66 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 38697782
Phenotypes for gene: TKFC were set to Inborn error of immunity, MONDO:0003778, TKFC-related
Review for gene: TKFC was set to RED
Added comment: Single individual reported with homozygous variant.
Sources: Literature
Mendeliome v1.1821 CYLC1 Zornitza Stark Marked gene: CYLC1 as ready
Mendeliome v1.1821 CYLC1 Zornitza Stark Gene: cylc1 has been classified as Green List (High Evidence).
Mendeliome v1.1821 CYLC1 Zornitza Stark Classified gene: CYLC1 as Green List (high evidence)
Mendeliome v1.1821 CYLC1 Zornitza Stark Gene: cylc1 has been classified as Green List (High Evidence).
Mendeliome v1.1820 CYLC1 Zornitza Stark gene: CYLC1 was added
gene: CYLC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CYLC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CYLC1 were set to Spermatogenic failure, X-linked, 8, MIM# 301119
Review for gene: CYLC1 was set to GREEN
Added comment: 19 individuals and a mouse model reported.
Sources: Literature
Aminoacidopathy v1.47 GLS Sangavi Sivagnanasundram gene: GLS was added
gene: GLS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 29468182, 30575854, 30970188; 16641247
Phenotypes for gene: GLS were set to glutaminase deficiency MONDO:0600001
Review for gene: GLS was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 09/07/2021 - https://search.clinicalgenome.org/CCID:004965

6 probands have been reported with glutaminase deficiency. Nonsense, framshift and missense variants have been reported. 5’UTR repeat expansion (680-1500 repeats; normal range 8-16 repeats) has also been reported.
Mouse model was also conducted that recapitulates the human phenotype (PMID: 16641247).
Sources: ClinGen
Aminoacidopathy v1.47 GLDC Sangavi Sivagnanasundram gene: GLDC was added
gene: GLDC was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GLDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLDC were set to 25736695; 27362913; 26179960; 24407464
Phenotypes for gene: GLDC were set to glycine encephalopathy MONDO:0011612
Review for gene: GLDC was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 06/02/2019 - https://search.clinicalgenome.org/CCID:004962

Well reported gene-disease association with reported individuals present with glycine encephalopathy.
Sources: ClinGen
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Marked gene: FUZ as ready
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Classified gene: FUZ as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.222 FUZ Zornitza Stark Gene: fuz has been classified as Green List (High Evidence).
Bone Marrow Failure v1.92 FLT3LG Ain Roesley Marked gene: FLT3LG as ready
Bone Marrow Failure v1.92 FLT3LG Ain Roesley Gene: flt3lg has been classified as Red List (Low Evidence).
Mendeliome v1.1819 FLT3LG Ain Roesley Marked gene: FLT3LG as ready
Mendeliome v1.1819 FLT3LG Ain Roesley Gene: flt3lg has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.92 FLT3LG Ain Roesley gene: FLT3LG was added
gene: FLT3LG was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: FLT3LG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLT3LG were set to 38701783
Phenotypes for gene: FLT3LG were set to Increased susceptibility to infections
Review for gene: FLT3LG was set to RED
gene: FLT3LG was marked as current diagnostic
Added comment: 3x sibs from a consanguineous family with a homozygous frameshift variant p.(Ser118Alafs*23)
recurrent infections and hypoplastic bone marrow with marked reduction in HPSCs
KO mice recapitulated BM findings

over a period of 5 (P1), 9 (P2), and 19 (P3) years of follow-up, all 3 were found to have moderate anaemia.
Total platelet counts and morphology decreased in 2 siblings.
Total WBC oscillated between low and normal
Eosinophils, basophils were in normal range
Neutrophils were in the lower part of the control range, ocassiannly lower
total lymphocyte counts were normal
Sources: Literature
Mendeliome v1.1819 FLT3LG Ain Roesley gene: FLT3LG was added
gene: FLT3LG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FLT3LG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLT3LG were set to 38701783
Phenotypes for gene: FLT3LG were set to Increased susceptibility to infections
Review for gene: FLT3LG was set to RED
gene: FLT3LG was marked as current diagnostic
Added comment: 3x sibs from a consanguineous family with a homozygous frameshift variant p.(Ser118Alafs*23)
recurrent infections and hypoplastic bone marrow with marked reduction in HPSCs
KO mice recapitulated BM findings

over a period of 5 (P1), 9 (P2), and 19 (P3) years of follow-up, all 3 were found to have moderate anaemia.
Total platelet counts and morphology decreased in 2 siblings.
Total WBC oscillated between low and normal
Eosinophils, basophils were in normal range
Neutrophils were in the lower part of the control range, ocassiannly lower
total lymphocyte counts were normal
Sources: Literature
Lymphoedema_nonsyndromic v0.37 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452; 38820174
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452; 38820174
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Classified gene: TIE1 as Green List (high evidence)
Lymphoedema_nonsyndromic v0.36 TIE1 Ain Roesley Gene: tie1 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.35 TIE1 Ain Roesley edited their review of gene: TIE1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lymphoedema_nonsyndromic v0.35 TIE1 Ain Roesley reviewed gene: TIE1: Rating: ; Mode of pathogenicity: None; Publications: 38820174; Phenotypes: Lymphatic malformation 11, MIM# 619401; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v1.1818 TIE1 Ain Roesley Classified gene: TIE1 as Green List (high evidence)
Mendeliome v1.1818 TIE1 Ain Roesley Gene: tie1 has been classified as Green List (High Evidence).
Mendeliome v1.1818 TIE1 Ain Roesley Publications for gene: TIE1 were set to 32947856; 24764452
Mendeliome v1.1817 TIE1 Ain Roesley reviewed gene: TIE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38820174; Phenotypes: Lymphatic malformation 11, MIM# 619401; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1817 MSL2 Sangavi Sivagnanasundram reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38815585, 38702431; Phenotypes: MSL2-Related Developmental Disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6032 MSL2 Sangavi Sivagnanasundram reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38815585, 38702431; Phenotypes: MSL2-Related Developmental Disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1817 PISD Sangavi Sivagnanasundram reviewed gene: PISD: Rating: GREEN; Mode of pathogenicity: None; Publications: 38801004; Phenotypes: Liberfarb syndrome MONDO:0030045; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.277 PISD Sangavi Sivagnanasundram reviewed gene: PISD: Rating: GREEN; Mode of pathogenicity: None; Publications: 38801004; Phenotypes: Liberfarb syndrome MONDO:0030045; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1817 ATXN7L3 Chirag Patel Classified gene: ATXN7L3 as Green List (high evidence)
Mendeliome v1.1817 ATXN7L3 Chirag Patel Gene: atxn7l3 has been classified as Green List (High Evidence).
Mendeliome v1.1816 ATXN7L3 Chirag Patel gene: ATXN7L3 was added
gene: ATXN7L3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN7L3 were set to PMID: 38753057
Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: ATXN7L3 was set to GREEN
gene: ATXN7L3 was marked as current diagnostic
Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities.

A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality.

Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51).
Sources: Literature
Mendeliome v1.1815 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Mendeliome v1.1815 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Mendeliome v1.1814 FAM177A1 Chirag Patel gene: FAM177A1 was added
gene: FAM177A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM177A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM177A1 were set to PMID: 38767059, 25558065
Phenotypes for gene: FAM177A1 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: FAM177A1 was set to GREEN
gene: FAM177A1 was marked as current diagnostic
Added comment: PMID: 38767059
5 individuals from 3 unrelated families reported with with biallelic loss of function variants in FAM177A1. Clinical features included: global developmental delay, intellectual disability, seizures, behavioural abnormalities, hypotonia, gait disturbance, and macrocephaly.

They showed that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation.

PMID: 25558065
A study of 143 multiplex consanguineous families identified a homozygous frameshift variant in FAM177A1 in 1 family with 4 affected siblings with intellectual disability, dolicocephaly, obesity, and macrocephaly. The variant segregated with all 4 affected siblings and parents were confirmed heterozygous carriers.
Sources: Literature
Mendeliome v1.1813 ERF Chirag Patel reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38824261; Phenotypes: Noonan syndrome-like with or without craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.1813 SLC6A1 Sangavi Sivagnanasundram reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38781976; Phenotypes: myoclonic-atonic epilepsy MONDO:0014633; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.277 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.277 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.276 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Skeletal dysplasia v0.276 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.220 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Skeletal dysplasia v0.275 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.14 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.14 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.13 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Ciliopathies v1.53 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Ciliopathies v1.53 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Fetal anomalies v1.246 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Fetal anomalies v1.246 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Fetal anomalies v1.245 FUZ Chirag Patel reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38702430, 29068549, 34719684; Phenotypes: Ciliopathy_MONDO_0005308, skeletal ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Ciliopathies v1.52 FUZ Chirag Patel gene: FUZ was added
gene: FUZ was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684
Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy
Review for gene: FUZ was set to GREEN
gene: FUZ was marked as current diagnostic
Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Sources: Literature
Genetic Epilepsy v1.11 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1813 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Mendeliome v1.1813 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Marked gene: ANO4 as ready
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1812 ANO4 Ain Roesley Marked gene: ANO4 as ready
Mendeliome v1.1812 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1812 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Mendeliome v1.1812 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1811 FUZ Chirag Patel reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38702430, 29068549, 34719684; Phenotypes: Ciliopathy_MONDO_0005308, skeletal ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1811 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Mendeliome v1.1811 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Mendeliome v1.1810 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6030 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Genetic Epilepsy v1.10 KCND1 Ain Roesley Marked gene: KCND1 as ready
Genetic Epilepsy v1.10 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.10 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Genetic Epilepsy v1.10 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Marked gene: KCND1 as ready
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Mendeliome v1.1809 KCND1 Ain Roesley Marked gene: KCND1 as ready
Mendeliome v1.1809 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Mendeliome v1.1809 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Mendeliome v1.1809 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.9 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCND1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KCND1 were set to 38772379
Phenotypes for gene: KCND1 were set to neurodevelopmental disorder MONDO:0700092, KCND1-related
Review for gene: KCND1 was set to GREEN
gene: KCND1 was marked as current diagnostic
Added comment: 18 males from 17 families
2x de novo missense + 3x maternal NMDs + 12x maternal missense
Some functional studies were done

14x ID
4x delayed motor dev
7x muscular hypotonia
6x epilepsy
Sources: Literature
Mendeliome v1.1808 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCND1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KCND1 were set to 38772379
Phenotypes for gene: KCND1 were set to neurodevelopmental disorder MONDO:0700092, KCND1-related
Review for gene: KCND1 was set to GREEN
gene: KCND1 was marked as current diagnostic
Added comment: 18 males from 17 families
2x de novo missense + 3x maternal NMDs + 12x maternal missense
Some functional studies were done

14x ID
4x delayed motor dev
7x muscular hypotonia
6x epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6027 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCND1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KCND1 were set to 38772379
Phenotypes for gene: KCND1 were set to neurodevelopmental disorder MONDO:0700092, KCND1-related
Review for gene: KCND1 was set to GREEN
gene: KCND1 was marked as current diagnostic
Added comment: 18 males from 17 families
2x de novo missense + 3x maternal NMDs + 12x maternal missense
Some functional studies were done

14x ID
4x delayed motor dev
7x muscular hypotonia
6x epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Classified gene: ATXN7L3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6025 ATXN7L3 Chirag Patel gene: ATXN7L3 was added
gene: ATXN7L3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN7L3 were set to PMID: 38753057
Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: ATXN7L3 was set to GREEN
gene: ATXN7L3 was marked as current diagnostic
Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities.

A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality.

Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6022 FAM177A1 Chirag Patel gene: FAM177A1 was added
gene: FAM177A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FAM177A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM177A1 were set to PMID: 38767059, 25558065
Phenotypes for gene: FAM177A1 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: FAM177A1 was set to GREEN
gene: FAM177A1 was marked as current diagnostic
Added comment: PMID: 38767059
5 individuals from 3 unrelated families reported with with biallelic loss of function variants in FAM177A1. Clinical features included: global developmental delay, intellectual disability, seizures, behavioural abnormalities, hypotonia, gait disturbance, and macrocephaly.

They showed that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation.

PMID: 25558065
A study of 143 multiplex consanguineous families identified a homozygous frameshift variant in FAM177A1 in 1 family with 4 affected siblings with intellectual disability, dolicocephaly, obesity, and macrocephaly. The variant segregated with all 4 affected siblings and parents were confirmed heterozygous carriers.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Classified gene: ERF as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Gene: erf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6020 ERF Chirag Patel reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38824261; Phenotypes: Noonan syndrome-like with or without craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Rasopathy v0.104 ERF Chirag Patel Classified gene: ERF as Green List (high evidence)
Rasopathy v0.104 ERF Chirag Patel Gene: erf has been classified as Green List (High Evidence).
Rasopathy v0.103 ERF Chirag Patel gene: ERF was added
gene: ERF was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERF were set to PMID: 38824261
Phenotypes for gene: ERF were set to Noonan syndrome-like with or without craniosynostosis
Review for gene: ERF was set to GREEN
gene: ERF was marked as current diagnostic
Added comment: ERF gene encodes a transcriptional regulator negatively controlling RAS-MAPK signalling. It has been associated with syndromic craniosynostosis involving various cranial sutures and Chitayat syndrome (respiratory distress, skeletal anomalies, and facial dysmorphism).

This paper describes 26 individuals from 15 unrelated families with Noonan-syndrome (NS) like phenotype and heterozygous nonsense and frameshift variants in ERF (most cases were familial). The clinical features included: variable global developmental and/or language delay, absolute/relative macrocephaly, short stature (<3rd centile), and dysmorphism (high forehead, hypertelorism, ptosis, wide nasal bridge, and low-set/posteriorly angulated ears). There were no individuals with typical NS cardiac involvement. Craniosynostosis was only seen in 3/26 unrelated individuals.

These findings provide evidence that heterozygous loss-of-function variants in ERF cause a "RASopathy" resembling NS with or without craniosynostosis.
Sources: Literature
Hydrops fetalis v0.311 RAPSN Lilian Downie reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34302381, PMID: 33897756, PMID: 28495245; Phenotypes: Fetal akinesia deformation sequence 2 MIM#618388; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6020 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Intellectual disability syndromic and non-syndromic v0.6019 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Mendeliome v1.1807 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Mendeliome v1.1806 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Genetic Epilepsy v1.8 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 38723631
Genetic Epilepsy v1.7 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Genetic Epilepsy v1.6 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Mendeliome v1.1806 LRRC23 Zornitza Stark Phenotypes for gene: LRRC23 were changed from Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related to Spermatogenic failure 92, MIM# 620848
Mendeliome v1.1805 LRRC23 Zornitza Stark Publications for gene: LRRC23 were set to 37804054
Mendeliome v1.1804 LRRC23 Zornitza Stark Classified gene: LRRC23 as Amber List (moderate evidence)
Mendeliome v1.1804 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1803 LRRC23 Zornitza Stark reviewed gene: LRRC23: Rating: AMBER; Mode of pathogenicity: None; Publications: 38091523; Phenotypes: Spermatogenic failure 92, MIM# 620848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.47 GCSH Sangavi Sivagnanasundram gene: GCSH was added
gene: GCSH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCSH were set to 33890291; 36190515; 33569080
Phenotypes for gene: GCSH were set to glycine encephalopathy MONDO:0011612
Review for gene: GCSH was set to GREEN
Added comment: Classified Strong by ClinGen Aminoacidopathy GCEP on 10/02/2023 - https://search.clinicalgenome.org/CCID:004937

Reported in 7 individuals with abnormal biochemical metabolism.
Sources: ClinGen
Aminoacidopathy v1.47 GCDH Sangavi Sivagnanasundram edited their review of gene: GCDH: Changed rating: GREEN
Aminoacidopathy v1.47 GCH1 Sangavi Sivagnanasundram gene: GCH1 was added
gene: GCH1 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GCH1 were set to 20301681, 9749603, 10582612, 11026444, 15303002
Phenotypes for gene: GCH1 were set to GTP cyclohydrolase I deficiency MONDO:0100184
Review for gene: GCH1 was set to GREEN
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 11/12/2020 - https://search.clinicalgenome.org/CCID:004935

AD individuals have less than 50% GTPCH activity suggesting a dominant negative mechanism of disease.

AR individuals are shown to have severe deficiency of GTPCH activity resulting in hhyperphenylalaninemia due to secondary PAH deficiency which can be detected on NBS.
Sources: ClinGen
Aminoacidopathy v1.47 GCDH Sangavi Sivagnanasundram gene: GCDH was added
gene: GCDH was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 31536184, 7795610, 27476540, 31062211
Phenotypes for gene: GCDH were set to glutaryl-CoA dehydrogenase deficiency MONDO:0009281
Added comment: Classified Definitive by ClinGen Aminoacidopathy GCEP on 08/11/2019 - https://search.clinicalgenome.org/CCID:004934

Well established gene-disease association.
Affected individuals present with abnormal glutaric acid, 3-hydroxy-glutaric acid, glutaconic acid and glutarylcarnitine.
c.91+5G>T has been reported to segregate closely within closely related Native American kindreds.
Sources: ClinGen
Combined Immunodeficiency v1.65 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Immunodeficiency 120, MIM# 620836; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability
Combined Immunodeficiency v1.64 POLD1 Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Immunodeficiency 120, MIM# 620836, Low CD4 T cells, Low B cells, normal maturation, recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability
Mendeliome v1.1803 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Combined immunodeficiency, MONDO:0015131, POLD1-related to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Immunodeficiency 120, MIM# 620836
Mendeliome v1.1802 POLD1 Zornitza Stark edited their review of gene: POLD1: Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157, Immunodeficiency 120, MIM# 620836
Common Variable Immunodeficiency v1.12 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Combined Immunodeficiency v1.64 ICOSLG Zornitza Stark Phenotypes for gene: ICOSLG were changed from Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia to Immunodeficiency 119, MIM# 620825; Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia
Combined Immunodeficiency v1.63 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Mendeliome v1.1802 ICOSLG Zornitza Stark Phenotypes for gene: ICOSLG were changed from Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia to Immunodeficiency 119, MIM# 620825; Combined immunodeficiency; recurrent bacterial and viral infections; neutropaenia
Mendeliome v1.1801 ICOSLG Zornitza Stark edited their review of gene: ICOSLG: Changed phenotypes: Immunodeficiency 119, MIM# 620825, Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.326 SYCP2L Zornitza Stark Phenotypes for gene: SYCP2L were changed from Premature ovarian insufficiency to Premature ovarian failure 24, MIM# 620840
Mendeliome v1.1801 SYCP2L Zornitza Stark Phenotypes for gene: SYCP2L were changed from Premature ovarian insufficiency to Premature ovarian failure 24, MIM# 620840
Cerebral Palsy v1.275 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Cerebral Palsy v1.275 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.275 DLG4 Zornitza Stark Classified gene: DLG4 as Red List (low evidence)
Cerebral Palsy v1.275 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.274 DLG4 Zornitza Stark Classified gene: DLG4 as Red List (low evidence)
Cerebral Palsy v1.274 DLG4 Zornitza Stark Gene: dlg4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.273 DCC Zornitza Stark Marked gene: DCC as ready
Cerebral Palsy v1.273 DCC Zornitza Stark Gene: dcc has been classified as Red List (Low Evidence).
Cerebral Palsy v1.273 DCC Zornitza Stark Classified gene: DCC as Red List (low evidence)
Cerebral Palsy v1.273 DCC Zornitza Stark Gene: dcc has been classified as Red List (Low Evidence).
Cerebral Palsy v1.272 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Cerebral Palsy v1.272 CUL3 Zornitza Stark Gene: cul3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.272 CUL3 Zornitza Stark Classified gene: CUL3 as Red List (low evidence)
Cerebral Palsy v1.272 CUL3 Zornitza Stark Gene: cul3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Marked gene: DNMT3A as ready
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Classified gene: DNMT3A as Red List (low evidence)
Cerebral Palsy v1.271 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Classified gene: EHMT1 as Red List (low evidence)
Cerebral Palsy v1.270 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.269 EZH2 Zornitza Stark Marked gene: EZH2 as ready
Cerebral Palsy v1.269 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.269 EZH2 Zornitza Stark Classified gene: EZH2 as Red List (low evidence)
Cerebral Palsy v1.269 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Classified gene: FGFR1 as Red List (low evidence)
Cerebral Palsy v1.268 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.267 FUS Zornitza Stark Marked gene: FUS as ready
Cerebral Palsy v1.267 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Cerebral Palsy v1.267 FUS Zornitza Stark Classified gene: FUS as Red List (low evidence)
Cerebral Palsy v1.267 FUS Zornitza Stark Gene: fus has been classified as Red List (Low Evidence).
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Marked gene: GABBR2 as ready
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Classified gene: GABBR2 as Red List (low evidence)
Cerebral Palsy v1.266 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Classified gene: GATAD2B as Red List (low evidence)
Cerebral Palsy v1.265 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Marked gene: GRIN2A as ready
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Gene: grin2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Classified gene: GRIN2A as Red List (low evidence)
Cerebral Palsy v1.264 GRIN2A Zornitza Stark Gene: grin2a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Marked gene: HIVEP2 as ready
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Classified gene: HIVEP2 as Red List (low evidence)
Cerebral Palsy v1.263 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.262 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Cerebral Palsy v1.262 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.262 KAT6B Zornitza Stark Classified gene: KAT6B as Red List (low evidence)
Cerebral Palsy v1.262 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Marked gene: KCNH1 as ready
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Classified gene: KCNH1 as Red List (low evidence)
Cerebral Palsy v1.261 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Marked gene: KCNQ3 as ready
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Classified gene: KCNQ3 as Red List (low evidence)
Cerebral Palsy v1.260 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Marked gene: KCNQ5 as ready
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Classified gene: KCNQ5 as Red List (low evidence)
Cerebral Palsy v1.259 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.258 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Cerebral Palsy v1.258 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.258 KMT2D Zornitza Stark Classified gene: KMT2D as Red List (low evidence)
Cerebral Palsy v1.258 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.257 MACF1 Zornitza Stark Marked gene: MACF1 as ready
Cerebral Palsy v1.257 MACF1 Zornitza Stark Gene: macf1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.257 MACF1 Zornitza Stark Classified gene: MACF1 as Red List (low evidence)
Cerebral Palsy v1.257 MACF1 Zornitza Stark Gene: macf1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.256 MBD5 Zornitza Stark Marked gene: MBD5 as ready
Cerebral Palsy v1.256 MBD5 Zornitza Stark Gene: mbd5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.256 MBD5 Zornitza Stark Classified gene: MBD5 as Red List (low evidence)
Cerebral Palsy v1.256 MBD5 Zornitza Stark Gene: mbd5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.255 MED13L Zornitza Stark Marked gene: MED13L as ready
Cerebral Palsy v1.255 MED13L Zornitza Stark Gene: med13l has been classified as Red List (Low Evidence).
Cerebral Palsy v1.255 MED13L Zornitza Stark Classified gene: MED13L as Red List (low evidence)
Cerebral Palsy v1.255 MED13L Zornitza Stark Gene: med13l has been classified as Red List (Low Evidence).
Cerebral Palsy v1.254 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Cerebral Palsy v1.254 MYH2 Zornitza Stark Gene: myh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.254 MYH2 Zornitza Stark Classified gene: MYH2 as Red List (low evidence)
Cerebral Palsy v1.254 MYH2 Zornitza Stark Gene: myh2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.253 NEFL Zornitza Stark Marked gene: NEFL as ready
Cerebral Palsy v1.253 NEFL Zornitza Stark Gene: nefl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.253 NEFL Zornitza Stark Classified gene: NEFL as Red List (low evidence)
Cerebral Palsy v1.253 NEFL Zornitza Stark Gene: nefl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Red List (low evidence)
Cerebral Palsy v1.252 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.251 NFIB Zornitza Stark Marked gene: NFIB as ready
Cerebral Palsy v1.251 NFIB Zornitza Stark Gene: nfib has been classified as Red List (Low Evidence).
Cerebral Palsy v1.251 NFIB Zornitza Stark Classified gene: NFIB as Red List (low evidence)
Cerebral Palsy v1.251 NFIB Zornitza Stark Gene: nfib has been classified as Red List (Low Evidence).
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Marked gene: NOTCH1 as ready
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Classified gene: NOTCH1 as Red List (low evidence)
Cerebral Palsy v1.250 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Classified gene: NR2F1 as Red List (low evidence)
Cerebral Palsy v1.249 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.248 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Cerebral Palsy v1.248 NSD1 Zornitza Stark Gene: nsd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.248 NSD1 Zornitza Stark Classified gene: NSD1 as Red List (low evidence)
Cerebral Palsy v1.248 NSD1 Zornitza Stark Gene: nsd1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.247 NSD2 Zornitza Stark Marked gene: NSD2 as ready
Cerebral Palsy v1.247 NSD2 Zornitza Stark Gene: nsd2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.247 NSD2 Zornitza Stark Classified gene: NSD2 as Red List (low evidence)
Cerebral Palsy v1.247 NSD2 Zornitza Stark Gene: nsd2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.246 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Cerebral Palsy v1.246 PACS1 Zornitza Stark Gene: pacs1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.246 PACS1 Zornitza Stark Classified gene: PACS1 as Red List (low evidence)
Cerebral Palsy v1.246 PACS1 Zornitza Stark Gene: pacs1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.245 PHIP Zornitza Stark Marked gene: PHIP as ready
Cerebral Palsy v1.245 PHIP Zornitza Stark Gene: phip has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.245 PHIP Zornitza Stark Classified gene: PHIP as Amber List (moderate evidence)
Cerebral Palsy v1.245 PHIP Zornitza Stark Gene: phip has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.244 PPM1D Zornitza Stark Marked gene: PPM1D as ready
Cerebral Palsy v1.244 PPM1D Zornitza Stark Gene: ppm1d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.244 PPM1D Zornitza Stark Classified gene: PPM1D as Red List (low evidence)
Cerebral Palsy v1.244 PPM1D Zornitza Stark Gene: ppm1d has been classified as Red List (Low Evidence).
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Classified gene: SETBP1 as Red List (low evidence)
Cerebral Palsy v1.243 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.242 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Cerebral Palsy v1.242 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.242 SETD2 Zornitza Stark Classified gene: SETD2 as Amber List (moderate evidence)
Cerebral Palsy v1.242 SETD2 Zornitza Stark Gene: setd2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.241 SGCE Zornitza Stark Marked gene: SGCE as ready
Cerebral Palsy v1.241 SGCE Zornitza Stark Gene: sgce has been classified as Red List (Low Evidence).
Cerebral Palsy v1.241 SGCE Zornitza Stark Classified gene: SGCE as Red List (low evidence)
Cerebral Palsy v1.241 SGCE Zornitza Stark Gene: sgce has been classified as Red List (Low Evidence).
Cerebral Palsy v1.240 SIK1 Zornitza Stark Marked gene: SIK1 as ready
Cerebral Palsy v1.240 SIK1 Zornitza Stark Gene: sik1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.240 SIK1 Zornitza Stark Classified gene: SIK1 as Red List (low evidence)
Cerebral Palsy v1.240 SIK1 Zornitza Stark Gene: sik1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Amber List (moderate evidence)
Cerebral Palsy v1.239 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Marked gene: SLC6A5 as ready
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Classified gene: SLC6A5 as Red List (low evidence)
Cerebral Palsy v1.238 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Classified gene: SMARCA2 as Red List (low evidence)
Cerebral Palsy v1.237 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Red List (low evidence)
Cerebral Palsy v1.236 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.235 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Cerebral Palsy v1.235 SMC3 Zornitza Stark Gene: smc3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.235 SMC3 Zornitza Stark Classified gene: SMC3 as Red List (low evidence)
Cerebral Palsy v1.235 SMC3 Zornitza Stark Gene: smc3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.234 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Cerebral Palsy v1.234 SOX10 Zornitza Stark Gene: sox10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.234 SOX10 Zornitza Stark Classified gene: SOX10 as Red List (low evidence)
Cerebral Palsy v1.234 SOX10 Zornitza Stark Gene: sox10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.233 TANC2 Zornitza Stark Marked gene: TANC2 as ready
Cerebral Palsy v1.233 TANC2 Zornitza Stark Gene: tanc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.233 TANC2 Zornitza Stark Classified gene: TANC2 as Red List (low evidence)
Cerebral Palsy v1.233 TANC2 Zornitza Stark Gene: tanc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.232 TBR1 Zornitza Stark Marked gene: TBR1 as ready
Cerebral Palsy v1.232 TBR1 Zornitza Stark Gene: tbr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.232 TBR1 Zornitza Stark Classified gene: TBR1 as Red List (low evidence)
Cerebral Palsy v1.232 TBR1 Zornitza Stark Gene: tbr1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.231 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Cerebral Palsy v1.231 TBX6 Zornitza Stark Gene: tbx6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.231 TBX6 Zornitza Stark Classified gene: TBX6 as Red List (low evidence)
Cerebral Palsy v1.231 TBX6 Zornitza Stark Gene: tbx6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.230 TGM6 Zornitza Stark Marked gene: TGM6 as ready
Cerebral Palsy v1.230 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.230 TGM6 Zornitza Stark Classified gene: TGM6 as Red List (low evidence)
Cerebral Palsy v1.230 TGM6 Zornitza Stark Gene: tgm6 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.229 TOR1A Zornitza Stark Marked gene: TOR1A as ready
Cerebral Palsy v1.229 TOR1A Zornitza Stark Gene: tor1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.229 TOR1A Zornitza Stark Classified gene: TOR1A as Red List (low evidence)
Cerebral Palsy v1.229 TOR1A Zornitza Stark Gene: tor1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.228 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Cerebral Palsy v1.228 TSC2 Zornitza Stark Gene: tsc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.228 TSC2 Zornitza Stark Classified gene: TSC2 as Red List (low evidence)
Cerebral Palsy v1.228 TSC2 Zornitza Stark Gene: tsc2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.227 TSHR Zornitza Stark Marked gene: TSHR as ready
Cerebral Palsy v1.227 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.227 TSHR Zornitza Stark Classified gene: TSHR as Red List (low evidence)
Cerebral Palsy v1.227 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Prepair 1000+ v1.6 AAAS Zornitza Stark edited their review of gene: AAAS: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.6 AAAS Zornitza Stark edited their review of gene: AAAS: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.6 AAAS Zornitza Stark reviewed gene: AAAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Achalasia-addisonianism-alacrimia syndrome, MIM# 231550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Marked gene: SSR4 as ready
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Phenotypes for gene: SSR4 were changed from to Congenital disorder of glycosylation, type Iy, MIM# 300934
Intellectual disability syndromic and non-syndromic v0.6018 SSR4 Zornitza Stark Publications for gene: SSR4 were set to
Intellectual disability syndromic and non-syndromic v0.6017 SSR4 Zornitza Stark Mode of inheritance for gene: SSR4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 SSR4 Zornitza Stark reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Iy, MIM# 300934; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Marked gene: RELN as ready
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Gene: reln has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Publications for gene: RELN were set to
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 2 (Norman-Roberts type), MIM# 257320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark Phenotypes for gene: RELN were changed from to Lissencephaly 2 (Norman-Roberts type), MIM# 257320
Intellectual disability syndromic and non-syndromic v0.6014 RELN Zornitza Stark Mode of inheritance for gene: RELN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6013 SLC35A1 Anissa Johnson Deleted their review
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller changed review comment from: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin”lisencephaly pachygyria with cerebellar hypoplasia
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).; to: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin” lisencephaly pachygyria with cerebellar hypoplasia.
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller edited their review of gene: RELN: Changed publications: PMID: 35769015, PMID: 29671837
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35769015, 29671837; Phenotypes: OMIM *600514, HP:0001339, DOID:0070338; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.226 CTCF Zornitza Stark Marked gene: CTCF as ready
Cerebral Palsy v1.226 CTCF Zornitza Stark Gene: ctcf has been classified as Red List (Low Evidence).
Cerebral Palsy v1.226 CTCF Zornitza Stark Classified gene: CTCF as Red List (low evidence)
Cerebral Palsy v1.226 CTCF Zornitza Stark Gene: ctcf has been classified as Red List (Low Evidence).
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Marked gene: CLCN7 as ready
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Classified gene: CLCN7 as Red List (low evidence)
Cerebral Palsy v1.225 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.224 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Cerebral Palsy v1.224 CHD7 Zornitza Stark Gene: chd7 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.224 CHD7 Zornitza Stark Classified gene: CHD7 as Amber List (moderate evidence)
Cerebral Palsy v1.224 CHD7 Zornitza Stark Gene: chd7 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.223 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Cerebral Palsy v1.223 CHD4 Zornitza Stark Gene: chd4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.223 CHD4 Zornitza Stark Classified gene: CHD4 as Red List (low evidence)
Cerebral Palsy v1.223 CHD4 Zornitza Stark Gene: chd4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Marked gene: CHCHD10 as ready
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Classified gene: CHCHD10 as Red List (low evidence)
Cerebral Palsy v1.222 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Marked gene: CAMK2G as ready
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Gene: camk2g has been classified as Red List (Low Evidence).
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Classified gene: CAMK2G as Red List (low evidence)
Cerebral Palsy v1.221 CAMK2G Zornitza Stark Gene: camk2g has been classified as Red List (Low Evidence).
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Marked gene: CAMK2B as ready
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Gene: camk2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Classified gene: CAMK2B as Red List (low evidence)
Cerebral Palsy v1.220 CAMK2B Zornitza Stark Gene: camk2b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Marked gene: CACNA1G as ready
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Classified gene: CACNA1G as Green List (high evidence)
Cerebral Palsy v1.219 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Marked gene: CACNA1D as ready
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Classified gene: CACNA1D as Amber List (moderate evidence)
Cerebral Palsy v1.218 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Marked gene: ATP6V1A as ready
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Classified gene: ATP6V1A as Red List (low evidence)
Cerebral Palsy v1.217 ATP6V1A Zornitza Stark Gene: atp6v1a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Classified gene: ATP1A2 as Red List (low evidence)
Cerebral Palsy v1.216 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.215 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Cerebral Palsy v1.215 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.215 ARID1B Zornitza Stark Classified gene: ARID1B as Red List (low evidence)
Cerebral Palsy v1.215 ARID1B Zornitza Stark Gene: arid1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.214 DNM2 Zornitza Stark Marked gene: DNM2 as ready
Cerebral Palsy v1.214 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.214 DNM2 Zornitza Stark Classified gene: DNM2 as Red List (low evidence)
Cerebral Palsy v1.214 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.213 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to 34531397; 33528536
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Marked gene: TUBG1 as ready
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Classified gene: TUBG1 as Red List (low evidence)
Cerebral Palsy v1.212 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.211 UBE3A Zornitza Stark Publications for gene: UBE3A were set to PMID: 33528536
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Classified gene: ZBTB18 as Red List (low evidence)
Cerebral Palsy v1.210 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.209 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to 33528536; 33098801
Cerebral Palsy v1.208 ITPR1 Zornitza Stark Publications for gene: ITPR1 were set to 28826917; 25981959; 22986007
Cerebral Palsy v1.207 SPTBN2 Zornitza Stark Publications for gene: SPTBN2 were set to 31066025; 25981959; 31721007
Cerebral Palsy v1.206 AP4M1 Zornitza Stark Publications for gene: AP4M1 were set to 19559397; 24065543; 25496299
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Gene: acad9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Classified gene: ACAD9 as Red List (low evidence)
Cerebral Palsy v1.205 ACAD9 Zornitza Stark Gene: acad9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Gene: armc9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Classified gene: ARMC9 as Red List (low evidence)
Cerebral Palsy v1.204 ARMC9 Zornitza Stark Gene: armc9 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.203 ARSA Zornitza Stark Marked gene: ARSA as ready
Cerebral Palsy v1.203 ARSA Zornitza Stark Gene: arsa has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.203 ARSA Zornitza Stark Classified gene: ARSA as Amber List (moderate evidence)
Cerebral Palsy v1.203 ARSA Zornitza Stark Gene: arsa has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.202 ASL Zornitza Stark Marked gene: ASL as ready
Cerebral Palsy v1.202 ASL Zornitza Stark Gene: asl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.202 ASL Zornitza Stark Classified gene: ASL as Red List (low evidence)
Cerebral Palsy v1.202 ASL Zornitza Stark Gene: asl has been classified as Red List (Low Evidence).
Cerebral Palsy v1.201 ASPA Zornitza Stark Marked gene: ASPA as ready
Cerebral Palsy v1.201 ASPA Zornitza Stark Gene: aspa has been classified as Red List (Low Evidence).
Cerebral Palsy v1.201 ASPA Zornitza Stark Classified gene: ASPA as Red List (low evidence)
Cerebral Palsy v1.201 ASPA Zornitza Stark Gene: aspa has been classified as Red List (Low Evidence).
Cerebral Palsy v1.200 ATR Zornitza Stark Marked gene: ATR as ready
Cerebral Palsy v1.200 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.200 ATR Zornitza Stark Classified gene: ATR as Red List (low evidence)
Cerebral Palsy v1.200 ATR Zornitza Stark Gene: atr has been classified as Red List (Low Evidence).
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Marked gene: B4GALNT1 as ready
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Classified gene: B4GALNT1 as Red List (low evidence)
Cerebral Palsy v1.199 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Marked gene: CACNA1B as ready
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Classified gene: CACNA1B as Red List (low evidence)
Cerebral Palsy v1.198 CACNA1B Zornitza Stark Gene: cacna1b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Marked gene: DPYD as ready
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Phenotypes for gene: DPYD were changed from to Dihydropyrimidine dehydrogenase deficiency (MIM#274270)
Intellectual disability syndromic and non-syndromic v0.6012 DPYD Zornitza Stark Publications for gene: DPYD were set to
Intellectual disability syndromic and non-syndromic v0.6011 DPYD Zornitza Stark Mode of inheritance for gene: DPYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Classified gene: DPYD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Marked gene: DMD as ready
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Phenotypes for gene: DMD were changed from to Duchenne muscular dystrophy MIM#310200
Intellectual disability syndromic and non-syndromic v0.6008 DMD Zornitza Stark Mode of inheritance for gene: DMD was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 SSR4 Katie Thompson changed review comment from: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein; to: Decipher - disorder of glycosolation (XLR), strong evidence
ORPHA:370927 GenCC strong. Not in gene2phenotype.
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein. All variants caused loss of function mainly from premature termination.
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Marked gene: COG7 as ready
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Gene: cog7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Phenotypes for gene: COG7 were changed from to Congenital disorder of glycosylation, type IIe , MIM#608779
Intellectual disability syndromic and non-syndromic v0.6006 COG7 Zornitza Stark Publications for gene: COG7 were set to
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 COG7 Zornitza Stark reviewed gene: COG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 15107842, 17356545, 28883096; Phenotypes: Congenital disorder of glycosylation, type IIe , MIM#608779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 SSR4 Katie Thompson changed review comment from: PMID: 24218363; 26264460
SSR4
Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females; to: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Marked gene: COG1 as ready
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Gene: cog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Phenotypes for gene: COG1 were changed from to Congenital disorder of glycosylation, type IIg, MIM# 611209
Intellectual disability syndromic and non-syndromic v0.6003 COG1 Zornitza Stark Publications for gene: COG1 were set to
Intellectual disability syndromic and non-syndromic v0.6002 COG1 Zornitza Stark Mode of inheritance for gene: COG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 SSR4 Katie Thompson reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24218363, 26264460; Phenotypes: intellectual disabilities, hypotonia, microcephaly, seizures, Feeding problems, Facial dysmorphism, Gastrointestinal abnormalities, Failure to thrive, strabismus; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6001 COG1 Zornitza Stark reviewed gene: COG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16537452, 19008299, 17904886, 11980916; Phenotypes: Congenital disorder of glycosylation, type IIg, MIM# 611209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from to COL4A1-related disorder MONDO:0800461
Intellectual disability syndromic and non-syndromic v0.6000 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Intellectual disability syndromic and non-syndromic v0.5999 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528)
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5996 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5995 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.6 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Neurodevelopmental disorder MONDO:0700092, GABRA4-related to Neurodevelopmental disorder MONDO:0700092, GABRA4-related