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05 Apr 2022	Rare genetic inflammatory skin disorders v1.54	GJB4	Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'both monoallelic and biallelic' to just 'monoallelic' as the literature only reports heterozygous (monoallelic) variants associated with EKVP. Rare biallelic forms of EKVP have so far only been reported for GJB3 (OMIM:133200).
05 Apr 2022	Rare genetic inflammatory skin disorders v1.54	GJB4	Arina Puzriakova Mode of inheritance for gene: GJB4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
05 Apr 2022	Rare genetic inflammatory skin disorders v1.53	GJB4	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: GJB4.
05 Apr 2022	Pigmentary skin disorders v1.50	GJB4	Arina Puzriakova Phenotypes for gene: GJB4 were changed from Erythrokeratodermia variabilis; EKVP2; ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 2 to Erythrokeratodermia variabilis et progressiva 2, OMIM:617524
05 Apr 2022	Palmoplantar keratoderma and erythrokeratodermas v1.24	GJB4	Arina Puzriakova Phenotypes for gene: GJB4 were changed from Erythrokeratodermia variabilis et progressiva 2, 617524 to Erythrokeratodermia variabilis et progressiva 2, OMIM:617524
05 Apr 2022	Intellectual disability v3.1538	GDAP1	Arina Puzriakova Mode of inheritance for gene: GDAP1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
05 Apr 2022	Hereditary neuropathy or pain disorder v1.92	GDAP1	Arina Puzriakova Mode of inheritance for gene: GDAP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
05 Apr 2022	Hereditary neuropathy v1.446	GDAP1	Arina Puzriakova Mode of inheritance for gene: GDAP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
05 Apr 2022	Possible mitochondrial disorder - nuclear genes v1.72	GDAP1	Arina Puzriakova Mode of inheritance for gene: GDAP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
05 Apr 2022	Hereditary neuropathy or pain disorder v1.91	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease, recessive intermediate, A, 608340; Charcot-Marie-Tooth with Vocal Cord Paresis (recessive); Charcot Marie Tooth disease, type 4A, 214400; Charcot Marie Tooth disease, axonal, type 2K, 607831; Charcot-Marie-Tooth, Intermediate (Dominant) to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Intellectual disability v3.1537	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot-Marie-Tooth disease, type 4A, 214400; Charcot-Marie-Tooth; disease, axonal, with vocal cord paresis, 607706; Charcot-Marie-Tooth disease, axonal, type 2K, 607831; Charcot-Marie-Tooth disease, recessive; intermediate, A, 608340 to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Mitochondrial disorders v2.97	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, axonal, type 2K; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, type 4A to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Hereditary neuropathy v1.445	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease, axonal, type 2K, 607831; Charcot Marie Tooth disease, type 4A, 214400; Charcot-Marie-Tooth, Intermediate (Dominant); Charcot Marie Tooth disease, type 4A, 214400; Charcot Marie Tooth disease, recessive intermediate, A, 608340; Charcot Marie Tooth disease, axonal, type 2K, 607831; Charcot-Marie-Tooth, Intermediate (Dominant); Charcot-Marie-Tooth with Vocal Cord Paresis (recessive); Charcot Marie Tooth disease, recessive intermediate, A, 608340 to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Likely inborn error of metabolism v2.240	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, type 4A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, type 2K to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Possible mitochondrial disorder - nuclear genes v1.71	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot-Marie-Tooth disease, axonal, type 2K, 607831; Charcot-Marie-Tooth disease, recessive intermediate, A, 608340; Charcot-Marie-Tooth disease, type 4A, 214400; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, 607706 to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Undiagnosed metabolic disorders v1.522	GDAP1	Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, axonal, type 2K; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, type 4A to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400
05 Apr 2022	Adult solid tumours cancer susceptibility v2.19	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Lynch syndrome to Colorectal cancer, hereditary nonpolyposis, type 8, OMIM:613244
05 Apr 2022	GI tract tumours v1.19	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Gastrointestinal and Colorectal Cancer; High Risk Colorectal Cancer to Colorectal cancer, hereditary nonpolyposis, type 8, OMIM:613244
05 Apr 2022	Adult solid tumours for rare disease v1.32	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Lynch syndrome to Colorectal cancer, hereditary nonpolyposis, type 8, OMIM:613244
05 Apr 2022	COVID-19 research v1.122	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Diarrhea 5, with tufting enteropathy, congenital to Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217
05 Apr 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.542	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Diarrhea 5, with tufting enteropathy, congenital to Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217
05 Apr 2022	Gastrointestinal epithelial barrier disorders v1.72	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Diarrhea 5, with tufting enteropathy, congenital 613217; Diarrhea 5, with tufting enteropathy, congenital; Colorectal cancer, hereditary nonpolyposis, type 8, 613244; Diarrhea 5, with tufting enteropathy, congenital, 613217 to Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217
05 Apr 2022	Infantile enterocolitis & monogenic inflammatory bowel disease v1.38	EPCAM	Arina Puzriakova Phenotypes for gene: EPCAM were changed from Diarrhea 5, with tufting enteropathy, congenital 613217 to Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217
05 Apr 2022	Hereditary neuropathy or pain disorder v1.90	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Dysautonomia, familial, 223900 to Dysautonomia, familial, OMIM:223900
05 Apr 2022	Hereditary neuropathy v1.444	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Dysautonomia, familial, 223900 to Dysautonomia, familial, OMIM:223900
05 Apr 2022	Paroxysmal central nervous system disorders v1.44	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Neuropathy, Hereditary Sensory and Autonomic, Type III; Familial dysautonomia; Dysautonomia, familial, 223900 to Dysautonomia, familial, OMIM:223900
05 Apr 2022	Pain syndromes v1.12	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Familial dysautonomia; NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; Dysautonomia, familial, 223900 to Dysautonomia, familial, OMIM:223900
05 Apr 2022	Familial dysautonomia v1.17	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Familial Dysautonomia; Neuropathy, hereditary sensory and autonomic, type 3; Riley-Day Syndrome 223900 to Dysautonomia, familial, OMIM:223900
05 Apr 2022	Childhood solid tumours cancer susceptibility v1.19	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Paediatric medulloblastoma Sonic Hedgehog subtype to Medulloblastoma, OMIM:155255
05 Apr 2022	Childhood solid tumours v2.31	ELP1	Arina Puzriakova Phenotypes for gene: ELP1 were changed from Medulloblastoma predisposition to Medulloblastoma, OMIM:155255
05 Apr 2022	Palmoplantar keratodermas v1.13	CDSN	Arina Puzriakova Tag Q2_22_rating tag was added to gene: CDSN. Tag Q2_22_expert_review tag was added to gene: CDSN.
05 Apr 2022	Palmoplantar keratodermas v1.13	CDSN	Arina Puzriakova commented on gene: CDSN
05 Apr 2022	Peeling skin syndrome v1.4	CDSN	Arina Puzriakova Phenotypes for gene: CDSN were changed from Peeling skin syndrome 1, 270300; PSS1; OMIM:#270300; Peeling skin HP:0040189; Pruritus HP:0000989; Allergy HP:0012393; Increased IgE level HP:0003212; Generalised erythroderma HP:0001019; erythema HP:0010783; Hyperkeratosis HP:0000962. to Peeling skin syndrome 1, OMIM:270300; Peeling skin HP:0040189; Pruritus HP:0000989; Allergy HP:0012393; Increased IgE level HP:0003212; Generalised erythroderma HP:0001019; erythema HP:0010783; Hyperkeratosis HP:0000962.
05 Apr 2022	Intellectual disability v3.1536	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Gene2Phenotype confirmed gene with ID HPO to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Fetal anomalies v1.849	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from FANCONI ANEMIA, COMPLEMENTATION GROUP J to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Confirmed Fanconi anaemia or Bloom syndrome v1.16	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from 609054 Fanconi anemia, complementation group J; Fanconi anemia, complementation group J, 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Severe microcephaly v2.296	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J, 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Haematological malignancies cancer susceptibility v2.26	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Class: BM failure FA, (typ AR); AML; leukaemia; breast; Fanconi anaemia J; breast cancer susceptiblity; MDS; Leukaemia; Bone marrow failure; Head and neck and anogenital squamous cell cancers, liver cancer, esophageal cancer, Squamous cell carcinoma oral, GI, vulvar to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Childhood solid tumours cancer susceptibility v1.18	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Cytopenias and congenital anaemias v1.103	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Pigmentary skin disorders v1.49	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from FANCJ; FANCONI ANEMIA, COMPLEMENTATION GROUP J to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Limb disorders v2.77	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Radial Ray abnormality; Fanconi anemia, complementation group J, 609054 to Fanconi anemia, complementation group J, OMIM:609054; Radial ray abnormality
05 Apr 2022	Childhood solid tumours v2.30	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J, 609054; Fanconi anemia, complementation group J, 609054; Fanconi Anaemia; ?Breast cancer, early-onset, 114480; Fanconi Anemia to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	COVID-19 research v1.121	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J, 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Neurofibromatosis Type 1 v1.29	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from ?Breast cancer, early-onset, 114480; Fanconi anemia, complementation group J, 609054; Fanconi Anemia; Fanconi Anaemia to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Haematological malignancies for rare disease v1.10	BRIP1	Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: "Class: BM failure FA, (typ AR);AML; leukaemia; breast;Fanconi anaemia J; breast cancer susceptiblity;MDS; Leukaemia;Bone marrow failure;Head and neck and anogenital squamous cell cancers, liver cancer, esophageal cancer, Squamous cell carcinoma oral, GI, vulvar"
05 Apr 2022	Haematological malignancies for rare disease v1.10	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Class: BM failure FA, (typ AR); AML; leukaemia; breast; Fanconi anaemia J; breast cancer susceptiblity; MDS; Leukaemia; Bone marrow failure; Head and neck and anogenital squamous cell cancers, liver cancer, esophageal cancer, Squamous cell carcinoma oral, GI, vulvar to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Radial dysplasia v1.18	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J, 609054 to Fanconi anemia, complementation group J, OMIM:609054
05 Apr 2022	Adult solid tumours cancer susceptibility v2.18	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from predisposition to ovarian cancer to {Breast cancer, early-onset, susceptibility to}, OMIM:114480
05 Apr 2022	Adult solid tumours for rare disease v1.31	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from predisposition to ovarian cancer to {Breast cancer, early-onset, susceptibility to}, OMIM:114480
05 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.9	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from to {Breast cancer, early-onset, susceptibility to}, OMIM:114480
05 Apr 2022	Familial breast cancer v1.18	BRIP1	Arina Puzriakova Phenotypes for gene: BRIP1 were changed from ?Breast cancer, early-onset, 114480; Fanconi anemia, complementation group J, 609054; Breast and Ovarian Cancer; Breast Cancer to {Breast cancer, early-onset, susceptibility to}, OMIM:114480
04 Apr 2022	Osteogenesis imperfecta v2.45	P4HB	Eleanor Williams Tag Q2_22_MOI tag was added to gene: P4HB.
04 Apr 2022	Osteogenesis imperfecta v2.45	P4HB	Eleanor Williams Phenotypes for gene: P4HB were changed from Cole-Carpenter Syndrome; Osteogenesis Imperfecta; Cole Carpenter syndrome to Cole-Carpenter syndrome 1, OMIM:112240; Cole-Carpenter syndrome 1, MONDO:000720
04 Apr 2022	Osteogenesis imperfecta v2.44	P4HB	Eleanor Williams Added comment: Comment on mode of inheritance: Cole-Carpenter syndrome 1 is due to heterozygous variants in P4HB and so the mode of inheritance should be changed to monoallelic at the next review.
04 Apr 2022	Osteogenesis imperfecta v2.44	P4HB	Eleanor Williams Mode of inheritance for gene: P4HB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
04 Apr 2022	Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.22	CFHR5	Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as Both mono and biallelic just now, but only monoallelic cases confirmed so recommending a change to this mode of inheritance.
04 Apr 2022	Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.22	CFHR5	Eleanor Williams Mode of inheritance for gene: CFHR5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
04 Apr 2022	Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21	CFHR5	Eleanor Williams Tag Q2_22_MOI tag was added to gene: CFHR5.
04 Apr 2022	Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.21	CFHR5	Eleanor Williams reviewed gene: CFHR5: Rating: ; Mode of pathogenicity: None; Publications: 20800271, 22503529, 23402027, 24334459, 24067434, 34566977; Phenotypes: Nephropathy due to CFHR5 deficiency, OMIM:614809; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
04 Apr 2022	Childhood solid tumours cancer susceptibility v1.17	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Hereditary Breast and Ovarian Cancer to Fanconi anemia, complementation group D1, OMIM:605724; Wilms tumor, OMIM:194070; {Glioblastoma 3}, OMIM:613029; {Medulloblastoma}, OMIM:155255
04 Apr 2022	Childhood solid tumours v2.29	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Wilms tumor, 194070; Fanconi Anaemia; {Breast cancer, male, susceptibility to}, 114480; Prostate cancer, 176807; {Medulloblastoma}, 155255; {Glioblastoma 3}, 613029; Fanconi Anemia; Hereditary Breast and Ovarian Cancer; Fanconi anemia, complementation group D1, 605724; {Breast-ovarian cancer, familial, 2}, 612555; Pancreatic cancer, 613347 to Fanconi anemia, complementation group D1, OMIM:605724; Wilms tumor, OMIM:194070; {Glioblastoma 3}, OMIM:613029; {Medulloblastoma}, OMIM:155255
04 Apr 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.541	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure; Fanconi Anemia Type D1 to Fanconi anemia, complementation group D1, OMIM:605724; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure
04 Apr 2022	COVID-19 research v1.120	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure; Fanconi Anemia Type D1 to Fanconi anemia, complementation group D1, OMIM:605724; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure
04 Apr 2022	Intellectual disability v3.1535	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1: FANCD1 OMIM: 605724 to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Confirmed Fanconi anaemia or Bloom syndrome v1.15	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from 605724 Fanconi anemia, complementation group D1; Fanconi anemia, complementation group D1, 605724 to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Severe microcephaly v2.295	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724 (Microcephaly) to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Haematological malignancies cancer susceptibility v2.25	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Class: BM failure FA, (typ AR); Fanconi anemia; breast, ovarian, pancreatic, leukaemia (FANCB, FANCD1); hereditary breast, ovarian cancer; MDS; AML, Leukaemia; Bone marrow failure; Head and neck and anogenital squamous cell cancers, liver cancer, esophageal cancer ,Squamous cell carcinoma: oral, GI, vulvar to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Cytopenias and congenital anaemias v1.102	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1 605724 to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Pigmentary skin disorders v1.48	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from FANCD1; FANCONI ANEMIA, COMPLEMENTATION GROUP D1 to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Limb disorders v2.76	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724; Radial Ray abnormality to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Neurofibromatosis Type 1 v1.28	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from {Breast-ovarian cancer, familial, 2}, 612555; Fanconi anemia, complementation group D1, 605724; Prostate cancer, 176807; {Breast cancer, male, susceptibility to}, 114480; Wilms tumor, 194070; {Medulloblastoma}, 155255; {Glioblastoma 3}, 613029; Pancreatic cancer, 613347; {Glioblastoma 3},; Fanconi Anemia; Fanconi Anaemia to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Haematological malignancies for rare disease v1.9	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Class: BM failure FA, (typ AR); Fanconi anemia; breast, ovarian, pancreatic, leukaemia (FANCB, FANCD1); hereditary breast, ovarian cancer; MDS; AML, Leukaemia; Bone marrow failure; Head and neck and anogenital squamous cell cancers, liver cancer, esophageal cancer ,Squamous cell carcinoma: oral, GI, vulvar to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Radial dysplasia v1.17	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724 to Fanconi anemia, complementation group D1, OMIM:605724
04 Apr 2022	Prostate cancer pertinent cancer susceptibility v1.2	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Prostate cancer to {Prostate cancer}, OMIM:176807
04 Apr 2022	Familial prostate cancer v1.3	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from male breast cancer and prostate cancer; {Prostate cancer} 176807 to {Prostate cancer}, OMIM:176807
04 Apr 2022	Additional findings health related - CNV analysis adult specific v1.2	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Adult only; Breast and ovarian cancer predisposition to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480; Adult only
04 Apr 2022	Additional findings health related - adult specific v1.2	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Adult only; Breast and ovarian cancer predisposition to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480; Adult only
04 Apr 2022	Adult solid tumours cancer susceptibility v2.17	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480; {Prostate cancer}, OMIM:176807
04 Apr 2022	Adult solid tumours for rare disease v1.30	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480; {Prostate cancer}, OMIM:176807
04 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.8	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Ovarian cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555
04 Apr 2022	Breast cancer pertinent cancer susceptibility v1.6	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Breast cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480
04 Apr 2022	Additional findings health related v0.114	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Breast and ovarian cancer predisposition; Adult only to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480; Adult only
04 Apr 2022	Familial breast cancer v1.17	BRCA2	Arina Puzriakova Phenotypes for gene: BRCA2 were changed from {Breast-ovarian cancer, familial, 2}, 612555; Fanconi anemia, complementation group D1, 605724; Prostate cancer, 176807; {Breast cancer, male, susceptibility to}, 114480; Wilms tumor, 194070; {Medulloblastoma}, 155255; {Glioblastoma 3},; Hereditary Breast and Ovarian Cancer ; Hereditary Breast and Ovarian Cancer Syndrome; Breast and Ovarian Cancer; High Risk Breast Cancer ; Breast cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480
04 Apr 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.540	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Fanconi anemia, complementation group S, 617883; normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure; Fanconi Anemia Type S to Fanconi anemia, complementation group S, OMIM:617883; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure
04 Apr 2022	COVID-19 research v1.119	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Fanconi anemia, complementation group S, 617883; normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure; Fanconi Anemia Type S to Fanconi anemia, complementation group S, OMIM:617883; Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage; Bone marrow failure
04 Apr 2022	Confirmed Fanconi anaemia or Bloom syndrome v1.14	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Fanconi anemia; 617883 Fanconi anemia, complementation group S to Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Haematological malignancies cancer susceptibility v2.24	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Class: BM failure FA, (typ AR); Fanconi anemia; MDS; AML; Squamous cell carcinoma: oral, GI, vulvar to Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Cytopenias and congenital anaemias v1.101	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Fanconi anemia to Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Pigmentary skin disorders v1.47	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from FANCS; FANCONI ANEMIA, COMPLEMENTATION GROUP S to Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Haematological malignancies for rare disease v1.8	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Class: BM failure FA, (typ AR); Fanconi anemia; MDS; AML; Squamous cell carcinoma: oral, GI, vulvar to Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.7	BRCA1	Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic germline BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375). This may warrant an MOI change from 'monoallelic' to 'both mono- and biallelic' to ensure these rarer cases are not missed; however this will be flagged for further review to confirm whether the GMS expert group agrees with the change.
04 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.7	BRCA1	Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
04 Apr 2022	Breast cancer pertinent cancer susceptibility v1.5	BRCA1	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: BRCA1. Tag Q2_22_expert_review tag was added to gene: BRCA1.
04 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.6	BRCA1	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: BRCA1. Tag Q2_22_expert_review tag was added to gene: BRCA1.
04 Apr 2022	Breast cancer pertinent cancer susceptibility v1.5	BRCA1	Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic germline BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375). This may warrant an MOI change from 'monoallelic' to 'both mono- and biallelic' to ensure these rarer cases are not missed; however this will be flagged for further review to confirm whether the GMS expert group agrees with the change.
04 Apr 2022	Breast cancer pertinent cancer susceptibility v1.5	BRCA1	Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
04 Apr 2022	Inherited bleeding disorders v1.166	F12	Arina Puzriakova Tag watchlist was removed from gene: F12. Tag watchlist_moi tag was added to gene: F12.
04 Apr 2022	Familial breast cancer v1.16	BRCA1	Arina Puzriakova Tag watchlist_moi tag was added to gene: BRCA1.
04 Apr 2022	Inherited breast cancer and ovarian cancer v0.17	BRCA1	Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic germline BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375). This may warrant an MOI change from 'monoallelic' to 'both mono- and biallelic' to ensure these rarer cases are not missed; however this will be flagged for further review to confirm whether the GMS expert group agrees with the change.
04 Apr 2022	Inherited breast cancer and ovarian cancer v0.17	BRCA1	Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
04 Apr 2022	Inherited breast cancer and ovarian cancer v0.16	BRCA1	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: BRCA1. Tag Q2_22_expert_review tag was added to gene: BRCA1.
04 Apr 2022	Inherited ovarian cancer (without breast cancer) v2.25	BRCA1	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: BRCA1. Tag Q2_22_expert_review tag was added to gene: BRCA1.
04 Apr 2022	Inherited ovarian cancer (without breast cancer) v2.25	BRCA1	Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375). There are at least two unrelated individuals in literature who were diagnosed with ovarian carcinoma in association with biallelic germline BRCA1 variants. This may warrant an MOI change from 'monoallelic' to 'both mono- and biallelic' to ensure these rarer cases are not missed; however this will be flagged for further review to confirm whether the GMS expert group agrees with the change.
04 Apr 2022	Inherited ovarian cancer (without breast cancer) v2.25	BRCA1	Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
04 Apr 2022	Additional findings health related - CNV analysis adult specific v1.1	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Adult only; Breast and ovarian cancer predisposition to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Adult only
04 Apr 2022	Additional findings health related - adult specific v1.1	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Adult only; Breast and ovarian cancer predisposition to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Adult only
04 Apr 2022	Adult solid tumours for rare disease v1.29	BRCA1	Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from 'monoallelic' to 'both mono- and biallelic' to align with the MOI set on the GMS Adult solid tumours cancer susceptibility (v2.2) panel. Although more rare, biallelic BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375).
04 Apr 2022	Adult solid tumours for rare disease v1.29	BRCA1	Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
04 Apr 2022	Adult solid tumours for rare disease v1.28	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Adult solid tumours cancer susceptibility v2.16	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Fanconi anemia, complementation group S, OMIM:617883
04 Apr 2022	Childhood solid tumours cancer susceptibility v1.16	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
04 Apr 2022	Childhood solid tumours v2.28	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Hereditary Breast and Ovarian Cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
04 Apr 2022	Ovarian cancer pertinent cancer susceptibility v1.6	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Ovarian cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
04 Apr 2022	Breast cancer pertinent cancer susceptibility v1.4	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Breast cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
04 Apr 2022	Additional findings health related v0.113	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Breast and ovarian cancer predisposition; Adult only to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Breast and ovarian cancer predisposition; Adult only
04 Apr 2022	Familial breast cancer v1.16	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from {Breast-ovarian cancer, familial, 1}, 604370; {Pancreatic cancer, susceptibility to, 4}, 614320; Hereditary Breast and Ovarian Cancer ; Hereditary Breast and Ovarian Cancer Syndrome; Breast and Ovarian Cancer; High Risk Breast Cancer ; Breast cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
04 Apr 2022	Familial prostate cancer v1.2	BRCA1	Arina Puzriakova Phenotypes for gene: BRCA1 were changed from to Prostate cancer, MONDO:0008315
04 Apr 2022	Inherited bleeding disorders v1.166	F12	Arina Puzriakova Tag watchlist tag was added to gene: F12.
04 Apr 2022	Inherited bleeding disorders v1.166	F12	Arina Puzriakova Phenotypes for gene: F12 were changed from Coagulaton disorder; Angioedema, hereditary, type 3 (AD); Angioedema, hereditary, type III; Factor 12 deficiency (AR); Factor XII deficiency to Angioedema, hereditary, type III, OMIM:610618; Factor XII deficiency, OMIM:234000
04 Apr 2022	Bleeding and platelet disorders v1.37	F12	Arina Puzriakova Phenotypes for gene: F12 were changed from 234000 Factor XII deficiency; 234000 Factor XII deficiency, hereditary Angioedema type III; 610618 Hereditary Angioedema type III to Angioedema, hereditary, type III, OMIM:610618; Factor XII deficiency, OMIM:234000
04 Apr 2022	Bleeding and platelet disorders v1.36	F12	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: F12. Tag Q2_22_phenotype tag was added to gene: F12. Tag Q2_22_expert_review tag was added to gene: F12.
04 Apr 2022	Bleeding and platelet disorders v1.36	F12	Arina Puzriakova changed review comment from: This gene will be flagged for GMS review regarding the pertinence of monoallelic variants to this panel and whether the MOI should remain as 'both mono- and biallelic' or changed to 'biallelic' only or should be demoted on this panel altogether. Monoallelic variants are associated with hereditary angioedema (MIM# 610618) characterised clinically by recurrent skin swelling, abdominal pain attacks, and episodes of upper airway obstruction but otherwise patients do not display any strong evidence of abnormal bleeding or clotting phenotypes. Biallelic variants cause a separate disorder, factor XII deficiency (MIM# 234000) associated with hypercoagulation which in some cases has been linked to thrombus formation.; to: This gene will be flagged for GMS review regarding the pertinence of monoallelic variants to this panel and whether the MOI should remain as 'both mono- and biallelic' or changed to 'biallelic' only or whether this gene should be demoted on this panel altogether. Monoallelic variants are associated with hereditary angioedema (MIM# 610618) characterised clinically by recurrent skin swelling, abdominal pain attacks, and episodes of upper airway obstruction but otherwise patients do not display any strong evidence of abnormal bleeding or clotting phenotypes. Biallelic variants cause a separate disorder, factor XII deficiency (MIM# 234000) associated with hypercoagulation which in some cases has been linked to thrombus formation.
04 Apr 2022	Bleeding and platelet disorders v1.36	F12	Arina Puzriakova changed review comment from: This gene will be flagged for GMS review regarding the pertinence of monoallelic variants to this panel and whether the MOI should remain as 'both mono- and biallelic' or changed to 'biallelic' only. Monoallelic variants are associated with hereditary angioedema (MIM# 610618) characterised clinically by recurrent skin swelling, abdominal pain attacks, and episodes of upper airway obstruction but otherwise patients do not display any strong evidence of abnormal bleeding or clotting phenotypes. Biallelic variants cause a separate disorder, factor XII deficiency (MIM# 234000) associated with hypercoagulation which in some cases has been linked to thrombus formation.; to: This gene will be flagged for GMS review regarding the pertinence of monoallelic variants to this panel and whether the MOI should remain as 'both mono- and biallelic' or changed to 'biallelic' only or should be demoted on this panel altogether. Monoallelic variants are associated with hereditary angioedema (MIM# 610618) characterised clinically by recurrent skin swelling, abdominal pain attacks, and episodes of upper airway obstruction but otherwise patients do not display any strong evidence of abnormal bleeding or clotting phenotypes. Biallelic variants cause a separate disorder, factor XII deficiency (MIM# 234000) associated with hypercoagulation which in some cases has been linked to thrombus formation.
04 Apr 2022	Vascular skin disorders v1.49	F12	Arina Puzriakova Tag Q2_22_MOI tag was added to gene: F12. Tag Q2_22_expert_review tag was added to gene: F12.
04 Apr 2022	Vascular skin disorders v1.49	F12	Arina Puzriakova Phenotypes for gene: F12 were changed from Angioedema, hereditary, type III, OMIM:610618 to Angioedema, hereditary, type III, OMIM:610618; Factor XII deficiency, OMIM:234000
03 Apr 2022	Intellectual disability v3.1534	ZBTB7A	Konstantinos Varvagiannis gene: ZBTB7A was added gene: ZBTB7A was added to Intellectual disability. Sources: Literature,Other Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZBTB7A were set to 31645653; 34515416 Phenotypes for gene: ZBTB7A were set to Global developmental delay; Intellectual disability; Macrocephaly; Abnormality of the lymphatic system; Sleep apnea; Increased body weight; Autism; Persistence of hemoglobin F; Abnormal leukocyte count; Recurrent infections; Umbilical hernia Penetrance for gene: ZBTB7A were set to unknown Review for gene: ZBTB7A was set to AMBER Added comment: Monoallelic pathogenic ZBTB7A variants cause Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (#619769). ---- Ohishi et al (2020 - PMID: 31645653) described the phenotype of a 6y5m-old male harboring a heterozygous, de novo ZBTB7A missense variant. Features included macrocephaly, mild intellectual disability (tIQ 65) and sleep apnea. Available hemoglobin levels (in the 1st month) supported high Hb and HbF levels. Other features included PDA and an umbilical hernia. Initial investigations incl. karyotype and CMA were normal. The ZBTB7A variant (NM_015898.3:c.1152C>G / p.Cys384Tyr) was identified following trio WES with a list of additional findings (in suppl.) not explaining the phenotype. This SNV, confirmed by Sanger sequencing, was absent from public db with several in silico predictions in favor of a deleterious effect. ZBTB7A on 19p encodes zinc finger- and BTB domain-containing protein 7 (or Pokemon). The authors performed a review of 19p13.3 microdeletion cases supporting a minimum region of overlap spanning PIAS4, ZBTB7A and MAP2K2 and common features of DD and ID, macrocephaly with prominent forehead, sleep apnea. The authors argue that loss of ZBTB7A explains part of - but probably not all - features of 19p13.3 microdeletions. ZBTB7A is known to repress expression of HBG1 and HBG2 (γ-globin), with the few available HbF patient measurements in line with this role. Based on the structure of the protein, Cys384 (along with 3 other residues) forms a coordinate bond with the Zn+2 ion, this bond predicted to be disrupted by Tyr. Further they favor a dominant negative effect given that ZBTB7A protein is known to form dimer via interaction at the BTB domain [hetero (variant+wt) and homodimers (variant+variant) having compromised function]. To support this notion, 3 previously reported somatic variants within the zinc-finger domain have been shown to exert a dominant-negative effect (PMID cited: 26455326). ---- In a collaborative study, von der Lippe et al (2022 - PMID: 34515416) identified 12 additional individuals (from 10 families) harboring monoallelic ZBTB7A missense/pLoF variants most commonly as de novo events. The authors describe a consistent phenotype with motor (9/11) and speech delay (9/12), cognitive impairment/ID (12/12 - commonly mild, ranged from specific learning difficulties to severe ID), macrocephaly (>90%le in 11/12, >97% in 7/12), lymphoid hypertrophy of pharyngeal tissue/adenoid overgrowth (12/12), sleep apnea (9/12). Autistic features were observed in 7/12. Other phenotypes included frequent upper airway infections (10/11), weight above 97th percentile (7/11). HbF levels were elevated in 4/5 individuals with available measurements (range: 2.2% to 11.2% - ref. for subjects above 6m of age : <2% ). Other hematological issues were observed in few individuals (abn. monocyte/neutrophil counts in 3-4). Cardiovascular issues were reported in 4 (2 fam). 3 subjects had umbilical hernia. There was no common dysmorphic feature. Various initial investigations were normal or did not appear to explain the NDD phenotype and incl. standard karyotype, CMA, targeted testing for genes/disorders previously considered (PTEN, FMR1, NSD1, BWS and PWS methylation studies, CFTR, etc). One male had a maternally inherited chrX dup not thought to explain his complex phenotype, while another had a concurrent diagnosis of thalassemia. Individuals were investigated with singleton (or trio) WES. Of note some individuals were DDD study participants. 8 had de novo ZBTB7A variants, incl. one who harbored 2 de novo missense SNVs several residues apart. 2 sibs had inherited a fs variant from their affected parent. For the latter as well as for another subject parental samples were unavailable. There were no other variants of interest upon exome analysis. 5 different missense, 2 nonsense and 3 fs variants were identified with pLoF all predicted to lead to NMD. All variants were absent from gnomAD (pLI of 0.96, LOEUF 0.33 and missense Z-score of 4.04) which lists one individual with htz LoF, likely not an artifact. Given this individual (and the familial case) the authors discuss on the mild phenotype and/or eventual reduced penetrance or underdiagnosis of the disorder. There was no difference in severity between those with missense/truncating variants. ZBTB7A transcription factor (or pokemon or lymphoma/leukemia-related factor) is widely expressed. It is involved in several activities being among others required to block Notch signaling which in turn drives T-cell at the expense of B-cell development. Notch pathway activation has been demonstrated in Zbtba7 ko mouse models. Finally, the authors discuss the role of notch signaling in thymus and the nervous system, as well as that ZBTB7A up/down-regulation known to repress/increase respectively HbF expression (several refs in text). ---- MGI (1335091) for Zbtb7a : "Mice homozygous for a knock-out allele die around E16.5 due to anemia and exhibit a cell autonomous defect in early B cell development". (Phenotypes from nervous system not commented on). ---- Apart from OMIM (#619769), ZBTB7A is included in the DD panel of G2P (ZBTB7A-associated developmental disorder / monoallelic_autosomal / absent gene product / confidence limited) as well as among the primary ID genes in SysID. In PanelApp Australia the gene is incl. with green rating in the ID and Macrocephaly gene panels. ---- Consider inclusion with amber or green rating (several individuals/families/variants, highly consistent phenotype, overlap with 19p microdeletions \|\| variant effect not studied, animal models supporting contribution of the gene to the phenotype though no data on associated NDD ones). Please also consider inclusion in other relevant panels (macrocephaly, lymphatic disorders, ASD, etc). Sources: Literature, Other
02 Apr 2022	Early onset or syndromic epilepsy v2.504	ATP2B1	Konstantinos Varvagiannis gene: ATP2B1 was added gene: ATP2B1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP2B1 were set to 35358416; 33057194 Phenotypes for gene: ATP2B1 were set to Global developmental delay; Intellectual disability; Autism; Behavioral abnormality; Seizures; Abnormality of head or neck Penetrance for gene: ATP2B1 were set to unknown Review for gene: ATP2B1 was set to AMBER Added comment: At least 12 individuals with NDD due to monoallelic missense/pLoF ATP2B1 variants have been reported to date. Seizures were observed in 5 of them. Currently there is no associated phenotype in OMIM, G2P, SysID, PanelApp Australia. Based also on the evidence discussed below, please consider inclusion with amber rating. --- Rahimi et al (2022 - PMID: 35358416) describe 12 unrelated individuals with monoallelic ATP2B1 variants. Phenotype consisted of DD (12/12), ID [9/12 - mild or less commonly moderate, with 3 additional subjects "unclassified" likely due to their age (#6: 3y nonverbal/nonambulatory, could sit and roll / #8: 3y, sitting at 1y, 1st words:26m / #12: at 5y nonambulatory/nonverbal)]. Behavioral issues were observed in 8/11 (ASD in 5/11). Seizures were reported in 5/12 (one further had abnormal EEG). Minor features - albeit not consistent/without recognizable gestalt - were reported in 6. Anomalies of digits and marfanoid habitus were reported in 4 and 2. All subjects were investigated by singleton/trio exome sequencing. Previous investigations incl. karyotype, CMA, analysis of individual genes (e.g. FMR1, ZEB2) or metabolic workup were normal for several individuals with one having a concurrent diagnosis of mosaic (20%) XXY and another harboring an additional hmz variant for a liver disorder. 9 different missense and 3 nonsense ATP2B1 variants were identified, shown to have occurred de novo in all cases where parental samples were available (9/12). ATPase plasma membrane Ca+2 transporting 1, the protein encoded by ATP2B1, is an ATP-driven calmodulin-dependent Ca+2 pump which removes intracellular calcium from the cytosol. As the authors comment calcium pumps are thought to have a crucial role on neuronal function. All variants identified were absent from gnomAD with the exception of c.2365C>T / p.Arg789Cys (de novo) which is present once in the database. ATP2B1 has a pLI of 1 and a missense Z-score of 5.29. The variants affected several ATP2B1 isoforms. Variants were reported using NM_001001323.2, corresponding to ATP2B1a isoform which is mainly detected in brain (as also in GTEx). In silico predictions were in favor of a deleterious effect and structural modeling supported the role of the affected residues. The nonsense variants occurred in positions predicted to lead to NMD (not studied). Transfection of an ATP2B1-yellow fluorescent protein (YFP) expression plasmid for wt or variants in HEK293 cells, revealed membranous fluorescence for wt, significantly altered localization for 3 variants (Asp239Gly, Thr264Ile, Arg991Gln), shift to cytoplasmic localization for 4 others (Thr425Lys, Arg763Pro, Glu824Lys, Gln857Arg) with statistically non-significant effect for 2 others (His459Arg and Arg789Cys). Fluorometric [Ca+2]i analysis in HEK293 cells expressing wt or variant ATP2B1 revealed that all missense variants affected Ca+2 transport. This was not the case for wt ATP2B1 or for another missense variant used as control (drawn from gnomAD). Of note, a further (13th) affected individual with another missense variant (c.1793T>C / p.Ile598Thr) was excluded from the phenotypic analysis. The membrane localization and Ca+2 transport did not appear to be affected by this variant which was classified as VUS although it a different impact from those studied. Overall loss-of-function is thought to be the underlying mechanism based on the above (and supported by few reported cases with gross deletions spanning also ATP2B1). A dominant negative effect for missense variants (affecting heteromeric complex formation with neuroplastin or basigin) could not be completely excluded, but not supported either by the localization of the identified variants. In the supplement the authors include 3 DDD study participants previously reported to harbor de novo pLoF/missense variants though with few available clinical information (PMID: 33057194 - DDD13k.05076 : c.2883del / DDD13k.04028 : c2512A>C - p.Ile838Val / DDD13k.08944 : c.2129A>C - p.Asp710Ala). The authors discuss on the role of ATP2B1 on Ca+2 homeostasis in the CNS and neurodevelopment overall (also based on isoform expression in rat brain). Sources: Literature
02 Apr 2022	Intellectual disability v3.1534	ATP2B1	Konstantinos Varvagiannis gene: ATP2B1 was added gene: ATP2B1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP2B1 were set to 35358416; 35358416 Phenotypes for gene: ATP2B1 were set to Global developmental delay; Intellectual disability; Autism; Behavioral abnormality; Seizures; Abnormality of head or neck Penetrance for gene: ATP2B1 were set to unknown Review for gene: ATP2B1 was set to GREEN Added comment: Monoallelic missense/pLoF ATP2B1 variants have been reported in 12 unrelated individuals with DD/ID making this gene relevant to the current panel. Currently there is no associated phenotype in OMIM, G2P, SysID, PanelApp Australia. Based also on the evidence discussed below, please consider inclusion with green (rather than amber) rating. --- Rahimi et al (2022 - PMID: 35358416) describe 12 unrelated individuals with monoallelic ATP2B1 variants. Phenotype consisted of DD (12/12), ID [9/12 - mild or less commonly moderate, with 3 additional subjects "unclassified" likely due to their age (#6: 3y nonverbal/nonambulatory, could sit and roll / #8: 3y, sitting at 1y, 1st words:26m / #12: at 5y nonambulatory/nonverbal)]. Behavioral issues were observed in 8/11 (ASD in 5/11). Seizures were reported in 5/12 (one further had abnormal EEG). Minor features - albeit not consistent/without recognizable gestalt - were reported in 6. Anomalies of digits and marfanoid habitus were reported in 4 and 2. All subjects were investigated by singleton/trio exome sequencing. Previous investigations incl. karyotype, CMA, analysis of individual genes (e.g. FMR1, ZEB2) or metabolic workup were normal for several individuals with one having a concurrent diagnosis of mosaic (20%) XXY and another harboring an additional hmz variant for a liver disorder. 9 different missense and 3 nonsense ATP2B1 variants were identified, shown to have occurred de novo in all cases where parental samples were available (9/12). ATPase plasma membrane Ca+2 transporting 1, the protein encoded by ATP2B1, is an ATP-driven calmodulin-dependent Ca+2 pump which removes intracellular calcium from the cytosol. As the authors comment calcium pumps are thought to have a crucial role on neuronal function. All variants identified were absent from gnomAD with the exception of c.2365C>T / p.Arg789Cys (de novo) which is present once in the database. ATP2B1 has a pLI of 1 and a missense Z-score of 5.29. The variants affected several ATP2B1 isoforms. Variants were reported using NM_001001323.2, corresponding to ATP2B1a isoform which is mainly detected in brain (as also in GTEx). In silico predictions were in favor of a deleterious effect and structural modeling supported the role of the affected residues. The nonsense variants occurred in positions predicted to lead to NMD (not studied). Transfection of an ATP2B1-yellow fluorescent protein (YFP) expression plasmid for wt or variants in HEK293 cells, revealed membranous fluorescence for wt, significantly altered localization for 3 variants (Asp239Gly, Thr264Ile, Arg991Gln), shift to cytoplasmic localization for 4 others (Thr425Lys, Arg763Pro, Glu824Lys, Gln857Arg) with statistically non-significant effect for 2 others (His459Arg and Arg789Cys). Fluorometric [Ca+2]i analysis in HEK293 cells expressing wt or variant ATP2B1 revealed that all missense variants affected Ca+2 transport. This was not the case for wt ATP2B1 or for another missense variant used as control (drawn from gnomAD). Of note, a further (13th) affected individual with another missense variant (c.1793T>C / p.Ile598Thr) was excluded from the phenotypic analysis. The membrane localization and Ca+2 transport did not appear to be affected by this variant which was classified as VUS although it a different impact from those studied. Overall loss-of-function is thought to be the underlying mechanism based on the above (and supported by few reported cases with gross deletions spanning also ATP2B1). A dominant negative effect for missense variants (affecting heteromeric complex formation with neuroplastin or basigin) could not be completely excluded, but not supported either by the localization of the identified variants. In the supplement the authors include 3 DDD study participants previously reported to harbor de novo pLoF/missense variants though with few available clinical information (PMID: 33057194 - DDD13k.05076 : c.2883del / DDD13k.04028 : c2512A>C - p.Ile838Val / DDD13k.08944 : c.2129A>C - p.Asp710Ala). The authors discuss on the role of ATP2B1 on Ca+2 homeostasis in the CNS and neurodevelopment overall (also based on isoform expression in rat brain). Sources: Literature
01 Apr 2022	Retinal disorders v2.251	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27302843; 32866347; 31884617; 29676688; 26387595; 29220678; 21937992
01 Apr 2022	Retinal disorders v2.250	PEX6	Sarah Leigh commented on gene: PEX6: Retinal involvement is mentioned in Peroxisome biogenesis disorder 4B (OMIM:614863)(PMID:21937992; 22871920).
01 Apr 2022	Retinal disorders v2.250	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27302843; 32866347; 31884617; 29676688; 26387595; 29220678
01 Apr 2022	Retinal disorders v2.249	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to None
01 Apr 2022	Retinal disorders v2.248	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Retinal disorders v2.248	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Heimler syndrome 2, OMIM:616617, MONDO:0014709 to Heimler syndrome 2, OMIM:616617; MONDO:0014709; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Retinal disorders v2.247	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27302843; 32866347; 31884617; 29676688; 26387595
01 Apr 2022	Retinal disorders v2.246	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Retinal disorders v2.246	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Retinal disorders v2.245	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Arthrogryposis v3.158	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Arthrogryposis v3.157	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: Arthrogryposis maybe over looked in patients with Peroxisome biogenesis disorder 4A (Zellweger) (OMIM:614862) and Peroxisome biogenesis disorder 4B (OMIM:6148630), as these conditions are characterized by a severe phenotype and premature death in some cases. If this is the case, for Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) have identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Arthrogryposis v3.157	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Arthrogryposis v3.157	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger) 614862 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Arthrogryposis v3.156	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 20301621
01 Apr 2022	Arthrogryposis v3.155	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Arthrogryposis v3.155	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.233	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to None
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.232	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.231	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 25655951
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.230	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.230	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.229	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.229	PEX6	Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Undiagnosed metabolic disorders v1.521	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Undiagnosed metabolic disorders v1.520	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4A (Zellweger) 614862; Peroxisome biogenesis disorder 4B 614863 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Undiagnosed metabolic disorders v1.519	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27604308
01 Apr 2022	Undiagnosed metabolic disorders v1.518	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Undiagnosed metabolic disorders v1.518	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Undiagnosed metabolic disorders v1.517	PEX6	Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Peroxisomal disorders v1.19	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Peroxisomal disorders v1.18	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Peroxisomal disorders v1.18	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Peroxisomal disorders v1.17	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Peroxisomal disorders v1.17	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Malformations of cortical development v2.141	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to None
01 Apr 2022	Malformations of cortical development v2.140	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Malformations of cortical development v2.140	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Malformations of cortical development v2.140	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Malformations of cortical development v2.140	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Malformations of cortical development v2.139	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4A (Zellweger), 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Malformations of cortical development v2.138	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27604308
01 Apr 2022	Intellectual disability v3.1534	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Intellectual disability v3.1533	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Intellectual disability v3.1533	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Intellectual disability v3.1532	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), 614862Peroxisome biogenesis disorder 4B, 614863; ZELLWEGER SYNDROME (ZWS) to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Intellectual disability v3.1531	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	Intellectual disability v3.1530	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Intellectual disability v3.1530	PEX6	Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Likely inborn error of metabolism v2.239	PEX6	Sarah Leigh Mode of pathogenicity for gene PEX6 was changed from to Other Penetrance for gene PEX6 was set from to None
01 Apr 2022	Likely inborn error of metabolism v2.238	PEX6	Sarah Leigh commented on gene: PEX6: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).
01 Apr 2022	Likely inborn error of metabolism v2.238	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Likely inborn error of metabolism v2.238	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Likely inborn error of metabolism v2.237	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.154	PEX6	Sarah Leigh Mode of pathogenicity for gene PEX6 was changed from to Other Penetrance for gene PEX6 was set from to None
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.153	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.153	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.153	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.153	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.152	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A, 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Hereditary ataxia with onset in adulthood v2.151	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	Fetal hydrops v1.55	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Fetal hydrops v1.54	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Fetal hydrops v1.54	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 20033294; 23137060
01 Apr 2022	Fetal hydrops v1.53	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Fetal hydrops v1.53	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Fetal hydrops v1.52	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Fetal hydrops v1.52	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Zellweger, peroxisome biogenesis disorder 4A, 4B; Peroxisome biogenesis disorder 4A (Zellweger), 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Fetal hydrops v1.51	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	DDG2P v2.69	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to None
01 Apr 2022	Fetal anomalies v1.848	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to None
01 Apr 2022	Fetal anomalies v1.847	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Fetal anomalies v1.847	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4; ZELLWEGER SYNDROME to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Fetal anomalies v1.846	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	Fetal anomalies v1.845	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Fetal anomalies v1.845	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Fetal anomalies v1.844	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	DDG2P v2.68	PEX6	Sarah Leigh changed review comment from: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; to: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).
01 Apr 2022	DDG2P v2.68	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	DDG2P v2.67	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed phenotypes to: 29220678; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	DDG2P v2.67	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal in order to detect the dominant Peroxisome biogenesis disorder 4B. Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	DDG2P v2.67	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	DDG2P v2.66	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	DDG2P v2.66	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from ZELLWEGER SYNDROME 214100; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4 601498 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Amelogenesis imperfecta v2.19	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Amelogenesis imperfecta v2.18	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed publications to: 29220678
01 Apr 2022	Amelogenesis imperfecta v2.18	PEX6	Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
01 Apr 2022	Amelogenesis imperfecta v2.18	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal in order to detect the dominant Peroxisome biogenesis disorder 4B. Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
01 Apr 2022	Amelogenesis imperfecta v2.18	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Amelogenesis imperfecta v2.17	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 27302843; 26387595; 16530715
01 Apr 2022	Amelogenesis imperfecta v2.16	PEX6	Sarah Leigh edited their review of gene: PEX6: Added comment: The review by Claire Smith (University of Leeds)(below), states that amelogenesis imperfecta maybe over looked in patients with Peroxisome biogenesis disorder 4A (Zellweger) (OMIM:614862) and Peroxisome biogenesis disorder 4B (OMIM:6148630), as these conditions are characterized by a severe phenotype and premature death in some cases. With this in mind the Peroxisome biogenesis disorder 4B (OMIM:614863) could be relevant to this panel and such the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal in order to detect variants resulting in allelic expression imbalance and dominant-negative effect (PMID: 29220678).; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Amelogenesis imperfecta v2.16	PEX6	Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Heimler syndrome 2, OMIM:616617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Bilateral congenital or childhood onset cataracts v2.104	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger); Confirmed DD gene for ZELLWEGER SYNDROME; Peroxisome biogenesis disorder to Heimler syndrome 2, OMIM:616617
01 Apr 2022	Bilateral congenital or childhood onset cataracts v2.103	PEX6	Sarah Leigh Publications for gene: PEX6 were set to
01 Apr 2022	Bilateral congenital or childhood onset cataracts v2.102	PEX6	Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: None; Publications: 26387595; Phenotypes: Heimler syndrome 2 OMIM:616617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Inherited white matter disorders v1.157	PEX6	Sarah Leigh Penetrance for gene PEX6 was set from to Complete
01 Apr 2022	Inherited white matter disorders v1.156	PEX6	Sarah Leigh Added comment: Comment on mode of inheritance: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230.
01 Apr 2022	Inherited white matter disorders v1.156	PEX6	Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
01 Apr 2022	Inherited white matter disorders v1.155	PEX6	Sarah Leigh Mode of pathogenicity for gene: PEX6 was changed from None to Other
01 Apr 2022	Inherited white matter disorders v1.154	PEX6	Sarah Leigh Added comment: Comment on mode of pathogenicity: Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678).
01 Apr 2022	Inherited white matter disorders v1.154	PEX6	Sarah Leigh Mode of pathogenicity for gene: PEX6 was changed from to None
01 Apr 2022	Inherited white matter disorders v1.153	PEX6	Sarah Leigh Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger) 614862; Peroxisome biogenesis disorder 4B 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
01 Apr 2022	Inherited white matter disorders v1.152	PEX6	Sarah Leigh Publications for gene: PEX6 were set to 25655951
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.229	PNPT1	Arina Puzriakova Classified gene: PNPT1 as Amber List (moderate evidence)
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.229	PNPT1	Arina Puzriakova Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
01 Apr 2022	White matter disorders and cerebral calcification - narrow panel v1.228	PNPT1	Arina Puzriakova gene: PNPT1 was added gene: PNPT1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature Q1_22_rating tags were added to gene: PNPT1. Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPT1 were set to 28594066; 30046113; 33199448 Phenotypes for gene: PNPT1 were set to Combined oxidative phosphorylation deficiency 13, OMIM:614932 Review for gene: PNPT1 was set to GREEN Added comment: White matter abnormalities can be observed in some patients with PNPT1-related mitochondrial disease caused by biallelic variants. Overall at 6 least unrelated cases reported in literature with diminished white matter and/or delayed myelination which is sufficient to justify a Green rating on this panel. Sources: Literature
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.225	PNPT1	Arina Puzriakova edited their review of gene: PNPT1: Changed rating: GREEN
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.225	PNPT1	Arina Puzriakova Publications for gene: PNPT1 were set to 23084291; 33199448
01 Apr 2022	Primary ciliary disorders v1.40	XPNPEP3	Sarah Leigh commented on gene: XPNPEP3: Helen Brittain (GEL Clinical Fellow) agrees with the review from Ian Berry (below) that this gene is not relevant for Primary ciliary disorders. XPNPEP3 is recommended to be green on Renal ciliopathies (https://panelapp.genomicsengland.co.uk/panels/725/gene/XPNPEP3/#!review).
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.224	PNPT1	Arina Puzriakova Classified gene: PNPT1 as Amber List (moderate evidence)
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.224	PNPT1	Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there are sufficient unrelated cases to rate this gene as Green at the next GMS review.
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.224	PNPT1	Arina Puzriakova Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.223	PNPT1	Arina Puzriakova Publications for gene: PNPT1 were set to
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.222	PNPT1	Arina Puzriakova Tag Q1_22_rating tag was added to gene: PNPT1.
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.222	PNPT1	Arina Puzriakova reviewed gene: PNPT1: Rating: ; Mode of pathogenicity: None; Publications: 33199448; Phenotypes: Combined oxidative phosphorylation deficiency 13, OMIM:614932; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
01 Apr 2022	Childhood onset dystonia, chorea or related movement disorder v1.222	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13, 614932 to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Dystonia
01 Apr 2022	Adult onset dystonia, chorea or related movement disorder v1.168	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13, 614932; Dystonia to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Dystonia
01 Apr 2022	Monogenic hearing loss v2.238	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934 to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934
01 Apr 2022	Mitochondrial disorders v2.96	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934; respiratory chain disorder; hearing loss to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
01 Apr 2022	Likely inborn error of metabolism v2.237	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; respiratory chain disorder; hearing loss; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
01 Apr 2022	Possible mitochondrial disorder - nuclear genes v1.70	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Deafness, autosomal recessive 70, 614934; Combined oxidative phosphorylation deficiency 13, 614932 to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
01 Apr 2022	Undiagnosed metabolic disorders v1.517	PNPT1	Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934; respiratory chain disorder; hearing loss to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
31 Mar 2022	Intellectual disability v3.1530	MAN2C1	Konstantinos Varvagiannis gene: MAN2C1 was added gene: MAN2C1 was added to Intellectual disability. Sources: Literature,Other Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2C1 were set to 35045343 Phenotypes for gene: MAN2C1 were set to Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Abnormality of the corpus callosum; Ventriculomegaly; Polymicrogyria; Abnormality of the face; Macrocephaly Penetrance for gene: MAN2C1 were set to unknown Review for gene: MAN2C1 was set to GREEN Added comment: Biallelic pathogenic MAN2C1 variants cause Congenital disorder of deglycosylation 2 (# 619775). Mild to moderate impairment of intellectual development is a feature in most patients as in the OMIM's clinical synopsis for this disorder. ---- Specifically, Maia et al (2022 - PMID: 35045343) report the clinical features based of 6 relevant individuals (4/6 aged 4-18years and 2/6 fetuses) from 4 families. These individuals had non-specific dysmorphic features (micro/retrognathia being the most common in 5/6), different congenital anomalies, variable degrees of ID (3/4), as well as brain MRI abnormalities (PMG in 3/6 from 3 fam, ventriculomegaly in 3/6 from 2 fam, callosal anomalies in 4/6 from 3 fam, cerebellar hypoplasia 2/6 - 2 fam, vermis hypoplasia 4/6 - 3 fam etc). Macrocephaly was reported for 2/6 individuals (2 fam). While ID was observed in 3/4 individuals of relevant age (mild in 1/4, moderate in 1/4, unk in 1/4), delayed motor and language development was reported for all (4/4). All individuals harbored biallelic MAN2C1 variants following exome sequencing (previous investigations not reported), and Sanger sequencing was used for validation and segregation (parents/sibs). There were no putative pathogenic variants in known disease genes. MAN2C1 encodes mannosidase, alpha, class 2c, member 1, an enzyme playing a role in deglycosylation of free oligosaccharides (fOSs). The latter are generated and released in the cytoplasm or the ER lumen during N-glycosylation of proteins. fOSs are generated from two different pathways (ERAD and LLO) with a defect in an enzyme of the NGLY1 already described to cause a NDD due to defect of deglycosylation. In a later step oligossaccharides are trimmed by the action of ENGase to form fOS containing one GlcNAc (N-Acetylglucosamine) residue (fOSGn1) at the reducing end. Processing of these fOSs by the cytosolic α-mannosidase (MAN2C1) converts Man7-9Gn1 to Man5Gn1 subsequently transported to lysosomes for degradation. Variants incl. 3 missense SNVs incl. c.2612G>C/p.Cys871Ser, c.2303G>A/p.Arg768Gln, c.607G>A/p.Gly203Arg, one splice variant (c.601-2A>G/p.Gly201Profs10) and one indel (c.2733_2734del/p.His911Glnfs67). [RefSeq NM_006715.3] Most were present in gnomAD with low AF ranging from 0.013% to 0.11% while c.2303G>A/p.Arg768 has an AF of 0.33% with 5 homozygotes() in the database. Conservation and in silico predictions supported their effect. For the variant affecting the splicing acceptor site (c.601-2A>G) studies in patient fibroblasts confirmed skipping of ex6. Fibroblasts from 2 sibs cmp htz for Arg768Gln and c.601-2A>G (Gly201Profs10) were studied for protein levels, demonstrating 90% reduction in the amount of MAN2C1. There was no truncated protein observed upon immunoblot. Protein abundance was not affected in fibroblasts from the individual who was homozygous for Gly203Arg. Mannosidase activities were studied upon overexpression in a HEK293 model, with Gly203Arg presenting similar activity to WT and Arg768Gln exhibiting only a tiny residual activity. Cys871Ser showed increased activity compared to WT. Using fibroblasts from controls and the same individuals as above, the authors showed that pathogenic MAN2C1 variants caused defects in fOS processing (delayed processing of high oligomannose species, reduced production of M5Gn1 with M8 and M9Gn1/2 species remaining at high levels) supporting a total/partial loss of mannosidase activity for Arg768Gln and Gly203Arg. In MAN2C1-KO HAP1 cell lines, M7-M9Gn1 species accumulated while M5Gn1 - the product of MAN2C1 - were absent. Complementation of KO HAP1 cells with Gly203Arg, Arg768Gln and Cys871Ser suggested impaired fOS processing for Gly203Arg and Arg768Gln (with significant amounts of M7-M9Gn1 species). Cells complemented with Cys871Ser did not exhibit fOS processing defects. The authors speculate that Cys871Ser could affect a non-mannosidase function of the enzyme relevant to brain development or that it might lead to abnormal inter-subunit interactions or tetramer formation. Finally, Maia et al summarize findings in previously described Man2c1-KO mice (cited PMID: 24550399). These appeared normal, did not exhibit differences in growth or lifespan and did not present behavioral alterations. Man2c1-KO mice had CNS involvement with histological analyses in favor of neuronal and glial degeneration with multiple vacuoles in deep neocortical layers and telencephalic white matter tracts. Vacuolization was not observed upon brain histology for the 2 fetuses studied which Maia et al speculate may occur at a later stage. In KO mice there was considerable accumulation of Man8–9GlcNAc oligosaccharides. ---- G2P includes MAN2C1 in it's DD panel (confidence: strong, MAN2C1-associated neurodevelopmental disorder with cerebral malformations). In PanelApp Australia, this gene is rated green in the ID, polymicrogyria, cerebellar hypoplasia and fetal anomalies gene panels. Consider inclusion in the current panel with green (3 individuals/families/variants, role of the gene, NDD phenotype also reported for NGLY1-related disorder of deglycosylation, variant studies) or amber rating (ID not a universal feature, still DD observed in all affected individuals). Please consider adding this gene in other relevant panels (as in PanelApp Australia, also for corpus callosum abnormalities, metabolic disorders, etc). Sources: Literature, Other
31 Mar 2022	Intellectual disability v3.1530	TLK2	Arina Puzriakova Publications for gene: TLK2 were set to 27479843; https://doi.org/10.1016/j.ajhg.2018.04.014
31 Mar 2022	Rare syndromic craniosynostosis or isolated multisuture synostosis v2.68	SIX1	Arina Puzriakova Publications for gene: SIX1 were set to
31 Mar 2022	Cystic kidney disease v2.41	ZNF423	Arina Puzriakova commented on gene: ZNF423: There are now two unrelated families with homozygous variants and two cases with heterozygous variants in this gene associated with nephronophthisis or Joubert syndrome. Zfp423-mutant mice harbouring some variants (but not all - including one patient variant) displayed neuroanatomical abnormalities that were consistent with the human phenotype. Overall the evidence is borderline and therefore this gene will be flagged for GMS expert review to determine whether it should be upgraded to green at this stage.
31 Mar 2022	Cystic kidney disease v2.41	ZNF423	Arina Puzriakova reviewed gene: ZNF423: Rating: ; Mode of pathogenicity: None; Publications: 22863007, 32925911, 33323469; Phenotypes: Joubert syndrome 19, OMIM:614844, Nephronophthisis 14, OMIM:614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
31 Mar 2022	Cystic kidney disease v2.41	ZNF423	Arina Puzriakova Tag Q1_22_expert_review tag was added to gene: ZNF423.
31 Mar 2022	Cystic kidney disease v2.41	ZNF423	Arina Puzriakova Classified gene: ZNF423 as Amber List (moderate evidence)
31 Mar 2022	Cystic kidney disease v2.41	ZNF423	Arina Puzriakova Gene: znf423 has been classified as Amber List (Moderate Evidence).
31 Mar 2022	Cystic kidney disease v2.40	ZNF423	Arina Puzriakova Publications for gene: ZNF423 were set to
31 Mar 2022	Neurological ciliopathies v1.31	ZNF423	Arina Puzriakova Publications for gene: ZNF423 were set to
31 Mar 2022	Neurological ciliopathies v1.30	ZNF423	Arina Puzriakova Tag Q1_22_expert_review tag was added to gene: ZNF423.
31 Mar 2022	Neurological ciliopathies v1.30	ZNF423	Arina Puzriakova commented on gene: ZNF423: There are now two unrelated families with homozygous variants and two cases with heterozygous variants in this gene associated with nephronophthisis or Joubert syndrome. Zfp423-mutant mice harbouring some variants (but not all - including one patient variant) displayed neuroanatomical abnormalities that were consistent with the human phenotype. Overall the evidence is borderline and therefore this gene will be flagged for GMS expert review to determine whether it should be upgraded to green at this stage.
31 Mar 2022	Neurological ciliopathies v1.30	ZNF423	Arina Puzriakova reviewed gene: ZNF423: Rating: ; Mode of pathogenicity: None; Publications: 22863007, 32925911, 33323469; Phenotypes: Joubert syndrome 19, OMIM:614844, Nephronophthisis 14, OMIM:614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
31 Mar 2022	Ophthalmological ciliopathies v1.30	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Nephronophthisis 14; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14, 614844 to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Rare multisystem ciliopathy disorders v1.160	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Joubert syndrome 19, 614844; Nephronophthisis 14, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14 to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Neurological ciliopathies v1.30	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Nephronophthisis 14; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14, 614844 to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.221	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Joubert syndrome 19; Nephronophthisis 14; Nephronophthisis 14, 614844; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Unexplained young onset end-stage renal disease v1.34	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Ciliopathy genes associated with cystic kidney disease to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Cystic kidney disease v2.39	ZNF423	Arina Puzriakova Mode of inheritance for gene: ZNF423 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
31 Mar 2022	Tubulointerstitial kidney disease v1.19	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Joubert syndrome 19 MIM 614844; Nephronopthisis 14 to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Cystic kidney disease v2.38	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Ciliopathy genes associated with cystic kidney disease to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Unexplained kidney failure in young people v1.106	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Ciliopathy genes associated with cystic kidney disease to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Renal ciliopathies v1.63	ZNF423	Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Nephronophthisis 14; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect; Joubert syndrome 19; Nephronophthisis 14, 614844 to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
31 Mar 2022	Renal ciliopathies v1.62	ZNF423	Arina Puzriakova Publications for gene: ZNF423 were set to 22863007
31 Mar 2022	Renal ciliopathies v1.61	ZNF423	Arina Puzriakova commented on gene: ZNF423: There are now two unrelated families with homozygous variants and two cases with heterozygous variants in this gene associated with nephronophthisis or Joubert syndrome. Zfp423-mutant mice harbouring some variants (but not all - including one patient variant) displayed neuroanatomical abnormalities that were consistent with the human phenotype. Overall the evidence is borderline and therefore this gene will be flagged for GMS expert review to determine whether it should be upgraded to green at this stage.
31 Mar 2022	Renal ciliopathies v1.61	ZNF423	Arina Puzriakova Tag Q1_22_expert_review tag was added to gene: ZNF423.
30 Mar 2022	Early onset or syndromic epilepsy v2.504	SLC38A3	Konstantinos Varvagiannis gene: SLC38A3 was added gene: SLC38A3 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC38A3 were set to 34605855 Phenotypes for gene: SLC38A3 were set to Infantile axial hypotonia; Global developmental delay; Intellectual disability; Seizures; Spasticity; Microcephaly; Cerebral atrophy; Cerebellar atrophy; Abnormality of the corpus callosum; Dysphagia; Constipation; Increased serum lactate; Hyperammonemia Penetrance for gene: SLC38A3 were set to Complete Review for gene: SLC38A3 was set to GREEN Added comment: Marafi et al (2021 - PMID: 34605855) describe the phenotype of 10 individuals, belonging to 7 families (6/7 consanguineous), harboring biallelic deleterious SLC38A3 variants. One subject (from fam3) was previously reported in the context of a larger cohort of consanguineous families investigated with exome sequencing (2017, PMID: 31130284). The phenotype overall corresponded to a DEE and features included axial hypotonia (10/10), severe global DD or ID (10/10), seizures (8/10, onset : 1w-15m, NOT observed in 2/10 aged 1y3m and 4y \| s. types: tonic-clonic in 3/8, tonic 2/8, focal 2/8 with secondary generalization, myoclonic 1/8, gelastic 1/8 \| EEG burst-suppression, hypsarrhythmia in few). Microcephaly was observed in (8/10) and was more commonly postnatal and/or progressive. Variable abnormalities were observed upon brain imaging incl. cerebral (5/10) or cerebellar atrophy (2/10) and abnormal CC (6/10), abnormal myelination for age (6/10). Other phenotypes included visual impairment (9/10), peripheral hypertonia (8/9) constipation (8/9) and dysphagia (7/9), FTT (4/8), movement disorder (3/10). Metabolic studies indicated (transient) elevation of lactate (7/8 - also pyruvate in 2) and elevated plasma ammonia (4/7). Individuals from the 1st family were investigated with ES, and the SLC38A3 splice site variant (NM_006841.6:c.855+1G>T) was the most likely candidate, additional SNVs not contributing to the NDD phenotype. Other affected subjects were ascertained through GeneMatcher/collaborations. In total, 3 different missense and 4 pLoF (1 fs, 2 nonsense, 1 splicing) variants were identified with individuals from 2 families being hmz or cmd htz for missense variants. Variants were absent/ultrarare with no homozygotes in public/in-house databases with several in silico predictions in favor of a deleterious effect. Regions of AOH (around SLC38A3/total) are provided for some individuals/families. Sanger sequencing was used for confirmation and segregation studies (apart from carrier parents in 7/7 fam, 11 unaffected sibs tested in 6/7 fam). The solute carrier (SLC) superfamily of transmembrane transporters - highly expressed in mammalian brain - is involved in exchange of amino-acids (AAs), nutrients, ions, neurotransmitters and metabolites etc across biological membranes with >100 SLC-encoding genes associated with NDDs. SLC38A3 specifically encodes SNAT3, a sodium-coupled neutral amino-acid transporter, principal transporter of Asn, His, Gln (precursor for GABA and glutamate), expressed in brain, liver, kidney, retina and pancreas. In the brain, it localizes to peri-synaptic astrocytes playing an important role in glutamate/GABA-glutamine cycle. While the pLoF variants are predicted to undergo NMD or result in non-functional protein, protein modelling suggested that missense ones affect protein activity or stability. Biochemical and metabolic screening was carried out for several individuals with plasma AAs reported normal (10/10), urinary OAs normal in 9/9, CSF AAs (incl. GABA/glutamine) normal in 2 sibs, CSF lactate normal in 1 indiv. studied. As discussed above plasma ammonia was elevated in 4/7 (2 fam), and 7/10 had elevated lactate and/or pyruvate (2/7). Untargeted metabolomic profiles performed in biofluids (plasma from 3 subjects, CSF:1, urine:1) were suggestive of altered AA and nitrogen metabolism. In particular, alterations in levels of AA known to be transported by SNAT3 were found. 676 molecules overall showed deviation in plasma samples, 630 in urine and 241 in CSF (albeit with no consistent pattern). Perturbations in several biochemical pathways were shown to occur (incl. Gln-,Asn- and His- pathways). Slc38a3-/- mice have reductions in brain glutamate and GABA neurotransmitters in homogenized brain tissue (GABA analytes being normal in plasma samples or the single CSF sample available from affected subjects). Snat3-deficient mice had elevation of plasma urea and normal ammonia levels (urea was low in all human samples and ranged from -2 to -3.5 SD in plasma, ammonia was elevated in 4/7). Slc38a3-/- mice have impaired growth, lethargy and ataxic gait, altered plasma AAs, normal glutamine in plasma with abundance in brain and exhibit early lethality. Plasma AAs were normal in 4 affected individuals, impaired growth observed in 4 and gait impairment was observed in 9/10. Hypoglycemia, previously reported in Slc38a3-/- mice, was not observed in any of the patients although this is presumably explained by diet/feeding intervals with abnormalities in pentose phosphate pathway in one individual hypothesized to be reflective of abn. glucose metabolism. The human phenotypes of microcephaly and seizures were not observed in mice. For mouse studies PMIDs cited by the authors : 27362266, 26490457. There is currently no SLC38A3-related phenotype reported in OMIM. In G2P this gene is incl. in the DD panel (biallelic, confidence: strong, SLC38A3-associated epileptic encephalopathy). SLC38A3 is listed among the primary ID genes in SysID. In PanelApp Australia, SLC38A3 is included with green rating in the epilepsy, ID and microcephaly panels. Consider inclusion with green rating (10 individuals, 7 families, 7 variants, role of SLCs and SLC38A3, alterations in AA/nitrogen metabolism etc) or amber rating (if discordances with mouse model considered). Please consider inclusion in other panels e.g. for microcephaly, CC abnormalities, metabolic disorders, etc. Sources: Literature, Other
30 Mar 2022	Intellectual disability v3.1529	SLC38A3	Konstantinos Varvagiannis gene: SLC38A3 was added gene: SLC38A3 was added to Intellectual disability. Sources: Literature,Other Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC38A3 were set to 34605855 Phenotypes for gene: SLC38A3 were set to Infantile axial hypotonia; Global developmental delay; Intellectual disability; Seizures; Spasticity; Microcephaly; Cerebral atrophy; Cerebellar atrophy; Abnormality of the corpus callosum; Dysphagia; Constipation; Increased serum lactate; Hyperammonemia Penetrance for gene: SLC38A3 were set to Complete Review for gene: SLC38A3 was set to GREEN Added comment: Marafi et al (2021 - PMID: 34605855) describe the phenotype of 10 individuals, belonging to 7 families (6/7 consanguineous), harboring biallelic deleterious SLC38A3 variants. One subject (from fam3) was previously reported in the context of a larger cohort of consanguineous families investigated with exome sequencing (2017, PMID: 31130284). The phenotype overall corresponded to a DEE and features included axial hypotonia (10/10), severe global DD or ID (10/10), seizures (8/10, onset : 1w-15m, NOT observed in 2/10 aged 1y3m and 4y \| s. types: tonic-clonic in 3/8, tonic 2/8, focal 2/8 with secondary generalization, myoclonic 1/8, gelastic 1/8 \| EEG burst-suppression, hypsarrhythmia in few). Microcephaly was observed in (8/10) and was more commonly postnatal and/or progressive. Variable abnormalities were observed upon brain imaging incl. cerebral (5/10) or cerebellar atrophy (2/10) and abnormal CC (6/10), abnormal myelination for age (6/10). Other phenotypes included visual impairment (9/10), peripheral hypertonia (8/9) constipation (8/9) and dysphagia (7/9), FTT (4/8), movement disorder (3/10). Metabolic studies indicated (transient) elevation of lactate (7/8 - also pyruvate in 2) and elevated plasma ammonia (4/7). Individuals from the 1st family were investigated with ES, and the SLC38A3 splice site variant (NM_006841.6:c.855+1G>T) was the most likely candidate, additional SNVs not contributing to the NDD phenotype. Other affected subjects were ascertained through GeneMatcher/collaborations. In total, 3 different missense and 4 pLoF (1 fs, 2 nonsense, 1 splicing) variants were identified with individuals from 2 families being hmz or cmd htz for missense variants. Variants were absent/ultrarare with no homozygotes in public/in-house databases with several in silico predictions in favor of a deleterious effect. Regions of AOH (around SLC38A3/total) are provided for some individuals/families. Sanger sequencing was used for confirmation and segregation studies (apart from carrier parents in 7/7 fam, 11 unaffected sibs tested in 6/7 fam). The solute carrier (SLC) superfamily of transmembrane transporters - highly expressed in mammalian brain - is involved in exchange of amino-acids (AAs), nutrients, ions, neurotransmitters and metabolites etc across biological membranes with >100 SLC-encoding genes associated with NDDs. SLC38A3 specifically encodes SNAT3, a sodium-coupled neutral amino-acid transporter, principal transporter of Asn, His, Gln (precursor for GABA and glutamate), expressed in brain, liver, kidney, retina and pancreas. In the brain, it localizes to peri-synaptic astrocytes playing an important role in glutamate/GABA-glutamine cycle. While the pLoF variants are predicted to undergo NMD or result in non-functional protein, protein modelling suggested that missense ones affect protein activity or stability. Biochemical and metabolic screening was carried out for several individuals with plasma AAs reported normal (10/10), urinary OAs normal in 9/9, CSF AAs (incl. GABA/glutamine) normal in 2 sibs, CSF lactate normal in 1 indiv. studied. As discussed above plasma ammonia was elevated in 4/7 (2 fam), and 7/10 had elevated lactate and/or pyruvate (2/7). Untargeted metabolomic profiles performed in biofluids (plasma from 3 subjects, CSF:1, urine:1) were suggestive of altered AA and nitrogen metabolism. In particular, alterations in levels of AA known to be transported by SNAT3 were found. 676 molecules overall showed deviation in plasma samples, 630 in urine and 241 in CSF (albeit with no consistent pattern). Perturbations in several biochemical pathways were shown to occur (incl. Gln-,Asn- and His- pathways). Slc38a3-/- mice have reductions in brain glutamate and GABA neurotransmitters in homogenized brain tissue (GABA analytes being normal in plasma samples or the single CSF sample available from affected subjects). Snat3-deficient mice had elevation of plasma urea and normal ammonia levels (urea was low in all human samples and ranged from -2 to -3.5 SD in plasma, ammonia was elevated in 4/7). Slc38a3-/- mice have impaired growth, lethargy and ataxic gait, altered plasma AAs, normal glutamine in plasma with abundance in brain and exhibit early lethality. Plasma AAs were normal in 4 affected individuals, impaired growth observed in 4 and gait impairment was observed in 9/10. Hypoglycemia, previously reported in Slc38a3-/- mice, was not observed in any of the patients although this is presumably explained by diet/feeding intervals with abnormalities in pentose phosphate pathway in one individual hypothesized to be reflective of abn. glucose metabolism. The human phenotypes of microcephaly and seizures were not observed in mice. For mouse studies PMIDs cited by the authors : 27362266, 26490457. There is currently no SLC38A3-related phenotype reported in OMIM. In G2P this gene is incl. in the DD panel (biallelic, confidence: strong, SLC38A3-associated epileptic encephalopathy). SLC38A3 is listed among the primary ID genes in SysID. In PanelApp Australia, SLC38A3 is included with green rating in the epilepsy, ID and microcephaly panels. Consider inclusion with green rating (10 individuals, 7 families, 7 variants, role of SLCs and SLC38A3, alterations in AA/nitrogen metabolism etc) or amber rating (if discordances with mouse model considered). Please consider inclusion in other panels e.g. for microcephaly, CC abnormalities, metabolic disorders, etc. Sources: Literature, Other
29 Mar 2022	Renal ciliopathies v1.61	ZNF423	Arina Puzriakova reviewed gene: ZNF423: Rating: ; Mode of pathogenicity: None; Publications: 22863007, 32925911, 33323469; Phenotypes: Joubert syndrome 19, OMIM:614844, Nephronophthisis 14, OMIM:614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
29 Mar 2022	Skeletal dysplasia v2.190	ANO5	Sarah Leigh Tag Q1_22_MOI tag was added to gene: ANO5.
29 Mar 2022	DDG2P v2.65	ANO5	Sarah Leigh reviewed gene: ANO5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
29 Mar 2022	DDG2P v2.65	ALPL	Sarah Leigh reviewed gene: ALPL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
29 Mar 2022	Cystic kidney disease v2.37	ALG8	Sarah Leigh Publications for gene: ALG8 were set to 30135240; 28375157
29 Mar 2022	Cystic kidney disease v2.36	ALG8	Sarah Leigh reviewed gene: ALG8: Rating: ; Mode of pathogenicity: None; Publications: 15235028; Phenotypes: ; Mode of inheritance: None
29 Mar 2022	Polycystic liver disease v1.23	ALG8	Sarah Leigh reviewed gene: ALG8: Rating: ; Mode of pathogenicity: None; Publications: 15235028; Phenotypes: ; Mode of inheritance: None
29 Mar 2022	Intellectual disability v3.1529	ALG8	Sarah Leigh Publications for gene: ALG8 were set to 0
29 Mar 2022	Likely inborn error of metabolism v2.236	SPTLC1	Sarah Leigh Tag Q1_22_MOI tag was added to gene: SPTLC1.
29 Mar 2022	Likely inborn error of metabolism v2.236	SPTLC1	Sarah Leigh Added comment: Comment on mode of inheritance: There is no data to support that homozygous variants of SPTLC1 are associated with Neuropathy, hereditary sensory and autonomic, type IA, OMIM:162400. Therefore the MOI for this gene should be MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
29 Mar 2022	Likely inborn error of metabolism v2.236	SPTLC1	Sarah Leigh Mode of inheritance for gene: SPTLC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
29 Mar 2022	Undiagnosed metabolic disorders v1.516	SPTLC1	Sarah Leigh Mode of inheritance for gene: SPTLC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
29 Mar 2022	Undiagnosed metabolic disorders v1.515	SPTLC1	Sarah Leigh Publications for gene: SPTLC1 were set to 27604308; 20097765; 21618344; 20097765; 30420926
29 Mar 2022	Likely inborn error of metabolism v2.235	SPTLC1	Sarah Leigh Publications for gene: SPTLC1 were set to 27604308; 20097765; 21618344; 20097765; 30420926
29 Mar 2022	Likely inborn error of metabolism v2.234	SPTLC1	Sarah Leigh Deleted their comment
29 Mar 2022	Likely inborn error of metabolism v2.234	SPTLC1	Sarah Leigh Deleted their comment
29 Mar 2022	Likely inborn error of metabolism v2.234	SPTLC1	Sarah Leigh Deleted their comment
29 Mar 2022	Undiagnosed metabolic disorders v1.514	SPTLC1	Sarah Leigh Deleted their comment
29 Mar 2022	Undiagnosed metabolic disorders v1.514	SPTLC1	Sarah Leigh Deleted their comment
29 Mar 2022	Undiagnosed metabolic disorders v1.514	SPTLC1	Sarah Leigh Deleted their comment
28 Mar 2022	Intellectual disability v3.1528	ADAT3	Arina Puzriakova Phenotypes for gene: ADAT3 were changed from Mental retardation, autosomal recessive 36, 615286; MRT36 to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, OMIM:615286
28 Mar 2022	Early onset or syndromic epilepsy v2.504	ADAT3	Arina Puzriakova Phenotypes for gene: ADAT3 were changed from Mental retardation, autosomal recessive 36 615286 to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, OMIM:615286
28 Mar 2022	Extreme early-onset hypertension v1.15	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Neuropathy, hereditary sensory and autonomic, type II, 201300; Pseudohypoaldosteronism, type IIC, 614492 to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300; Pseudohypoaldosteronism, type IIC, OMIM:614492
28 Mar 2022	Renal tubulopathies v2.40	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Pseudohypoaldosteronism, type IIC, 614492 to Pseudohypoaldosteronism, type IIC, OMIM:614492
28 Mar 2022	Hereditary neuropathy or pain disorder v1.89	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Hereditary Sensory and Autonomic Neuropathy, Type II; Neuropathy, hereditary sensory and autonomic, type II, 201300; Pseudohypoaldosteronism, type IIC, 614492 to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300
28 Mar 2022	Hereditary neuropathy v1.443	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Hereditary Sensory and Autonomic Neuropathy, Type II; Pseudohypoaldosteronism, type IIC, 614492; Hereditary Sensory and Autonomic Neuropathy, Type II ; Neuropathy, hereditary sensory and autonomic, type II, 201300; Pseudohypoaldosteronism, type IIC, 614492 to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300
28 Mar 2022	Paroxysmal central nervous system disorders v1.43	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from HSAN 2; Neuropathy, hereditary sensory and autonomic, type II, 201300; Hereditary sensory and autonomic neuropathy type IIA to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300
28 Mar 2022	Familial dysautonomia v1.16	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Neuropathy, hereditary sensory and autonomic, type II 201300 to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300
28 Mar 2022	Pain syndromes v1.11	WNK1	Arina Puzriakova Phenotypes for gene: WNK1 were changed from Hereditary sensory and autonomic neuropathy type IIA; HSAN 2; Neuropathy, hereditary sensory and autonomic, type II, 201300 to Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300
28 Mar 2022	Early onset dystonia v1.113	TOR1A	Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441 to Dystonia-1, torsion, OMIM:128100; Arthrogryposis multiplex congenita 5, OMIM:618947
28 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.220	TOR1A	Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441 to Dystonia-1, torsion, OMIM:128100; Arthrogryposis multiplex congenita 5, OMIM:618947
28 Mar 2022	Early onset dystonia v1.112	TOR1A	Arina Puzriakova Added comment: Comment on mode of inheritance: Dystonia association with monoallelic variants is well-established with multiple cases reported worldwide (OMIM:128100). Biallelic variants cause a more severe phenotype of congenital arthrogryposis (OMIM:618947) and movement impairments including dystonia are also common (PMIDs: 29053766, 30244176). For this reason the MOI was updated from 'monoallelic' only to 'both mono- and biallelic (biallelic more severe)'.
28 Mar 2022	Early onset dystonia v1.112	TOR1A	Arina Puzriakova Mode of inheritance for gene: TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
28 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.219	TOR1A	Arina Puzriakova Publications for gene: TOR1A were set to 20301334; 11523564; 17503336; 20301665; 9288096; 16537570
28 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.218	TOR1A	Arina Puzriakova Tag Q1_22_MOI tag was added to gene: TOR1A.
28 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.218	TOR1A	Arina Puzriakova reviewed gene: TOR1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia-1, torsion, OMIM:128100, Arthrogryposis multiplex congenita 5, OMIM:618947; Mode of inheritance: None
28 Mar 2022	Intellectual disability v3.1527	TBXAS1	Arina Puzriakova Phenotypes for gene: TBXAS1 were changed from Ghosal hematodiaphyseal syndrome, OMIM:231095 to Ghosal hematodiaphyseal syndrome, OMIM:231095
28 Mar 2022	Intellectual disability v3.1527	TBXAS1	Arina Puzriakova Phenotypes for gene: TBXAS1 were changed from Ghosal hematodiaphyseal syndrome, 231095; ?Thromboxane synthase; deficiency, 614158 to Ghosal hematodiaphyseal syndrome, OMIM:231095
28 Mar 2022	Inherited bleeding disorders v1.165	TBXAS1	Arina Puzriakova Phenotypes for gene: TBXAS1 were changed from Ghosal syndrome to Ghosal hematodiaphyseal syndrome, OMIM:231095; ?Thromboxane synthase deficiency, OMIM:614158; Bleeding disorder, platelet-type, 14, OMIM:614158
28 Mar 2022	Bleeding and platelet disorders v1.36	TBXAS1	Arina Puzriakova Phenotypes for gene: TBXAS1 were changed from 231095 Ghosal hematodiaphyseal syndrome; 614158 ?Thromboxane synthase deficiency; 614158 ?Thromboxane synthase deficiency, 231095 Ghosal hematodiaphyseal syndrome to Ghosal hematodiaphyseal syndrome, OMIM:231095; ?Thromboxane synthase deficiency, OMIM:614158; Bleeding disorder, platelet-type, 14, OMIM:614158
28 Mar 2022	Hereditary ataxia with onset in adulthood v2.150	SPTBN2	Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from Spinocerebellar Ataxia, Dominant; Autosomal recessive spinocerebellar ataxia 14, 615386; Spinocerebellar ataxia, autosomal recessive 14; Spinocerebellar ataxia 5; Spinocerebellar ataxia 5, 600224; SPINOCEREBELLAR ATAXIA 5 (autosomal dominant); SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 14 to Spinocerebellar ataxia 5, OMIM:600224; Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
28 Mar 2022	Adult onset neurodegenerative disorder v2.269	SPTBN2	Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 14; Spinocerebellar Ataxia, Dominant; Spinocerebellar ataxia, autosomal recessive 14; SPINOCEREBELLAR ATAXIA 5 (autosomal dominant); Spinocerebellar ataxia 5 to Spinocerebellar ataxia 5, OMIM:600224; Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
28 Mar 2022	Cerebellar hypoplasia v1.62	SPTBN2	Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from Spinocerebellar ataxia 5 (AD); Spinocerebellar ataxia, autosomal recessive 14 (AR) to Spinocerebellar ataxia 5, OMIM:600224; Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
28 Mar 2022	Hereditary ataxia v1.300	SPTBN2	Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from Spinocerebellar ataxia 5; Spinocerebellar ataxia, autosomal recessive 14; Spinocerebellar Ataxia, Dominant; SPINOCEREBELLAR ATAXIA 5 (autosomal dominant); SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 14 to Spinocerebellar ataxia 5, OMIM:600224; Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
28 Mar 2022	Intellectual disability v3.1526	SPTBN2	Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from Spinocerebellar ataxia, autosomal recessive 14; MIM:615386; Developmental delay to Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
28 Mar 2022	Palmoplantar keratodermas v1.13	SLURP1	Arina Puzriakova Tag Q2_21_MOI tag was added to gene: SLURP1.
28 Mar 2022	Palmoplantar keratodermas v1.13	SLURP1	Arina Puzriakova reviewed gene: SLURP1: Rating: ; Mode of pathogenicity: None; Publications: 14756676; Phenotypes: Meleda disease, OMIM:248300; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
28 Mar 2022	Palmoplantar keratodermas v1.13	SLURP1	Arina Puzriakova Phenotypes for gene: SLURP1 were changed from Mal de Meleda to Meleda disease, OMIM:248300
28 Mar 2022	Peroxisomal disorders v1.16	SCP2	Zornitza Stark reviewed gene: SCP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 16685654, 26497993; Phenotypes: Leukoencephalopathy with dystonia and motor neuropathy, MIM#613724; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
27 Mar 2022	Early onset or syndromic epilepsy v2.503	CACNA2D1	Konstantinos Varvagiannis reviewed gene: CACNA2D1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35293990, 28097321; Phenotypes: Abnormal muscle tone, Feeding difficulties, Global developmental delay, Intellectual disability, Seizures, Microcephaly, Abnormality of the corpus callosum, Cerebral atrophy, Abnormality of movement, Cortical visual impairment, Pain insensitivity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
27 Mar 2022	Intellectual disability v3.1525	CACNA2D1	Konstantinos Varvagiannis gene: CACNA2D1 was added gene: CACNA2D1 was added to Intellectual disability. Sources: Literature,Other Mode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA2D1 were set to 35293990; 28097321 Phenotypes for gene: CACNA2D1 were set to Abnormal muscle tone; Feeding difficulties; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of the corpus callosum; Cerebral atrophy; Abnormality of movement; Cortical visual impairment; Pain insensitivity Penetrance for gene: CACNA2D1 were set to Complete Review for gene: CACNA2D1 was set to GREEN Added comment: Consider inclusion in the current panel with green rating. Recent report of 2 unrelated individuals with DEE due to biallelic CACNA2D1 variants. Both referred to neurology/genetics for hypotonia/severe DD prior to onset of seizures. One further individual with hypotonia and severe ID (seizures not discussed, age unknown). Gene with established role, encoding α2δ-1 subunit of Cav channels. Studies for the variants support loss-of-function as the underlying effect. Eventual contribution of monoallelic variants to NDD-phenotypes discussed (and put in question) in Ref [1] below. There is currently no phenotype for CACNA2D1 in OMIM/G2P. In SysID this gene is listed among the candidates for ID, based on a previous report. CACNA2D1 is not currently included in the ID/epilepsy panels in PanelApp Australia. See also relevant review in epilepsy panel (Dr. H. Lord). Please consider also inclusion in other panels (e.g. microcephaly, corpus callosum, movement disorders, etc). [1] ---- Dahimene et al (2022 - PMID: 35293990) describe the phenotype of 2 unrelated individuals with biallelic CACNA2D1 variants. Overall, the phenotype corresponded to an early-onset DEE, characterized by abnormal muscle tone (axial hypotonia 2/2 with spasticity in extremities in 2/2), feeding difficulties (2/2), profound DD and ID (2/2), microcephaly (2/2 - approx. -2 SD in both), seizures (2/2 - 1st : onset 9m with absences and later generalized seizures, 2nd : onset 11m with hemi-clonic seizures and atypical absences). Other features included cortical visual impairment (2/2) and movement disorder (incl. choreiform movements 2/2, orofacial dyskinesia 2/2 and dystonic episodes 1/2). Brain MRI revealed corpus callosum anomalies (2/2) and cerebral atrophy (2/2). Both had echocardiography (abnormal in 1/2 - tiny PFO) and electrocardiography which was normal. Both exhibited insensibility to pain. Presentation is relevant to the current panel as first symptoms in the first 3 months with severe hypotonia and poor head control (2/2) with evaluation in neurology/genetics preceding onset of seizures in both. Trio ES was performed for both individuals and their (healthy) parents and revealed homozygosity for a fs variant in the first [NM_000722.3:c.818_822dup / p.(Ser275Asnfs13)] and compound htz for a fs and a missense variant [c.13_23dup / p.(Leu9Alafs5) and c.626G>A / p.(Gly209Asp)] in the second affected individual, respectively. Eventual additional variants were not discussed. Previous investigations are only provided for the 2nd and were all normal (karyotype, CMA, 15q methylation, epilepsy/neurometabolic gene panels). Voltage-gated calcium channels are heteromultimers comprising different subunits incl. an alpha-1 (α1), α2δ (alpha-2/delta), beta (β) and gamma (γ). CACNA2D1 is one of the 4 genes (CACNA2D1-4) encoding the alpha-2/delta subunit. Its product is post-translationally processed into 2 peptides, an alpha-2 and a delta subunit, held by a disulfide bond. Biallelic variants in CACNA2D2 - also encoding an alpha-2/delta subunit - cause cerebellar atrophy with seizures and variable developmental delay (# 618501). Variant studies support loss-of-function effect for the studied variants, notably by NMD for the fs one, and severe impairment of the Cav2 channel function for the missense one : - CACNA2D1 mRNA was reduced to 6-9% compared with control in fibroblasts from the 1st individual. mRNA levels for the 2nd subject were similar to control. - Quantification of the protein in whole-cell lysates from fibroblasts revealed lower α2δ levels compared to control (10-12% and 31-38% applying to the 1st and 2nd individual). - CACNA2D3 mRNA levels in fibroblasts from the 2nd patient were 2-7x higher compared to the 1st or controls suggesting a possible compensatory effect. CACNA2D2/4 mRNA levels were too low for quantification. - Gly209 lies within the gabapentin and amino-acid binding pocket and this residue is invariable in CACNA2D1/CACNA2D2 in all vertebrates and paralogs. - Transfection of tsA-201 cells with either WT or G209D HA-tagged α2δ revealed reduced cell surface expression for this missense variant (~80, for biotinylated form ~86%). - In tsA-201 cells transfected with HA-tagged Cav2.2/β1b and either α2δ-1-WT, no α2δ-1 or α2δ-1-G209D, WT resulted in increased 13x currents with no increase applying to G209D (or in absence of α2δ). Plasma membrane expression of double (GFP/HA) tagged Cav2.2 was increased upon co-expression with WT α2δ-1 which was not the case for α2δ-1-G209D. - In hippocampal neurons, double (GFP/HA)-tagged Cav2.2 could not be detected at the cell surface in the presence of α2δ-1-G209D (or no α2δ) in contrast with strong expression in presence of α2δ-1-WT. α2δ-1-G209D did not promote trafficking of Cav2.2 into hippocampal neurites, as indicated by reduced signals for both HA and GFP (for cell surface and total Cav2.2 respectively). - Co-expression of double (GFP/HA) tagged Cav2.2 with β1b and either HA-α2δ-1-WT or HA-α2δ-1-G209D in tsA-201 cells, revealed reduced complex formation of G209D with Cav2.2 Co-immunoprecipitated HA-α2δ-1-G209D had higher molecular weight compared to HA-α2δ-1-WT which suggests that α2δ-1-G209D remains as the uncleaved immature form (probably in the ER). Mouse model (several Refs in text): Mild cardiac phenotype and reduced ventricular myocyte Ca current density was observed in hmz ko mice. Similarly to the insensibility to pain human phenotype, mice had delayed neuropathic pain-related responses. Overexpression of a2δ-1 resulted in epileptiform EEG and behavioral arrest, overall supporting a critical role of α2δ-1 for mouse brain. The authors underscore that the parents of both patients (htz carriers) were healthy and review previous literature for association of monoallelic variants with epilepsy, ID and arrhythmogenic disorders (in suppl.) [Refs not here reviewed]. As for the NDD phenotype, CACNA2D1 is within a previously defined small region of overlap for 7q21.11 microdeletions associated with ID+/-epilepsy. The same study did not reveal de novo SNVs in any of the 3 contained genes within this SRO (HGF, CACNA2D1, PCLO) in 4293 patients with NDD [cited PMID: 28240412]. A frameshift variant (c.2625del) was identified in a 13-yo girl with infantile spasms and normal intelligence [cited PMID: 25877686]. A 1-bp insertion (c.659-2_659-1insT / not studied at the mRNA level) was identified in another 14-yo female with ID and epilepsy [cited PMID: 34356170]. The authors state that the phenotype (/differences) of these individuals as well as presence of pLoF CACNA2D1 variants in gnomAD [still pLI of 1] put in question pathogenicity of monoallelic variants for these phenotypes. The role of heterozygous missense variants described in relation to arrhythmogenic disorders is also discussed extensively (some downgraded to LB/VUS, others having a relatively high MAF and presence of 1-2 homozygotes in gnomAD). [2] ---- In an article cited by SysID for CACNA2D1 (2017 - PMID: 28097321), Reuter et al studied with WES and autozygosity mapping individuals with NDD belonging to consanguineous families. As in eTables1/3, a male - single affected individual born to consanguineous parents from Turkey (MR150) - was investigated by singleton ES. This individual was homozygous for a missense CACNA2D1 SNV [NM_000722.2:c.1514C>T;p.(Thr505Ile)]. Prior investigations are unavailable (although individuals with previously known P/LP CNVs were excluded). The phenotype - briefly reported - included hypotonia, severe ID, stereotypic behaviors, inguinal hernia and omphalocele. Presence of seizures was not commented on. The age of this individual was not reported. Sources: Literature, Other
25 Mar 2022	Intellectual disability v3.1525	ACTL6B	Arina Puzriakova Phenotypes for gene: ACTL6B were changed from Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 76, OMIM:618468; Intellectual developmental disorder with severe speech and ambulation defects, OMIM:618470
25 Mar 2022	Early onset or syndromic epilepsy v2.503	ACTL6B	Arina Puzriakova Phenotypes for gene: ACTL6B were changed from Epileptic encephalopathy, early infantile, 76, 618468; Global developmental delay; Intellectual disability; Seizures; Spasticity; epileptic encephalopathy to Developmental and epileptic encephalopathy 76, OMIM:618468
25 Mar 2022	Childhood onset hereditary spastic paraplegia v2.131	ACER3	Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v1.227
25 Mar 2022	Childhood onset hereditary spastic paraplegia v2.131	ACER3	Arina Puzriakova gene: ACER3 was added gene: ACER3 was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature,Expert Review Amber Q1_22_rating tags were added to gene: ACER3. Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACER3 were set to 26792856; 32816236; 34281620 Phenotypes for gene: ACER3 were set to Leukodystrophy, progressive, early childhood-onset, OMIM:617762
25 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.218	ACER3	Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v1.227
25 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.218	ACER3	Arina Puzriakova gene: ACER3 was added gene: ACER3 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review Amber,Literature Q1_22_rating tags were added to gene: ACER3. Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACER3 were set to 26792856; 32816236; 34281620 Phenotypes for gene: ACER3 were set to Leukodystrophy, progressive, early childhood-onset, OMIM:617762
25 Mar 2022	Intellectual disability v3.1524	ACER3	Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v1.227
25 Mar 2022	Intellectual disability v3.1524	ACER3	Arina Puzriakova gene: ACER3 was added gene: ACER3 was added to Intellectual disability. Sources: Expert Review Amber,Literature Q1_22_rating tags were added to gene: ACER3. Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACER3 were set to 26792856; 32816236; 34281620 Phenotypes for gene: ACER3 were set to Leukodystrophy, progressive, early childhood-onset, OMIM:617762
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.227	ACER3	Arina Puzriakova Classified gene: ACER3 as Amber List (moderate evidence)
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.227	ACER3	Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene Green on this panel at the next GMS review - now at least 5 unrelated families reported with homozygous variants (PMIDs: 26792856; 32816236; 34281620). Phenotypes that are consistent amongst all affected individuals comprise of developmental regression (motor and cognitive), dystonia, spasticity, and leukodystrophy.
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.227	ACER3	Arina Puzriakova Gene: acer3 has been classified as Amber List (Moderate Evidence).
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.226	ACER3	Arina Puzriakova Publications for gene: ACER3 were set to 32816236; 26792856
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.225	ACER3	Arina Puzriakova Tag watchlist was removed from gene: ACER3. Tag Q1_22_rating tag was added to gene: ACER3.
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.225	ACER3	Arina Puzriakova reviewed gene: ACER3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34281620; Phenotypes: Leukodystrophy, progressive, early childhood-onset, OMIM:617762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
25 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.225	ACER3	Arina Puzriakova Phenotypes for gene: ACER3 were changed from ?Leukodystrophy, progressive, early childhood-onset, OMIM:617762 to Leukodystrophy, progressive, early childhood-onset, OMIM:617762
25 Mar 2022	Intellectual disability v3.1523	TRAPPC10	Konstantinos Varvagiannis reviewed gene: TRAPPC10: Rating: AMBER; Mode of pathogenicity: None; Publications: 35298461, 30167849; Phenotypes: Abnormal muscle tone, Global developmental delay, Intellectual disability, Microcephaly, Short stature, Gait disturbance; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
25 Mar 2022	Familial pulmonary fibrosis v1.28	ACD	Arina Puzriakova Tag watchlist_moi tag was added to gene: ACD.
25 Mar 2022	Familial pulmonary fibrosis v1.28	ACD	Arina Puzriakova Mode of inheritance for gene: ACD was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
25 Mar 2022	Familial pulmonary fibrosis v1.27	ACD	Arina Puzriakova Classified gene: ACD as Green List (high evidence)
25 Mar 2022	Familial pulmonary fibrosis v1.27	ACD	Arina Puzriakova Added comment: Comment on list classification: This gene was approved by the NHS Genomic Medicine Service, rated green on the 'Pulmonary fibrosis familial' GMS panel with 'monoallelic' inheritance. Therefore the MOI and rating on this panel was also updated accordingly and the 'watchlist' tag was removed. Added 'watchlist_MOI' tag to ensure monitoring of biallelic variants as currently no evidence linking these to PF is available but may emerge in the future.
25 Mar 2022	Familial pulmonary fibrosis v1.27	ACD	Arina Puzriakova Gene: acd has been classified as Green List (High Evidence).
25 Mar 2022	Familial pulmonary fibrosis v1.26	ACD	Arina Puzriakova Tag watchlist was removed from gene: ACD.
25 Mar 2022	Pulmonary fibrosis familial v0.6	ACD	Arina Puzriakova Phenotypes for gene: ACD were changed from Dyskeratosis congenita, autosomal dominant, OMIM:6 to Dyskeratosis congenita, autosomal dominant, OMIM:616553
25 Mar 2022	Pulmonary fibrosis familial v0.5	ACD	Arina Puzriakova Publications for gene: ACD were set to
25 Mar 2022	Cholestasis v1.106	AP1S1	Ivone Leong Classified gene: AP1S1 as Red List (low evidence)
25 Mar 2022	Cholestasis v1.106	AP1S1	Ivone Leong Added comment: Comment on list classification: Demoted from Amber to Red based on expert review by Miranda Durkie (Genetics).
25 Mar 2022	Cholestasis v1.106	AP1S1	Ivone Leong Gene: ap1s1 has been classified as Red List (Low Evidence).
25 Mar 2022	Cholestasis v1.105	AP1S1	Ivone Leong Tag Q2_21_rating was removed from gene: AP1S1.
25 Mar 2022	Pancreatitis v2.16	CEL	Ivone Leong Classified gene: CEL as Amber List (moderate evidence)
25 Mar 2022	Pancreatitis v2.16	CEL	Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber based on expert review by Miranda Durkie. This gene is associated with a phenotype in OMIM but not in Gene2Phenotype.
25 Mar 2022	Pancreatitis v2.16	CEL	Ivone Leong Gene: cel has been classified as Amber List (Moderate Evidence).
25 Mar 2022	Pancreatitis v2.15	CEL	Ivone Leong Phenotypes for gene: CEL were changed from to Hereditary Pancreatitis
25 Mar 2022	Pancreatitis v2.14	CEL	Ivone Leong Publications for gene: CEL were set to 29233499; 28881607; 28500240; 27802312; 27650499; 27773618; 26946345; 25774637; 23770712
25 Mar 2022	Pancreatitis v2.13	CEL	Ivone Leong Mode of inheritance for gene: CEL was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
24 Mar 2022	Early onset or syndromic epilepsy v2.502	RELN	Sarah Leigh Phenotypes for gene: RELN were changed from {Epilepsy, familial temporal lobe, 7} 616436 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; {Epilepsy, familial temporal lobe, 7}, OMIM:616436
24 Mar 2022	Early onset or syndromic epilepsy v2.501	RELN	Sarah Leigh Publications for gene: RELN were set to 26046367
24 Mar 2022	Intellectual disability v3.1523	SLC12A5	Sarah Leigh reviewed gene: SLC12A5: Rating: ; Mode of pathogenicity: None; Publications: 24928908, 24668262, 26333769; Phenotypes: Developmental and epileptic encephalopathy 34, OMIM:616645; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
24 Mar 2022	Intellectual disability v3.1523	SLC12A5	Sarah Leigh Publications for gene: SLC12A5 were set to 24668262; 26333769
24 Mar 2022	Intellectual disability v3.1522	SLC12A5	Sarah Leigh Tag Q1_22_MOI tag was added to gene: SLC12A5.
24 Mar 2022	Intellectual disability v3.1522	SLC12A5	Sarah Leigh Phenotypes for gene: SLC12A5 were changed from FEBRILE SEIZURES to Developmental and epileptic encephalopathy 34, OMIM; 616645
24 Mar 2022	Intellectual disability v3.1521	SLC12A5	Sarah Leigh Publications for gene: SLC12A5 were set to 24668262
24 Mar 2022	Brain channelopathy v1.78	KCNMA1	Sarah Leigh reviewed gene: KCNMA1: Rating: ; Mode of pathogenicity: None; Publications: 29545233, 27567911; Phenotypes: Cerebellar atrophy, developmental delay, and seizures, OMIM:617643; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
24 Mar 2022	Paroxysmal central nervous system disorders v1.42	KCNMA1	Sarah Leigh Tag Q1_22_MOI tag was added to gene: KCNMA1.
24 Mar 2022	Paroxysmal central nervous system disorders v1.42	KCNMA1	Sarah Leigh reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29545233, 27567911; Phenotypes: Cerebellar atrophy, developmental delay, and seizures, OMIM:617643; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
24 Mar 2022	Paroxysmal central nervous system disorders v1.42	KCNMA1	Sarah Leigh Publications for gene: KCNMA1 were set to 15937479; 26195193
23 Mar 2022	Adult onset neurodegenerative disorder v2.268	CACNA1A_CAG	Louise Daugherty reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	CACNA1A_CAG	Louise Daugherty reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ATXN10_ATTCT	Louise Daugherty reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
23 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.539	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from Immunodeficiency 14,615513; Combined immunodeficiency; Unclassified antibody deficiency; Activated PI3K-delta syndrome (APDS); sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia; Severe bacterial infections; decreased or absent pro-B cells, EBV; Predominantly Antibody Deficiencies to Immunodeficiency 14A, autosomal dominant, OMIM:615513; Immunodeficiency 14B, autosomal recessive, OMIM:619281; Combined immunodeficiency; Activated PI3K-delta syndrome (APDS); Predominantly Antibody Deficiencies; Sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia; Severe bacterial infections
23 Mar 2022	COVID-19 research v1.118	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from Combined immunodeficiency; Activated PI3K-delta syndrome (APDS); Unclassified antibody deficiency; decreased or absent pro-B cells, EBV; Predominantly Antibody Deficiencies; sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia; Severe bacterial infections; Immunodeficiency 14,615513 to Immunodeficiency 14A, autosomal dominant, OMIM:615513; Immunodeficiency 14B, autosomal recessive, OMIM:619281; Combined immunodeficiency; Activated PI3K-delta syndrome (APDS); Predominantly Antibody Deficiencies; Sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia; Severe bacterial infections
23 Mar 2022	Gastrointestinal epithelial barrier disorders v1.71	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14B, autosomal recessive, OMIM:619281
23 Mar 2022	Gastrointestinal epithelial barrier disorders v1.70	PIK3CD	Arina Puzriakova Mode of inheritance for gene: PIK3CD was changed from to BIALLELIC, autosomal or pseudoautosomal
23 Mar 2022	Respiratory ciliopathies including non-CF bronchiectasis v1.56	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from Immunodeficiency 14, 615513; Bronchiectasis to Immunodeficiency 14A, autosomal dominant, OMIM:615513; Bronchiectasis
23 Mar 2022	Non-CF bronchiectasis v1.27	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14A, autosomal dominant, OMIM:615513
23 Mar 2022	Infantile enterocolitis & monogenic inflammatory bowel disease v1.37	PIK3CD	Arina Puzriakova Phenotypes for gene: PIK3CD were changed from PI3K activation syndrome; Immunodeficiency 14 615513 to Immunodeficiency 14A, autosomal dominant, OMIM:615513
23 Mar 2022	Early onset or syndromic epilepsy v2.500	CACNA2D1	Helen Lord changed review comment from: Dahimne et al, 2022, 35293990 - two unrelated patients with biallelic CACNA2D1 variants - trio exome sequencing - identified by gene matcher. Patient 1: homozygous fs variant c.818_821dup p.(Ser275fs) - healthy parents het carriers. Patient 2: compound het for a fs c.13_23dup p.(Leu9fs) and a missense variant c.626G>A p.(Gly209Asp) - parents healthy carriers of each of the variants. Both individuals show a highly consistent phenotype, corresponding to DEE - microcephalic, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia and cortical visual impairement. Brain imaging showed corpus callosum hypoplasia and progressive volume loss in both. Both patients also showed insensitivity to pain. Looking at mRNA level in patient fibroblasts in both patients showed it was reduced to 6-9% compared to control fibroblasts. Also data suggest the fs variants result in LOF. Gly209 - this Gly is important for maintaining a 3-strand-beta-sheet-stability and simultaneously provididn ga critial turn in the structure and is absoloutely invariant in both CACNA2D1 and CACNA2D2 orthologs in all vertebrates and paralogs and predecessors from low invertebrates. Functional work on the missense change shows it disrupts plasma membrane a2d-1 expression by 86.2% compared to wt. It abolishes the ability of a2d-1 to promote Cav2.2 currents, it does not promote Cav2.2 cell surface expression or trafficking in hippocampal neurons and it shows reduced complex formation with Cav2.2 and limited proteolytic cleavage. Suggests the HA-a2b-1 with the G209D variant remains largely as the uncleaved imaature form, indicating that it probably remains in the endoplasmic reticulum - suggests LOF effect. Sources: NHS GMS; to: Dahimne et al, 2022, 35293990 - two unrelated patients with biallelic CACNA2D1 variants - trio exome sequencing - identified by gene matcher. Patient 1: homozygous fs variant c.818_821dup p.(Ser275fs) - healthy parents het carriers. Patient 2: compound het for a fs c.13_23dup p.(Leu9fs) and a missense variant c.626G>A p.(Gly209Asp) - parents healthy carriers of each of the variants. Both individuals show a highly consistent phenotype, corresponding to DEE - microcephalic, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia and cortical visual impairement. Brain imaging showed corpus callosum hypoplasia and progressive volume loss in both. Both patients also showed insensitivity to pain. Looking at mRNA level in patient fibroblasts in both patients showed it was reduced to 6-9% compared to control fibroblasts. Also data suggest the fs variants result in LOF. Gly209 - this Gly is important for maintaining a 3-strand-beta-sheet-stability and simultaneously providing a critial turn in the structure and is absoloutely invariant in both CACNA2D1 and CACNA2D2 orthologs in all vertebrates and paralogs and predecessors from low invertebrates. Functional work on the missense change shows it disrupts plasma membrane a2d-1 expression by 86.2% compared to wt. It abolishes the ability of a2d-1 to promote Cav2.2 currents, it does not promote Cav2.2 cell surface expression or trafficking in hippocampal neurons and it shows reduced complex formation with Cav2.2 and limited proteolytic cleavage. Suggests the HA-a2b-1 with the G209D variant remains largely as the uncleaved imaature form, indicating that it probably remains in the endoplasmic reticulum - suggests LOF effect. Sources: NHS GMS
23 Mar 2022	Early onset or syndromic epilepsy v2.500	CACNA2D1	Helen Lord changed review comment from: Dahimne et al, 2022, 35293990 - two unrelated patients with biallelic CACNA2D1 variants - trio exome sequencing - identified by gene matcher. Patient 1: homozygous fs variant c.818_821dup p.(Ser275fs) - healthy parents het carriers. Patient 2: compound het for a fs c.13_23dup p.(Leu9fs) and a missense variant c.626G>A p.(Gly209Asp) - parents healthy carriers of each of the variants. Both individuals show a highly conssitent phenotype, corresponding to DEE - microcephalic, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia and cortical visual impairement. Brain imaging showed corpus callosum hypoplasia and progressive volume loss in both. Both patients also showed insensitivty to apin Looking at mRNA level in patient fibroblasts in both pTIWNTS showed it was reduced to 6-9% compared to control fibroblasts. Also data suggest the fs variants result in LOF. Gly209 - this Gly is importnat for maintaining a 3-strand-beta-sheet-stability and simultaneously provididn ga critial turn in the structure and is absoloutely invariant in both CACNA2D1 and CACNA2D2 orthologs in all vertebrates and paralogs and predecessors from low invertebrates. Functional work on the missense change shows it disrupts plasma membrane a2d-1 expression by 86.2% compared to wt. It abolshes the ability of a2d-1 to promote Cav2.2 currents, it does not promote Cav2.2 cell surface exprtession or trafficking in hippocampal neurons and it shows reduced complex formation with Cav2.2 and limited proteolytic cleavage. Suggests the HA-a2b-1 with the G209D variant remians largely as the uncleaved imaature form, indicating that it probably remains in the endoplasmic reticulum - suggests LOF effect. Sources: NHS GMS; to: Dahimne et al, 2022, 35293990 - two unrelated patients with biallelic CACNA2D1 variants - trio exome sequencing - identified by gene matcher. Patient 1: homozygous fs variant c.818_821dup p.(Ser275fs) - healthy parents het carriers. Patient 2: compound het for a fs c.13_23dup p.(Leu9fs) and a missense variant c.626G>A p.(Gly209Asp) - parents healthy carriers of each of the variants. Both individuals show a highly consistent phenotype, corresponding to DEE - microcephalic, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia and cortical visual impairement. Brain imaging showed corpus callosum hypoplasia and progressive volume loss in both. Both patients also showed insensitivity to pain. Looking at mRNA level in patient fibroblasts in both patients showed it was reduced to 6-9% compared to control fibroblasts. Also data suggest the fs variants result in LOF. Gly209 - this Gly is important for maintaining a 3-strand-beta-sheet-stability and simultaneously provididn ga critial turn in the structure and is absoloutely invariant in both CACNA2D1 and CACNA2D2 orthologs in all vertebrates and paralogs and predecessors from low invertebrates. Functional work on the missense change shows it disrupts plasma membrane a2d-1 expression by 86.2% compared to wt. It abolishes the ability of a2d-1 to promote Cav2.2 currents, it does not promote Cav2.2 cell surface expression or trafficking in hippocampal neurons and it shows reduced complex formation with Cav2.2 and limited proteolytic cleavage. Suggests the HA-a2b-1 with the G209D variant remains largely as the uncleaved imaature form, indicating that it probably remains in the endoplasmic reticulum - suggests LOF effect. Sources: NHS GMS
23 Mar 2022	Early onset or syndromic epilepsy v2.500	CACNA2D1	Helen Lord gene: CACNA2D1 was added gene: CACNA2D1 was added to Genetic epilepsy syndromes. Sources: NHS GMS Mode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA2D1 were set to 35293990 Phenotypes for gene: CACNA2D1 were set to Early onset developmental epilepsy Review for gene: CACNA2D1 was set to AMBER Added comment: Dahimne et al, 2022, 35293990 - two unrelated patients with biallelic CACNA2D1 variants - trio exome sequencing - identified by gene matcher. Patient 1: homozygous fs variant c.818_821dup p.(Ser275fs) - healthy parents het carriers. Patient 2: compound het for a fs c.13_23dup p.(Leu9fs) and a missense variant c.626G>A p.(Gly209Asp) - parents healthy carriers of each of the variants. Both individuals show a highly conssitent phenotype, corresponding to DEE - microcephalic, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia and cortical visual impairement. Brain imaging showed corpus callosum hypoplasia and progressive volume loss in both. Both patients also showed insensitivty to apin Looking at mRNA level in patient fibroblasts in both pTIWNTS showed it was reduced to 6-9% compared to control fibroblasts. Also data suggest the fs variants result in LOF. Gly209 - this Gly is importnat for maintaining a 3-strand-beta-sheet-stability and simultaneously provididn ga critial turn in the structure and is absoloutely invariant in both CACNA2D1 and CACNA2D2 orthologs in all vertebrates and paralogs and predecessors from low invertebrates. Functional work on the missense change shows it disrupts plasma membrane a2d-1 expression by 86.2% compared to wt. It abolshes the ability of a2d-1 to promote Cav2.2 currents, it does not promote Cav2.2 cell surface exprtession or trafficking in hippocampal neurons and it shows reduced complex formation with Cav2.2 and limited proteolytic cleavage. Suggests the HA-a2b-1 with the G209D variant remians largely as the uncleaved imaature form, indicating that it probably remains in the endoplasmic reticulum - suggests LOF effect. Sources: NHS GMS
23 Mar 2022	Early onset or syndromic epilepsy v2.500	KCNC2	Helen Lord reviewed gene: KCNC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314505; Phenotypes: epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
22 Mar 2022	Fetal anomalies v1.844	MYH6	Ivone Leong Tag Q1_22_MOI tag was added to gene: MYH6.
22 Mar 2022	Corneal abnormalities v1.12	TGFBI	Ivone Leong Tag Q1_22_MOI tag was added to gene: TGFBI.
22 Mar 2022	Intellectual disability v3.1520	ZNF292	Rachel Challis reviewed gene: ZNF292: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31723249; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
21 Mar 2022	Bleeding and platelet disorders v1.35	F7	Arina Puzriakova commented on gene: F7
21 Mar 2022	Inherited bleeding disorders v1.164	F12	Arina Puzriakova commented on gene: F12
21 Mar 2022	Bleeding and platelet disorders v1.35	F12	Arina Puzriakova commented on gene: F12
21 Mar 2022	Vascular skin disorders v1.48	F12	Arina Puzriakova commented on gene: F12
21 Mar 2022	COVID-19 research v1.117	F12	Arina Puzriakova Phenotypes for gene: F12 were changed from hereditary angioedema; Angioedema, Hereditary, Type III to Angioedema, hereditary, 3, OMIM:610618
21 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.538	F12	Arina Puzriakova Phenotypes for gene: F12 were changed from Angioedema, Hereditary, Type III; hereditary angioedema to Angioedema, hereditary, 3, OMIM:610618
21 Mar 2022	Pancreatitis v2.12	CEL	Miranda Durkie reviewed gene: CEL: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 16369531, PMID: 34850019; Phenotypes: Hereditary Pancreatitis, Diabetes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
21 Mar 2022	Cholestasis v1.105	AP1S1	Miranda Durkie reviewed gene: AP1S1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32306098; Phenotypes: Congenital diarrhoea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
20 Mar 2022	Early onset or syndromic epilepsy v2.500	NAPB	Tracy Lester gene: NAPB was added gene: NAPB was added to Genetic epilepsy syndromes. Sources: NHS GMS Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAPB were set to 28097321; 33189936; 26235277; 21040848 Phenotypes for gene: NAPB were set to Early infantile epileptic encephalopathy Penetrance for gene: NAPB were set to unknown Review for gene: NAPB was set to GREEN Added comment: Three cases reported with early infantile epileptic encepahlopathy and with homozygous LOF variants in this gene. Null mice also develop severe recurrent epileptic seizures from day 11, followed by ataxia. Sufficient evidence to be considered as green gene on the epilepsy and ID panels, autosomal recessive inheritance only. Sources: NHS GMS
19 Mar 2022	Intellectual disability v3.1520	PAN2	Konstantinos Varvagiannis gene: PAN2 was added gene: PAN2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAN2 were set to 29620724; https://doi.org/10.1038/s41431-022-01077-y Phenotypes for gene: PAN2 were set to Global developmental delay; Intellectual disability; Sensorineural hearing impairment; Abnormality of the genitourinary system; Abnormality of the cardiovascular system; Abnormality of blood and blood-forming tissues; EEG abnormality; Seizures; Anorectal anomaly; Abnormality of the skeletal system; Abnormality of the eye; Abnormality of head or neck Penetrance for gene: PAN2 were set to Complete Review for gene: PAN2 was set to AMBER Added comment: 1. Maddirevula et al (2018 - PMID: 29620724) first reported on the phenotype associated with biallelic pathogenic variants in PAN2. This concerned a male (15DG2222) born to consanguineous parents and exhibiting MCA, dysmorphic features and global DD (age of 34 m). Features incl. imperforate anus, metopic craniosynostosis, scoliosis, CHD (PFO, PDA, VSD), renal anomalies (duplicated collecting system) and abnormalities of the eye (posterior embryotoxon, maculopathy). As the other 411 individuals from the cohort, the child had 1st-tier testing genetic testing using a dysmorphology/skeletal dysplasia panel of 296 genes. Subsequent autozygome analysis (Axiom genotyping platform) was used to identify ROH (authors state "segregating within the family", in pedigree the proband was the single affected person and single child). WES revealed a PAN2 indel. [NM_001166279.1:c.3162delC / p.(Ser1055Profs4)]. There were no additional studies. Role of PAN2 and animal models discussed as below. --- 2. Reuter et al. (2022 - https://doi.org/10.1038/s41431-022-01077-y) describe the phenotype of 5 additional individuals - from 3 unrelated families (2 consanguineous) - harboring biallelic PAN2 variants. The authors review the phenotype of the previously described case. Features included DD (6/6), ID (4/5 with relevant age in the mild-moderate range, 1/5 had borderline IF), sensorineural hearing loss (5/6) and incompletely penetrant congenital anomalies of the heart (4/6 - TOF, septal defects, Ao root dilat), urinary malformations (4/6 - hypoplasia/agenesis, anovesical fistula), ophthalmological anomalies (2/6 - Rieger, posterior embryotoxon, etc). EEG anomalies or seizures were noted in 4/6. Craniofacial feat. in >=2/6 included cleft palate/bifid uvula, ptosis, hypertelorism, abn. of the nose, low-set ears, short neck. There was no comprehensive evaluation for skeletal dysplasia despite short stature/skeletal anomalies in multiple individuals. Hematological anomalies were reported in 2, possibly explained by another concurrent diagnosis (of GSD) in one individual. WGS was performed for 1 individual, and WES for 4 members of the 2nd family and the proband in the 3rd. ROH identified in all 3 families (1 non-consanguineous but from the same region of Italy) are mentioned in the suppl. Sanger sequencing for parents and affected/unaffected sibs was mentioned for the 2 families with solo WGS/WES. One individual had a dual - previously established - diagnosis (of SLC37A4-related GSD) not related to his NDD. There were no other candidate variants except for VUS or variants in 'genes of uncertain significance'. The majority of mammalian mature mRNAs have polyA tails, added during RNA processing. PAN2 encodes a subunit of the Pan2-Pan3 deadenylation complex which shortens mRNA 3' polyA tails, regulating mRNA stability/translation efficiency. Specifically Pan2 is the catalytic subunit, while the interaction with Pan3 mediates efficient mRNA binding. Deadenylation in cytoplasm is mostly carried out by the Pan2-Pan3 or Ccr4-Not compexes. While perturbations of mRNA metabolism/decay are established causes of NDD and ID. In particular, monoallelic variants in genes of Ccr4-Not complex (inc. CNOT1/2/3) already causative of NDDs. All affected individuals were homozygous for pLoF PAN2 variants, namely (NM_001166279.2): c.2335G>T / p.(Glu779) [Fam1], c.3408dupT / p.(Glu1137*) [Fam2], c.574-2A>G / p.? [Fam3]. Variants were absent from gnomAD (where PAN2 has a pLI:0.94, o/e:0.19). There were no variant studies performed. The splicing variant is predicted in silico to abolish the splice-acceptor site, with in-frame skippling of ex5 which codes a repeat within the WD40 domain. Previous studies in yeast have shown that this domain is important for sensing the length of the polyA tail, with absence of this domain resulting in impaired deadenylation of 90A tails (similarly to complete Pan2 del) [cited PMID: 31104843]. Overall PAN2 loss-of-function is thought to be the underlying disease mechanism. Partial functional redundancy of Pan2/Pan3 (initiation of deadenylation) and Ccr4-Not complexes (further shortening of polyA) is speculated to mitigate consequences of PAN2 LoF in humans. In yeast Pan2Δ, Ccr4Δ and Pan2Δ/Ccr4Δ have been studied with more severe phenotypes in double mutants where ability to shorten mRNA polyA tails was abolished [cited PMID:11239395]. In yeast extracts lacking Pan2p and Pan3p, transcripts were polyadenylated to >90-200 adenosines [cited PMID: 9774670] Mouse mutants (MGI:1918984) had increased heart weight, increased eosinophil cell number while homozygosity for a stopgain allele (by ENU mutagenesis) was shown to result in embyonic lethality. Finally, given the presence of thrombocytopenia and anemia in 3 individuals (2 families) as well as the link between mRNA deadenylation and telomere disease, telomere length analyses from WGS data were performed (TelSeq/Expansion Hunter dn), but there was no evidence for telomeric shortening. --- Currently, there is no PAN2-related phenotype in OMIM/G2P/SysID/PanelApp Australia. --- Consider inclusion in the ID panel with amber rating [>3 individuals/families/variants, though variant studies not performed (NMD/splicing) and authors of 2nd study recognize possibility of additional/concurrent diagnoses in individuals from consanguineous families, possibility of missed dn variants due to singleton WGS/WES in 2 fam. Also the presumed deadenylation defect not studied to date]. Please consider adding this gene to other panels - eg. for sens. hearing loss (5/6 - 3 fam), urinary tract anomalies (4/6 - 4 fam), congenital (4/6 - 3fam), anorectal malformations (2/6 - 2 families, incl. fistula or imperforate anus), clefting (2/6 - 1 fam), hematological disorders, etc. For the time being, not added in epilepsy panel as some individuals had only EEG anomalies, few had also clinical seizures not necessarily requiring treatment. Sources: Literature
19 Mar 2022	Hereditary neuropathy or pain disorder v1.88	PCYT2	Dmitrijs Rots gene: PCYT2 was added gene: PCYT2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to PMID: 35243002 Review for gene: PCYT2 was set to AMBER Added comment: Two brother with axonal neuropathy reported in PMID: 35243002. In the same study, after reviewing previously published cases, other individuals (2/10) had sensory deficit / neuropathy: "Of 5 previously reported adult patients (age range of 20–59 years),2-6 nerve conduction studies were performed in 2 of them and reported as normal.3,4 Clinically, one of them had hypopallesthesia of the ankles,4 and the other had loss of vibration sense in the lower limbs and mild loss of proprioception in the feet". Sources: Literature
19 Mar 2022	Rhabdomyolysis and metabolic muscle disorders v1.78	FDX2	Dmitrijs Rots reviewed gene: FDX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35079622; Phenotypes: ; Mode of inheritance: None
18 Mar 2022	Intellectual disability v3.1520	HIST1H4C	Konstantinos Varvagiannis reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 28920961, 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1, #619758; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
18 Mar 2022	Intellectual disability v3.1520	HIST1H4J	Konstantinos Varvagiannis reviewed gene: HIST1H4J: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 31804630, 35202563; Phenotypes: ?Tessadori-van Haaften neurodevelopmental syndrome 2, #619759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
18 Mar 2022	Intellectual disability v3.1520	HIST1H4D	Konstantinos Varvagiannis gene: HIST1H4D was added gene: HIST1H4D was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HIST1H4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4D were set to 35202563 Phenotypes for gene: HIST1H4D were set to Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face Penetrance for gene: HIST1H4D were set to Complete Mode of pathogenicity for gene: HIST1H4D was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: HIST1H4D was set to AMBER Added comment: Histone H4 is a core component of the nucleosome, the basic repeating unit of eukaryotic chromatin. Each nucleosome consists of ~150 bp of DNA wrapped around a histone octamer. Each histone octamer is composed of 2 copies of each of the histones H2A, H2B, H3, H4. This organization is important for DNA replication, transcription and repair. There are 14 canonical histone H4 genes in the human genome, which despite being different at the nucleotide level encode an identical protein. These cluster in 3 genomic loci. Their transcription is independently regulated with differing expression during brain development and in human tissues. Histone H4 forms a dimer with H3 (which however has variant isoforms linked to specific cellular processes). Pathogenic variants in genes encoding H4 have been reported in several individuals. Irrrespective of the gene for H4 involved, all patients presented with highly overlapping features, DD and ID being universal. Available reports to date concern : - H4C3/HIST1H4C (9 subjects - PMID: 28920961, 35202563), - H4C11/HIST1H4J (1 subject - PMID: 31804630, 35202563), - H4C4/HIST1H4D (1 subject - PMID:35202563), - H4C5/HIST1H4E (17 subjects - PMID: 35202563), - H4C6/HIST1H4F (1 subject - PMID: 35202563), - H4C9/HIST1H4I (3 subjects - PMID: 35202563). Variants in all cases were missense SNVs, occurring (in almost all cases) as dn variants and affecting the same residue in the same and/or different H4 genes (details for clusters below). Eg. Arg45Cys was a recurrent variant for H4C5 (>=7 subjects), while variants affecting Arg40 have been reported in H4C4, H4C5, H4C9, H4C11 (7 subjects overall). Zebrafish studies for all genes reported have included most - if not all - patient variants and recapitulate features observed in affected individuals (head size/structure and growth). Additional studies specificaly for H4C3/HIST1H4C have been performed in patient fibroblasts (demonstrating among others transcriptional dysregulation) and zebrafish (accumulation of DSBs, increased apoptosis in head/tail, abn. cell cycle progression). Note that the nomenclature for variants - at the protein level - used in literature commonly takes into consideration cleavage of Met1, thus the numbering may not correspond to the HGVS one. Relevant entries exist in OMIM, G2P and SysID only for H4C3/HIST1H4C (Tessadori-van Haaften neurodevelopmental syndrome 1, #619758) and H4C11/HIST1H4J (?Tessadori-van Haaften neurodevelopmental syndrome 2, #619759) but not for other genes. Rating in PanelApp Australia - ID Panel : HIST1H4C Green, H4J Amber, H4D Amber, H4E Green, H4F Amber, H4I Green. Please consider inclusion in other possibly relevant panels (microcephaly, short stature/FTT, etc). ------ Initial work from Tessadori et al (incl. DDD study, 2017 - PMID:28920961) identified monoallelic missense SNVs affecting the same residue of H4C3 (HIST1H4C), in 3 individuals from 2 families. [c.274A>C/ HGVS p.(Lys92Gln) dn in 1 subject and c.275A>C/ HGVS p.(Lys92Arg) inherited from unaffected mosaic parent]. Individuals from both families having relevant age had intellectual disability (2/2 - 2 families). Other features incl. growth delay (3/3) and microcephaly (3/3). Expression of the variants in zebrafish severely affected structural development recapitulating the patient phenotypes (microcephaly and short stature). RNA sequencing in fibroblasts from 2 unrelated patients and a control, revealed that expression of H4C3 variants was similar to wt. The authors estimated that ~8% of H4 cDNA molecules contained the variant. LC-MS/MS analysis suggested that the mutant protein was present in nucleosomes at a level of 1-2% while RNA-seq identified 115 differential expressed genes, with enrichment for relevant procedures (chr. organization, histone binding, DNA packaging, nucleosomal organization, cell cycle). Post-translational modifications of Lys92 (H4K91) are highly conserved and have been previously associated with processes from chromatin assembly , DNA damage sensitivity, etc. Post-translational marks on Lys92 (K91) were absent in patient derived cells as a result of each variant. Zebrafish models for both variants were suggestive for accumulation of double strand breaks (DSBs) more visible in heads and tails of larvae. Embryos expressing mutants displayed increased apoptosis in head and tail. Additional studies in larvae were suggestive of abnormal cell cycle progression (rel. increase in cellls in S/G2/M phase, increased occurrence of activated CHK2 with p53 stabilization) applying to both variants studied. ------ In a subsequent publication, Tessadori et al. (2020 - PMID: 31804630) described the phenotype of a 14 y.o. boy harboring a dn heterozygous missense H4C11 (HIST1H4J) variant following trio-ES [c.274A>G / HGVS p.(Lys92Glu)]. Features incl. profound ID, microcephaly, short stature with some dysmorphic features (uplsanting p-f, hypertelorism, etc). Previous work-up was normal/non-diagnostic and incl. FMR1, MECP2 and a CMA showing an inherited 207 kb CNV involving KCNV1. Upon mRNA microinjection in zebrafish embryos - either for wt or for Lys92Glu HIST1H4J - effect for wt was very mild. Lys92Glu expression led to defective development of head structures (brain, eyes), faulty body axis growth and dysmorphic tail reproducing the microcephaly and short stature phenotype. This was similar to previous zebrafish studies for HIS1H4C variants (above). ------ Tessadori et al. (2022 - PMID: 35202563) describe 29 *additional individuals with de novo missense variants in genes encoding H4, namely: - H4C3 (HIST1H4C/N=6 subjects), - H4C11 (HIST1H4J/N=1), - H4C4 (HIST1H4D/N=1), - H4C5 (HIST1H4E/N=17), - H4C6 (HIST1H4F/N=1), - H4C9 (HIST1H4I/N=3). All individuals, exhibited DD and ID (29/29). Other features incl. hypotonia (10/29), seizures (5/29), autism (5/29), ataxia (4/29). Abnormal growth incl. progressive microcephaly (2/19 prenatal, 20/29 postnatal onset), short stature/FTT (each 11/29). Few had skeletal features (craniosynostosis 2/29, abn. digits 4/29, vertebral 4/29). Some had visual (17/28) or hearing impairment (7/29). Facial features incl. hypertelorism (5/29), upslanting p-f (3/29), broad nasal tip (11/29), thin upper lip (4/29) and teeth anomalies (6/29 - notably gap between central incisors). The authors state that the cohort was collected with trio WES but also after data sharing via Genematcher / DECIPHER. Identified variants were in all cases missense and de novo, the latter either by trio WES or Sanger sequencing of parents. Previous work-up or presence of additional variants are not discussed. At the protein level 10 aa were affected, 6 of which recurrently within the same gene (Arg45, His75, Lys91, Tyr98) as well among several genes for H4 (Pro32, Arg40). Variants lied within two clusters, one corresponding to the α-helix of H4 (reported variants affected Lys31 - Arg45) important for DNA contacts, interactions with H3 and histone chaperones. The other within the core of nucleosome (reported patient variants : His75-Tyr98) with important strucural contact between H3-H4 dimer and histone chaperones. There were no detectable genotype-phenotype patterns separating individual H4 genes or protein regions. Of note, variability was observed even among 7 individuals with the same dn H4C5 variant (Arg45Cys). All variants were absent from control databases incl. gnomAD and affected residues conserved through to S. cerevisiae. Substitutions affecting Arg45 and Gly94 and His75 have been studied previously with effect in growth/fitness/chromatin remodeling/DNA damage repair depending on variant (5 studies cited). Zebrafish embryos at the 1 cell stage were injected with mRNA encoding either wt or identified variants, the latter inducing significant developmental defects with the exception of Pro32Ala (H4C3) and Arg40Cys (H4C5, H4C11). For Pro32Ala and Arg40Cys however, the strong recurrence in this cohort supports pathogenicity. A dosage dependent effect was observed for 2 variants. H4 genes appear to be tolerant to both missense and loss-of-function variation (the latter even in homozygous form) suggesting a dominant effect of the variants. ------ [RefSeqs : H4C3/HIST1H4C - NM_0035242.4 \| H4C4/HIST1H4D - NM_003539.4 \| H4C5/HIST1H4E - NM_003545.3 \| H4C6/HIST1H4F - NM_003540.4 \| H4C9/HIST1H4I - NM_003495.2 \| H4C11/HIST1H4J - NM_021968.4 // Variants at the protein level above are according to the HGVS nomenclature. However as the N-terminal methionine is cleaved, numbering relative to the mature peptide has also been used in publications eg. p.Pro33Ala HGVS corresponding to Pro32Ala] Sources: Literature
18 Mar 2022	Intellectual disability v3.1520	HIST1H4E	Konstantinos Varvagiannis gene: HIST1H4E was added gene: HIST1H4E was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4E were set to 35202563 Phenotypes for gene: HIST1H4E were set to Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face Penetrance for gene: HIST1H4E were set to unknown Mode of pathogenicity for gene: HIST1H4E was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: HIST1H4E was set to GREEN Added comment: Histone H4 is a core component of the nucleosome, the basic repeating unit of eukaryotic chromatin. Each nucleosome consists of ~150 bp of DNA wrapped around a histone octamer. Each histone octamer is composed of 2 copies of each of the histones H2A, H2B, H3, H4. This organization is important for DNA replication, transcription and repair. There are 14 canonical histone H4 genes in the human genome, which despite being different at the nucleotide level encode an identical protein. These cluster in 3 genomic loci. Their transcription is independently regulated with differing expression during brain development and in human tissues. Histone H4 forms a dimer with H3 (which however has variant isoforms linked to specific cellular processes). Pathogenic variants in genes encoding H4 have been reported in several individuals. Irrrespective of the gene for H4 involved, all patients presented with highly overlapping features, DD and ID being universal. Available reports to date concern : - H4C3/HIST1H4C (9 subjects - PMID: 28920961, 35202563), - H4C11/HIST1H4J (1 subject - PMID: 31804630, 35202563), - H4C4/HIST1H4D (1 subject - PMID:35202563), - H4C5/HIST1H4E (17 subjects - PMID: 35202563), - H4C6/HIST1H4F (1 subject - PMID: 35202563), - H4C9/HIST1H4I (3 subjects - PMID: 35202563). Variants in all cases were missense SNVs, occurring (in almost all cases) as dn variants and affecting the same residue in the same and/or different H4 genes (details for clusters below). Eg. Arg45Cys was a recurrent variant for H4C5 (>=7 subjects), while variants affecting Arg40 have been reported in H4C4, H4C5, H4C9, H4C11 (7 subjects overall). Zebrafish studies for all genes reported have included most - if not all - patient variants and recapitulate features observed in affected individuals (head size/structure and growth). Additional studies specificaly for H4C3/HIST1H4C have been performed in patient fibroblasts (demonstrating among others transcriptional dysregulation) and zebrafish (accumulation of DSBs, increased apoptosis in head/tail, abn. cell cycle progression). Note that the nomenclature for variants - at the protein level - used in literature commonly takes into consideration cleavage of Met1, thus the numbering may not correspond to the HGVS one. Relevant entries exist in OMIM, G2P and SysID only for H4C3/HIST1H4C (Tessadori-van Haaften neurodevelopmental syndrome 1, #619758) and H4C11/HIST1H4J (?Tessadori-van Haaften neurodevelopmental syndrome 2, #619759) but not for other genes. Rating in PanelApp Australia - ID Panel : HIST1H4C Green, H4J Amber, H4D Amber, H4E Green, H4F Amber, H4I Green. Please consider inclusion in other possibly relevant panels (microcephaly, short stature/FTT, etc). ------ Initial work from Tessadori et al (incl. DDD study, 2017 - PMID:28920961) identified monoallelic missense SNVs affecting the same residue of H4C3 (HIST1H4C), in 3 individuals from 2 families. [c.274A>C/ HGVS p.(Lys92Gln) dn in 1 subject and c.275A>C/ HGVS p.(Lys92Arg) inherited from unaffected mosaic parent]. Individuals from both families having relevant age had intellectual disability (2/2 - 2 families). Other features incl. growth delay (3/3) and microcephaly (3/3). Expression of the variants in zebrafish severely affected structural development recapitulating the patient phenotypes (microcephaly and short stature). RNA sequencing in fibroblasts from 2 unrelated patients and a control, revealed that expression of H4C3 variants was similar to wt. The authors estimated that ~8% of H4 cDNA molecules contained the variant. LC-MS/MS analysis suggested that the mutant protein was present in nucleosomes at a level of 1-2% while RNA-seq identified 115 differential expressed genes, with enrichment for relevant procedures (chr. organization, histone binding, DNA packaging, nucleosomal organization, cell cycle). Post-translational modifications of Lys92 (H4K91) are highly conserved and have been previously associated with processes from chromatin assembly , DNA damage sensitivity, etc. Post-translational marks on Lys92 (K91) were absent in patient derived cells as a result of each variant. Zebrafish models for both variants were suggestive for accumulation of double strand breaks (DSBs) more visible in heads and tails of larvae. Embryos expressing mutants displayed increased apoptosis in head and tail. Additional studies in larvae were suggestive of abnormal cell cycle progression (rel. increase in cellls in S/G2/M phase, increased occurrence of activated CHK2 with p53 stabilization) applying to both variants studied. ------ In a subsequent publication, Tessadori et al. (2020 - PMID: 31804630) described the phenotype of a 14 y.o. boy harboring a dn heterozygous missense H4C11 (HIST1H4J) variant following trio-ES [c.274A>G / HGVS p.(Lys92Glu)]. Features incl. profound ID, microcephaly, short stature with some dysmorphic features (uplsanting p-f, hypertelorism, etc). Previous work-up was normal/non-diagnostic and incl. FMR1, MECP2 and a CMA showing an inherited 207 kb CNV involving KCNV1. Upon mRNA microinjection in zebrafish embryos - either for wt or for Lys92Glu HIST1H4J - effect for wt was very mild. Lys92Glu expression led to defective development of head structures (brain, eyes), faulty body axis growth and dysmorphic tail reproducing the microcephaly and short stature phenotype. This was similar to previous zebrafish studies for HIS1H4C variants (above). ------ Tessadori et al. (2022 - PMID: 35202563) describe 29 *additional individuals with de novo missense variants in genes encoding H4, namely: - H4C3 (HIST1H4C/N=6 subjects), - H4C11 (HIST1H4J/N=1), - H4C4 (HIST1H4D/N=1), - H4C5 (HIST1H4E/N=17), - H4C6 (HIST1H4F/N=1), - H4C9 (HIST1H4I/N=3). All individuals, exhibited DD and ID (29/29). Other features incl. hypotonia (10/29), seizures (5/29), autism (5/29), ataxia (4/29). Abnormal growth incl. progressive microcephaly (2/19 prenatal, 20/29 postnatal onset), short stature/FTT (each 11/29). Few had skeletal features (craniosynostosis 2/29, abn. digits 4/29, vertebral 4/29). Some had visual (17/28) or hearing impairment (7/29). Facial features incl. hypertelorism (5/29), upslanting p-f (3/29), broad nasal tip (11/29), thin upper lip (4/29) and teeth anomalies (6/29 - notably gap between central incisors). The authors state that the cohort was collected with trio WES but also after data sharing via Genematcher / DECIPHER. Identified variants were in all cases missense and de novo, the latter either by trio WES or Sanger sequencing of parents. Previous work-up or presence of additional variants are not discussed. At the protein level 10 aa were affected, 6 of which recurrently within the same gene (Arg45, His75, Lys91, Tyr98) as well among several genes for H4 (Pro32, Arg40). Variants lied within two clusters, one corresponding to the α-helix of H4 (reported variants affected Lys31 - Arg45) important for DNA contacts, interactions with H3 and histone chaperones. The other within the core of nucleosome (reported patient variants : His75-Tyr98) with important strucural contact between H3-H4 dimer and histone chaperones. There were no detectable genotype-phenotype patterns separating individual H4 genes or protein regions. Of note, variability was observed even among 7 individuals with the same dn H4C5 variant (Arg45Cys). All variants were absent from control databases incl. gnomAD and affected residues conserved through to S. cerevisiae. Substitutions affecting Arg45 and Gly94 and His75 have been studied previously with effect in growth/fitness/chromatin remodeling/DNA damage repair depending on variant (5 studies cited). Zebrafish embryos at the 1 cell stage were injected with mRNA encoding either wt or identified variants, the latter inducing significant developmental defects with the exception of Pro32Ala (H4C3) and Arg40Cys (H4C5, H4C11). For Pro32Ala and Arg40Cys however, the strong recurrence in this cohort supports pathogenicity. A dosage dependent effect was observed for 2 variants. H4 genes appear to be tolerant to both missense and loss-of-function variation (the latter even in homozygous form) suggesting a dominant effect of the variants. ------ [RefSeqs : H4C3/HIST1H4C - NM_0035242.4 \| H4C4/HIST1H4D - NM_003539.4 \| H4C5/HIST1H4E - NM_003545.3 \| H4C6/HIST1H4F - NM_003540.4 \| H4C9/HIST1H4I - NM_003495.2 \| H4C11/HIST1H4J - NM_021968.4 // Variants at the protein level above are according to the HGVS nomenclature. However as the N-terminal methionine is cleaved, numbering relative to the mature peptide has also been used in publications eg. p.Pro33Ala HGVS corresponding to Pro32Ala] Sources: Literature
18 Mar 2022	Intellectual disability v3.1520	HIST1H4F	Konstantinos Varvagiannis gene: HIST1H4F was added gene: HIST1H4F was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HIST1H4F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4F were set to 35202563 Phenotypes for gene: HIST1H4F were set to Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face Penetrance for gene: HIST1H4F were set to unknown Mode of pathogenicity for gene: HIST1H4F was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: HIST1H4F was set to AMBER Added comment: Histone H4 is a core component of the nucleosome, the basic repeating unit of eukaryotic chromatin. Each nucleosome consists of ~150 bp of DNA wrapped around a histone octamer. Each histone octamer is composed of 2 copies of each of the histones H2A, H2B, H3, H4. This organization is important for DNA replication, transcription and repair. There are 14 canonical histone H4 genes in the human genome, which despite being different at the nucleotide level encode an identical protein. These cluster in 3 genomic loci. Their transcription is independently regulated with differing expression during brain development and in human tissues. Histone H4 forms a dimer with H3 (which however has variant isoforms linked to specific cellular processes). Pathogenic variants in genes encoding H4 have been reported in several individuals. Irrrespective of the gene for H4 involved, all patients presented with highly overlapping features, DD and ID being universal. Available reports to date concern : - H4C3/HIST1H4C (9 subjects - PMID: 28920961, 35202563), - H4C11/HIST1H4J (1 subject - PMID: 31804630, 35202563), - H4C4/HIST1H4D (1 subject - PMID:35202563), - H4C5/HIST1H4E (17 subjects - PMID: 35202563), - H4C6/HIST1H4F (1 subject - PMID: 35202563), - H4C9/HIST1H4I (3 subjects - PMID: 35202563). Variants in all cases were missense SNVs, occurring (in almost all cases) as dn variants and affecting the same residue in the same and/or different H4 genes (details for clusters below). Eg. Arg45Cys was a recurrent variant for H4C5 (>=7 subjects), while variants affecting Arg40 have been reported in H4C4, H4C5, H4C9, H4C11 (7 subjects overall). Zebrafish studies for all genes reported have included most - if not all - patient variants and recapitulate features observed in affected individuals (head size/structure and growth). Additional studies specificaly for H4C3/HIST1H4C have been performed in patient fibroblasts (demonstrating among others transcriptional dysregulation) and zebrafish (accumulation of DSBs, increased apoptosis in head/tail, abn. cell cycle progression). Note that the nomenclature for variants - at the protein level - used in literature commonly takes into consideration cleavage of Met1, thus the numbering may not correspond to the HGVS one. Relevant entries exist in OMIM, G2P and SysID only for H4C3/HIST1H4C (Tessadori-van Haaften neurodevelopmental syndrome 1, #619758) and H4C11/HIST1H4J (?Tessadori-van Haaften neurodevelopmental syndrome 2, #619759) but not for other genes. Rating in PanelApp Australia - ID Panel : HIST1H4C Green, H4J Amber, H4D Amber, H4E Green, H4F Amber, H4I Green. Please consider inclusion in other possibly relevant panels (microcephaly, short stature/FTT, etc). ------ Initial work from Tessadori et al (incl. DDD study, 2017 - PMID:28920961) identified monoallelic missense SNVs affecting the same residue of H4C3 (HIST1H4C), in 3 individuals from 2 families. [c.274A>C/ HGVS p.(Lys92Gln) dn in 1 subject and c.275A>C/ HGVS p.(Lys92Arg) inherited from unaffected mosaic parent]. Individuals from both families having relevant age had intellectual disability (2/2 - 2 families). Other features incl. growth delay (3/3) and microcephaly (3/3). Expression of the variants in zebrafish severely affected structural development recapitulating the patient phenotypes (microcephaly and short stature). RNA sequencing in fibroblasts from 2 unrelated patients and a control, revealed that expression of H4C3 variants was similar to wt. The authors estimated that ~8% of H4 cDNA molecules contained the variant. LC-MS/MS analysis suggested that the mutant protein was present in nucleosomes at a level of 1-2% while RNA-seq identified 115 differential expressed genes, with enrichment for relevant procedures (chr. organization, histone binding, DNA packaging, nucleosomal organization, cell cycle). Post-translational modifications of Lys92 (H4K91) are highly conserved and have been previously associated with processes from chromatin assembly , DNA damage sensitivity, etc. Post-translational marks on Lys92 (K91) were absent in patient derived cells as a result of each variant. Zebrafish models for both variants were suggestive for accumulation of double strand breaks (DSBs) more visible in heads and tails of larvae. Embryos expressing mutants displayed increased apoptosis in head and tail. Additional studies in larvae were suggestive of abnormal cell cycle progression (rel. increase in cellls in S/G2/M phase, increased occurrence of activated CHK2 with p53 stabilization) applying to both variants studied. ------ In a subsequent publication, Tessadori et al. (2020 - PMID: 31804630) described the phenotype of a 14 y.o. boy harboring a dn heterozygous missense H4C11 (HIST1H4J) variant following trio-ES [c.274A>G / HGVS p.(Lys92Glu)]. Features incl. profound ID, microcephaly, short stature with some dysmorphic features (uplsanting p-f, hypertelorism, etc). Previous work-up was normal/non-diagnostic and incl. FMR1, MECP2 and a CMA showing an inherited 207 kb CNV involving KCNV1. Upon mRNA microinjection in zebrafish embryos - either for wt or for Lys92Glu HIST1H4J - effect for wt was very mild. Lys92Glu expression led to defective development of head structures (brain, eyes), faulty body axis growth and dysmorphic tail reproducing the microcephaly and short stature phenotype. This was similar to previous zebrafish studies for HIS1H4C variants (above). ------ Tessadori et al. (2022 - PMID: 35202563) describe 29 *additional individuals with de novo missense variants in genes encoding H4, namely: - H4C3 (HIST1H4C/N=6 subjects), - H4C11 (HIST1H4J/N=1), - H4C4 (HIST1H4D/N=1), - H4C5 (HIST1H4E/N=17), - H4C6 (HIST1H4F/N=1), - H4C9 (HIST1H4I/N=3). All individuals, exhibited DD and ID (29/29). Other features incl. hypotonia (10/29), seizures (5/29), autism (5/29), ataxia (4/29). Abnormal growth incl. progressive microcephaly (2/19 prenatal, 20/29 postnatal onset), short stature/FTT (each 11/29). Few had skeletal features (craniosynostosis 2/29, abn. digits 4/29, vertebral 4/29). Some had visual (17/28) or hearing impairment (7/29). Facial features incl. hypertelorism (5/29), upslanting p-f (3/29), broad nasal tip (11/29), thin upper lip (4/29) and teeth anomalies (6/29 - notably gap between central incisors). The authors state that the cohort was collected with trio WES but also after data sharing via Genematcher / DECIPHER. Identified variants were in all cases missense and de novo, the latter either by trio WES or Sanger sequencing of parents. Previous work-up or presence of additional variants are not discussed. At the protein level 10 aa were affected, 6 of which recurrently within the same gene (Arg45, His75, Lys91, Tyr98) as well among several genes for H4 (Pro32, Arg40). Variants lied within two clusters, one corresponding to the α-helix of H4 (reported variants affected Lys31 - Arg45) important for DNA contacts, interactions with H3 and histone chaperones. The other within the core of nucleosome (reported patient variants : His75-Tyr98) with important strucural contact between H3-H4 dimer and histone chaperones. There were no detectable genotype-phenotype patterns separating individual H4 genes or protein regions. Of note, variability was observed even among 7 individuals with the same dn H4C5 variant (Arg45Cys). All variants were absent from control databases incl. gnomAD and affected residues conserved through to S. cerevisiae. Substitutions affecting Arg45 and Gly94 and His75 have been studied previously with effect in growth/fitness/chromatin remodeling/DNA damage repair depending on variant (5 studies cited). Zebrafish embryos at the 1 cell stage were injected with mRNA encoding either wt or identified variants, the latter inducing significant developmental defects with the exception of Pro32Ala (H4C3) and Arg40Cys (H4C5, H4C11). For Pro32Ala and Arg40Cys however, the strong recurrence in this cohort supports pathogenicity. A dosage dependent effect was observed for 2 variants. H4 genes appear to be tolerant to both missense and loss-of-function variation (the latter even in homozygous form) suggesting a dominant effect of the variants. ------ [RefSeqs : H4C3/HIST1H4C - NM_0035242.4 \| H4C4/HIST1H4D - NM_003539.4 \| H4C5/HIST1H4E - NM_003545.3 \| H4C6/HIST1H4F - NM_003540.4 \| H4C9/HIST1H4I - NM_003495.2 \| H4C11/HIST1H4J - NM_021968.4 // Variants at the protein level above are according to the HGVS nomenclature. However as the N-terminal methionine is cleaved, numbering relative to the mature peptide has also been used in publications eg. p.Pro33Ala HGVS corresponding to Pro32Ala] Sources: Literature
18 Mar 2022	Intellectual disability v3.1520	HIST1H4I	Konstantinos Varvagiannis gene: HIST1H4I was added gene: HIST1H4I was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4I were set to 35202563 Phenotypes for gene: HIST1H4I were set to Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face Penetrance for gene: HIST1H4I were set to unknown Mode of pathogenicity for gene: HIST1H4I was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: HIST1H4I was set to GREEN Added comment: Histone H4 is a core component of the nucleosome, the basic repeating unit of eukaryotic chromatin. Each nucleosome consists of ~150 bp of DNA wrapped around a histone octamer. Each histone octamer is composed of 2 copies of each of the histones H2A, H2B, H3, H4. This organization is important for DNA replication, transcription and repair. There are 14 canonical histone H4 genes in the human genome, which despite being different at the nucleotide level encode an identical protein. These cluster in 3 genomic loci. Their transcription is independently regulated with differing expression during brain development and in human tissues. Histone H4 forms a dimer with H3 (which however has variant isoforms linked to specific cellular processes). Pathogenic variants in genes encoding H4 have been reported in several individuals. Irrrespective of the gene for H4 involved, all patients presented with highly overlapping features, DD and ID being universal. Available reports to date concern : - H4C3/HIST1H4C (9 subjects - PMID: 28920961, 35202563), - H4C11/HIST1H4J (1 subject - PMID: 31804630, 35202563), - H4C4/HIST1H4D (1 subject - PMID:35202563), - H4C5/HIST1H4E (17 subjects - PMID: 35202563), - H4C6/HIST1H4F (1 subject - PMID: 35202563), - H4C9/HIST1H4I (3 subjects - PMID: 35202563). Variants in all cases were missense SNVs, occurring (in almost all cases) as dn variants and affecting the same residue in the same and/or different H4 genes (details for clusters below). Eg. Arg45Cys was a recurrent variant for H4C5 (>=7 subjects), while variants affecting Arg40 have been reported in H4C4, H4C5, H4C9, H4C11 (7 subjects overall). Zebrafish studies for all genes reported have included most - if not all - patient variants and recapitulate features observed in affected individuals (head size/structure and growth). Additional studies specificaly for H4C3/HIST1H4C have been performed in patient fibroblasts (demonstrating among others transcriptional dysregulation) and zebrafish (accumulation of DSBs, increased apoptosis in head/tail, abn. cell cycle progression). Note that the nomenclature for variants - at the protein level - used in literature commonly takes into consideration cleavage of Met1, thus the numbering may not correspond to the HGVS one. Relevant entries exist in OMIM, G2P and SysID only for H4C3/HIST1H4C (Tessadori-van Haaften neurodevelopmental syndrome 1, #619758) and H4C11/HIST1H4J (?Tessadori-van Haaften neurodevelopmental syndrome 2, #619759) but not for other genes. Rating in PanelApp Australia - ID Panel : HIST1H4C Green, H4J Amber, H4D Amber, H4E Green, H4F Amber, H4I Green. Please consider inclusion in other possibly relevant panels (microcephaly, short stature/FTT, etc). ------ Initial work from Tessadori et al (incl. DDD study, 2017 - PMID:28920961) identified monoallelic missense SNVs affecting the same residue of H4C3 (HIST1H4C), in 3 individuals from 2 families. [c.274A>C/ HGVS p.(Lys92Gln) dn in 1 subject and c.275A>C/ HGVS p.(Lys92Arg) inherited from unaffected mosaic parent]. Individuals from both families having relevant age had intellectual disability (2/2 - 2 families). Other features incl. growth delay (3/3) and microcephaly (3/3). Expression of the variants in zebrafish severely affected structural development recapitulating the patient phenotypes (microcephaly and short stature). RNA sequencing in fibroblasts from 2 unrelated patients and a control, revealed that expression of H4C3 variants was similar to wt. The authors estimated that ~8% of H4 cDNA molecules contained the variant. LC-MS/MS analysis suggested that the mutant protein was present in nucleosomes at a level of 1-2% while RNA-seq identified 115 differential expressed genes, with enrichment for relevant procedures (chr. organization, histone binding, DNA packaging, nucleosomal organization, cell cycle). Post-translational modifications of Lys92 (H4K91) are highly conserved and have been previously associated with processes from chromatin assembly , DNA damage sensitivity, etc. Post-translational marks on Lys92 (K91) were absent in patient derived cells as a result of each variant. Zebrafish models for both variants were suggestive for accumulation of double strand breaks (DSBs) more visible in heads and tails of larvae. Embryos expressing mutants displayed increased apoptosis in head and tail. Additional studies in larvae were suggestive of abnormal cell cycle progression (rel. increase in cellls in S/G2/M phase, increased occurrence of activated CHK2 with p53 stabilization) applying to both variants studied. ------ In a subsequent publication, Tessadori et al. (2020 - PMID: 31804630) described the phenotype of a 14 y.o. boy harboring a dn heterozygous missense H4C11 (HIST1H4J) variant following trio-ES [c.274A>G / HGVS p.(Lys92Glu)]. Features incl. profound ID, microcephaly, short stature with some dysmorphic features (uplsanting p-f, hypertelorism, etc). Previous work-up was normal/non-diagnostic and incl. FMR1, MECP2 and a CMA showing an inherited 207 kb CNV involving KCNV1. Upon mRNA microinjection in zebrafish embryos - either for wt or for Lys92Glu HIST1H4J - effect for wt was very mild. Lys92Glu expression led to defective development of head structures (brain, eyes), faulty body axis growth and dysmorphic tail reproducing the microcephaly and short stature phenotype. This was similar to previous zebrafish studies for HIS1H4C variants (above). ------ Tessadori et al. (2022 - PMID: 35202563) describe 29 *additional individuals with de novo missense variants in genes encoding H4, namely: - H4C3 (HIST1H4C/N=6 subjects), - H4C11 (HIST1H4J/N=1), - H4C4 (HIST1H4D/N=1), - H4C5 (HIST1H4E/N=17), - H4C6 (HIST1H4F/N=1), - H4C9 (HIST1H4I/N=3). All individuals, exhibited DD and ID (29/29). Other features incl. hypotonia (10/29), seizures (5/29), autism (5/29), ataxia (4/29). Abnormal growth incl. progressive microcephaly (2/19 prenatal, 20/29 postnatal onset), short stature/FTT (each 11/29). Few had skeletal features (craniosynostosis 2/29, abn. digits 4/29, vertebral 4/29). Some had visual (17/28) or hearing impairment (7/29). Facial features incl. hypertelorism (5/29), upslanting p-f (3/29), broad nasal tip (11/29), thin upper lip (4/29) and teeth anomalies (6/29 - notably gap between central incisors). The authors state that the cohort was collected with trio WES but also after data sharing via Genematcher / DECIPHER. Identified variants were in all cases missense and de novo, the latter either by trio WES or Sanger sequencing of parents. Previous work-up or presence of additional variants are not discussed. At the protein level 10 aa were affected, 6 of which recurrently within the same gene (Arg45, His75, Lys91, Tyr98) as well among several genes for H4 (Pro32, Arg40). Variants lied within two clusters, one corresponding to the α-helix of H4 (reported variants affected Lys31 - Arg45) important for DNA contacts, interactions with H3 and histone chaperones. The other within the core of nucleosome (reported patient variants : His75-Tyr98) with important strucural contact between H3-H4 dimer and histone chaperones. There were no detectable genotype-phenotype patterns separating individual H4 genes or protein regions. Of note, variability was observed even among 7 individuals with the same dn H4C5 variant (Arg45Cys). All variants were absent from control databases incl. gnomAD and affected residues conserved through to S. cerevisiae. Substitutions affecting Arg45 and Gly94 and His75 have been studied previously with effect in growth/fitness/chromatin remodeling/DNA damage repair depending on variant (5 studies cited). Zebrafish embryos at the 1 cell stage were injected with mRNA encoding either wt or identified variants, the latter inducing significant developmental defects with the exception of Pro32Ala (H4C3) and Arg40Cys (H4C5, H4C11). For Pro32Ala and Arg40Cys however, the strong recurrence in this cohort supports pathogenicity. A dosage dependent effect was observed for 2 variants. H4 genes appear to be tolerant to both missense and loss-of-function variation (the latter even in homozygous form) suggesting a dominant effect of the variants. ------ [RefSeqs : H4C3/HIST1H4C - NM_0035242.4 \| H4C4/HIST1H4D - NM_003539.4 \| H4C5/HIST1H4E - NM_003545.3 \| H4C6/HIST1H4F - NM_003540.4 \| H4C9/HIST1H4I - NM_003495.2 \| H4C11/HIST1H4J - NM_021968.4 // Variants at the protein level above are according to the HGVS nomenclature. However as the N-terminal methionine is cleaved, numbering relative to the mature peptide has also been used in publications eg. p.Pro33Ala HGVS corresponding to Pro32Ala] Sources: Literature
18 Mar 2022	Skeletal dysplasia v2.190	DVL2	Michael Oldridge gene: DVL2 was added gene: DVL2 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DVL2 were set to PMID: 35047859 Phenotypes for gene: DVL2 were set to autosomal dominant Robinow sydrome Penetrance for gene: DVL2 were set to Complete Mode of pathogenicity for gene: DVL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: DVL2 was set to GREEN Added comment: De novo fs variant in final exon of DVL2 identified in patient with clinical diagnosis of Robinow syndrome. This leads to a 103 residue missense tail extending beyond the WT stop codon. A number of similar fs variants have been identified in DVL1 and DVL3 leading to autosomal dominant Robinow syndrome; these variants also lead to extended missense tails and are therefore thought to act via a very specific gain of function mechanism (LOF variants in these genes do not lead to Robinow). DVL1, 2 and 3 share considerable homology (59-67%) and have overlapping function during development. Only reported in 1 case but the very specific nature of the mutation explains rareity. Should be tested as Green. Sources: Expert Review
18 Mar 2022	Ocular coloboma v1.46	RARB	Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as biallelic variants also cause disease.
18 Mar 2022	Ocular coloboma v1.46	RARB	Ivone Leong Mode of inheritance for gene: RARB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
18 Mar 2022	Anophthalmia or microphthalmia v1.45	SIX6	Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BIALLELIC, autosomal or pseudoautosomal". Review copied from Structural eye disease panel: "Aldamesh (2013) reported one family; Yariz (2015) one family; Patel (2018) one family), all three variants homozygous. Gallardo reported a heterozygous variant in a patient with bilateral microphthalmia, inherited from the unaffected father. This variant has now been reclassified on OMIM as VUS. Mode of inheritance should be changed. Nicola Ragge (Birmingham Women's and Children's NHS Foundation Hospital Trust), 19 Jun 2019"
18 Mar 2022	Anophthalmia or microphthalmia v1.45	SIX6	Ivone Leong Mode of inheritance for gene: SIX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
18 Mar 2022	Anophthalmia or microphthalmia v1.44	SIX6	Ivone Leong Phenotypes for gene: SIX6 were changed from Anophthalmia/Microphthalmia; Microphthalmia with cataract 2, 212550 to Optic disc anomalies with retinal and/or macular dystrophy, OMIM:212550
18 Mar 2022	Corneal dystrophy v1.10	TGFBI	Ivone Leong reviewed gene: TGFBI: Rating: ; Mode of pathogenicity: None; Publications: 31322463, 30830990, 32952948; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
18 Mar 2022	Corneal abnormalities v1.12	TGFBI	Ivone Leong Added comment: Comment on publications: New publications added: 31322463, 30830990, 32952948
18 Mar 2022	Corneal abnormalities v1.12	TGFBI	Ivone Leong Publications for gene: TGFBI were set to 11146721; 15531312; 16652336; 9780098; 9727509
18 Mar 2022	Corneal abnormalities v1.11	TGFBI	Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more severe disease)".
18 Mar 2022	Corneal abnormalities v1.11	TGFBI	Ivone Leong Mode of inheritance for gene: TGFBI was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
18 Mar 2022	Familial non syndromic congenital heart disease v1.75	MYH6	Ivone Leong Added comment: Comment on mode of inheritance: MOI change dfrom "BIALLELIC, autosomal or pseudoautosomal" to "Both Monoallelic and Biallelic" as Monoallelic variants also cause disease.
18 Mar 2022	Familial non syndromic congenital heart disease v1.75	MYH6	Ivone Leong Mode of inheritance for gene: MYH6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
18 Mar 2022	Fetal anomalies v1.844	MYH6	Ivone Leong reviewed gene: MYH6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
17 Mar 2022	Likely inborn error of metabolism v2.234	QARS	Sarah Leigh Mode of inheritance for gene: QARS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
17 Mar 2022	Likely inborn error of metabolism v2.233	QARS	Sarah Leigh Mode of inheritance for gene: QARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
17 Mar 2022	Likely inborn error of metabolism v2.233	QARS	Sarah Leigh Publications for gene: QARS were set to
17 Mar 2022	Mitochondrial disorders v2.95	GATC	Sarah Leigh Phenotypes for gene: GATC were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 42, OMIM:618839
17 Mar 2022	Mitochondrial disorders v2.94	GATC	Sarah Leigh Mode of inheritance for gene: GATC was changed from to BIALLELIC, autosomal or pseudoautosomal
17 Mar 2022	Likely inborn error of metabolism v2.232	GATC	Sarah Leigh Added comment: Comment on phenotypes: Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
17 Mar 2022	Likely inborn error of metabolism v2.232	GATC	Sarah Leigh Phenotypes for gene: GATC were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 42, OMIM:618839
17 Mar 2022	Likely inborn error of metabolism v2.231	GATC	Sarah Leigh Mode of inheritance for gene: GATC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
17 Mar 2022	Congenital myopathy v2.83	UNC45B	Sarah Leigh commented on gene: UNC45B: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.
17 Mar 2022	Congenital myopathy v2.83	UNC45B	Sarah Leigh Deleted their comment
17 Mar 2022	Congenital myopathy v2.83	UNC45B	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: UNC45B.
17 Mar 2022	Congenital myopathy v2.83	UNC45B	Sarah Leigh Classified gene: UNC45B as Amber List (moderate evidence)
17 Mar 2022	Congenital myopathy v2.83	UNC45B	Sarah Leigh Gene: unc45b has been classified as Amber List (Moderate Evidence).
17 Mar 2022	Congenital myopathy v2.82	KY	Sarah Leigh Deleted their comment
17 Mar 2022	Congenital myopathy v2.82	KY	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: KY.
17 Mar 2022	Congenital myopathy v2.82	KY	Sarah Leigh Classified gene: KY as Amber List (moderate evidence)
17 Mar 2022	Congenital myopathy v2.82	KY	Sarah Leigh Added comment: Comment on list classification: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.
17 Mar 2022	Congenital myopathy v2.82	KY	Sarah Leigh Gene: ky has been classified as Amber List (Moderate Evidence).
17 Mar 2022	Congenital myopathy v2.81	KY	Sarah Leigh Deleted their comment
17 Mar 2022	Congenital myopathy v2.81	GFER	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: GFER.
17 Mar 2022	Congenital myopathy v2.81	GFER	Sarah Leigh Classified gene: GFER as Amber List (moderate evidence)
17 Mar 2022	Congenital myopathy v2.81	GFER	Sarah Leigh Gene: gfer has been classified as Amber List (Moderate Evidence).
17 Mar 2022	Congenital myopathy v2.80	GFER	Sarah Leigh reviewed gene: GFER: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
17 Mar 2022	Congenital myopathy v2.80	GFER	Sarah Leigh Deleted their review
17 Mar 2022	Intellectual disability v3.1520	GLS	Arina Puzriakova Tag for-review was removed from gene: GLS. Tag watchlist tag was added to gene: GLS.
17 Mar 2022	Undiagnosed metabolic disorders v1.514	GLS	Arina Puzriakova Tag watchlist tag was added to gene: GLS.
17 Mar 2022	Undiagnosed metabolic disorders v1.514	GLS	Arina Puzriakova Tag for-review was removed from gene: GLS.
16 Mar 2022	Renal ciliopathies v1.61	DLG5	Eleanor Williams commented on gene: DLG5: Changed the mode of inheritance to be inline with that recommended by the NHS reviewer. Removed the Q3_21_MOI and Q3_21_NHS_review tags.
16 Mar 2022	Renal ciliopathies v1.61	DLG5	Eleanor Williams Tag Q3_21_MOI was removed from gene: DLG5. Tag Q3_21_NHS_review was removed from gene: DLG5.
16 Mar 2022	Renal ciliopathies v1.61	DLG5	Eleanor Williams Mode of inheritance for gene: DLG5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.149	ABCB7	Eleanor Williams Added comment: Comment on mode of inheritance: Changed the mode of inheritance now this gene has been demoted to amber on this panel and removed the Q3_21_MOI tag.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.149	ABCB7	Eleanor Williams Mode of inheritance for gene: ABCB7 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
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ABCB7	Eleanor Williams Tag Q3_21_MOI was removed from gene: ABCB7.
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	GLS	Eleanor Williams commented on gene: GLS
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	GLS	Eleanor Williams Tag for-review was removed from gene: GLS. Tag watchlist tag was added to gene: GLS.
16 Mar 2022	Multiple monogenic benign skin tumours v1.20	NOTCH3	Eleanor Williams commented on gene: NOTCH3: Removed the Q4_21_expert_review and Q4_21_NHS_review tags from this gene, and added the watchlist tag as it has only enough evidence for Amber at the moment. If more evidence is found to support the gene-disease association then the eligibility criteria for the panel needs to be expanded before promoting the gene to green.
16 Mar 2022	Multiple monogenic benign skin tumours v1.20	NOTCH3	Eleanor Williams Tag Q4_21_expert_review was removed from gene: NOTCH3. Tag Q4_21_NHS_review was removed from gene: NOTCH3. Tag watchlist tag was added to gene: NOTCH3.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	FAR1	Arina Puzriakova changed review comment from: Comment on mode of inheritance: As only 2/4 families with biallelic variants in this gene presented with epilepsy, in 2019, the rating was set to Amber for this allelic requirement (no new related evidence since). However, there is now evidence supporting pathogenicity of monoallelic variants affecting the Arg480 residue, and the number of unrelated individuals with seizures (8) reaches the threshold for inclusion with the monoallelic MOI. FAR1 will be flagged for GMS expert review to determine the most appropriate MOI and rating on this panel (note that if MOI is set to 'Monoallelic' only, patients with biallelic variants would still be picked up by the Genomics England pipeline); to: Comment on mode of inheritance: As only 2/4 families with biallelic variants in this gene presented with epilepsy, in 2019, the rating was set to Amber for this allelic requirement (no new related evidence since). However, there is now evidence supporting pathogenicity of monoallelic variants affecting the Arg480 residue, and the number of unrelated individuals with seizures (8) reaches the threshold for inclusion with the monoallelic MOI. FAR1 will be flagged for GMS expert review to determine the most appropriate MOI and rating on this panel.
16 Mar 2022	Fetal anomalies v1.844	TUBA8	Arina Puzriakova Classified gene: TUBA8 as Amber List (moderate evidence)
16 Mar 2022	Fetal anomalies v1.844	TUBA8	Arina Puzriakova Gene: tuba8 has been classified as Amber List (Moderate Evidence).
16 Mar 2022	Fetal anomalies v1.843	TUBA8	Arina Puzriakova Tag for-review was removed from gene: TUBA8.
16 Mar 2022	Fetal anomalies v1.843	TUBA8	Arina Puzriakova commented on gene: TUBA8
16 Mar 2022	Fetal anomalies v1.843	NEK9	Arina Puzriakova Classified gene: NEK9 as Green List (high evidence)
16 Mar 2022	Fetal anomalies v1.843	NEK9	Arina Puzriakova Gene: nek9 has been classified as Green List (High Evidence).
16 Mar 2022	Fetal anomalies v1.842	NEK9	Arina Puzriakova Tag for-review was removed from gene: NEK9.
16 Mar 2022	Fetal anomalies v1.842	NEK9	Arina Puzriakova commented on gene: NEK9: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37441-Loss	Eleanor Williams commented on Region: ISCA-37441-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37423-Gain	Arina Puzriakova commented on Region: ISCA-37423-Gain
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37423-Gain	Arina Puzriakova commented on Region: ISCA-37423-Gain
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37423-Gain	Arina Puzriakova commented on Region: ISCA-37423-Gain
16 Mar 2022	Clefting v2.66	ISCA-37423-Gain	Arina Puzriakova commented on Region: ISCA-37423-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37423-Loss	Arina Puzriakova commented on Region: ISCA-37423-Loss
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37423-Loss	Arina Puzriakova commented on Region: ISCA-37423-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37441-Loss	Eleanor Williams commented on Region: ISCA-37441-Loss
16 Mar 2022	Rare syndromic craniosynostosis or isolated multisuture synostosis v2.67	ISCA-37441-Loss	Eleanor Williams commented on Region: ISCA-37441-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
16 Mar 2022	Undiagnosed metabolic disorders v1.514	ISCA-37440-Loss	Eleanor Williams commented on Region: ISCA-37440-Loss
16 Mar 2022	Malformations of cortical development v2.137	ISCA-37430-Loss	Arina Puzriakova commented on Region: ISCA-37430-Loss
16 Mar 2022	Mitochondrial disorders v2.93	ISCA-37440-Loss	Eleanor Williams commented on Region: ISCA-37440-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37430-Gain	Arina Puzriakova commented on Region: ISCA-37430-Gain
16 Mar 2022	Hereditary neuropathy v1.442	ISCA-37436-Gain	Arina Puzriakova commented on Region: ISCA-37436-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37434-Loss	Arina Puzriakova commented on Region: ISCA-37434-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37434-Loss	Arina Puzriakova commented on Region: ISCA-37434-Loss
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37434-Loss	Arina Puzriakova commented on Region: ISCA-37434-Loss
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37434-Loss	Arina Puzriakova commented on Region: ISCA-37434-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37440-Loss	Eleanor Williams commented on Region: ISCA-37440-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37430-Loss	Arina Puzriakova commented on Region: ISCA-37430-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37430-Loss	Arina Puzriakova commented on Region: ISCA-37430-Loss
16 Mar 2022	Likely inborn error of metabolism v2.230	ISCA-37440-Loss	Eleanor Williams commented on Region: ISCA-37440-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37429-Loss	Arina Puzriakova commented on Region: ISCA-37429-Loss
16 Mar 2022	Hereditary neuropathy v1.442	ISCA-37436-Loss	Eleanor Williams commented on Region: ISCA-37436-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37429-Loss	Arina Puzriakova commented on Region: ISCA-37429-Loss
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37429-Loss	Arina Puzriakova commented on Region: ISCA-37429-Loss
16 Mar 2022	Congenital myopathy v2.80	ISCA-37429-Loss	Arina Puzriakova commented on Region: ISCA-37429-Loss
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37429-Loss	Arina Puzriakova commented on Region: ISCA-37429-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-46299-Gain	Arina Puzriakova commented on Region: ISCA-46299-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37501-Loss	Arina Puzriakova commented on Region: ISCA-37501-Loss
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37501-Loss	Arina Puzriakova commented on Region: ISCA-37501-Loss
16 Mar 2022	Severe microcephaly v2.294	ISCA-37501-Loss	Arina Puzriakova commented on Region: ISCA-37501-Loss
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37501-Loss	Arina Puzriakova commented on Region: ISCA-37501-Loss
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37501-Loss	Arina Puzriakova commented on Region: ISCA-37501-Loss
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37478-Loss	Eleanor Williams commented on Region: ISCA-37478-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37494-Gain	Arina Puzriakova commented on Region: ISCA-37494-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37493-Loss	Arina Puzriakova commented on Region: ISCA-37493-Loss
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37493-Loss	Arina Puzriakova commented on Region: ISCA-37493-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37494-Loss	Arina Puzriakova commented on Region: ISCA-37494-Loss
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37478-Gain	Eleanor Williams commented on Region: ISCA-37478-Gain
16 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.167	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
16 Mar 2022	Paroxysmal central nervous system disorders v1.41	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss
16 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.537	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
16 Mar 2022	Brain channelopathy v1.78	ISCA-37468-Loss	Arina Puzriakova commented on Region: ISCA-37468-Loss
16 Mar 2022	Clefting v2.66	ISCA-37467-Gain	Arina Puzriakova commented on Region: ISCA-37467-Gain
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss
16 Mar 2022	COVID-19 research v1.116	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss
16 Mar 2022	Neonatal diabetes v2.38	ISCA-37442-Gain	Arina Puzriakova commented on Region: ISCA-37442-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss
16 Mar 2022	Clefting v2.66	ISCA-37446-Loss	Eleanor Williams commented on Region: ISCA-37446-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37433-Gain	Arina Puzriakova commented on Region: ISCA-37433-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37446-Gain	Arina Puzriakova commented on Region: ISCA-37446-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37443-Loss	Arina Puzriakova commented on Region: ISCA-37443-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37439-Gain	Arina Puzriakova commented on Region: ISCA-37439-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	Clefting v2.66	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.537	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	COVID-19 research v1.116	ISCA-37433-Loss	Arina Puzriakova commented on Region: ISCA-37433-Loss
16 Mar 2022	Renal ciliopathies v1.60	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Rare multisystem ciliopathy disorders v1.159	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	CAKUT v1.167	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Monogenic diabetes v2.47	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Cystic kidney disease v2.36	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Familial diabetes v1.66	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.66	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Neonatal cholestasis v1.24	ISCA-37432-Loss	Arina Puzriakova commented on Region: ISCA-37432-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37432-Gain	Arina Puzriakova commented on Region: ISCA-37432-Gain
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37432-Gain	Arina Puzriakova commented on Region: ISCA-37432-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37431-Gain	Arina Puzriakova commented on Region: ISCA-37431-Gain
16 Mar 2022	Paediatric or syndromic cardiomyopathy v1.68	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	RASopathies v1.78	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	Pigmentary skin disorders v1.46	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	Neurofibromatosis Type 1 v1.27	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	Familial Tumours Syndromes of the central & peripheral Nervous system v1.12	ISCA-37431-Loss	Arina Puzriakova commented on Region: ISCA-37431-Loss
16 Mar 2022	Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.116	ISCA-37425-Loss	Arina Puzriakova commented on Region: ISCA-37425-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37425-Loss	Arina Puzriakova commented on Region: ISCA-37425-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37425-Gain	Arina Puzriakova commented on Region: ISCA-37425-Gain
16 Mar 2022	Severe microcephaly v2.294	ISCA-37425-Gain	Arina Puzriakova commented on Region: ISCA-37425-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37424-Loss	Arina Puzriakova commented on Region: ISCA-37424-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37421-Gain	Arina Puzriakova commented on Region: ISCA-37421-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37421-Loss	Arina Puzriakova commented on Region: ISCA-37421-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37420-Loss	Arina Puzriakova commented on Region: ISCA-37420-Loss
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37420-Loss	Arina Puzriakova commented on Region: ISCA-37420-Loss
16 Mar 2022	Rare syndromic craniosynostosis or isolated multisuture synostosis v2.67	ISCA-37420-Loss	Arina Puzriakova commented on Region: ISCA-37420-Loss
16 Mar 2022	Congenital myopathy v2.80	ISCA-37420-Loss	Arina Puzriakova commented on Region: ISCA-37420-Loss
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37420-Loss	Arina Puzriakova commented on Region: ISCA-37420-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37418-Gain	Arina Puzriakova commented on Region: ISCA-37418-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37418-Loss	Arina Puzriakova commented on Region: ISCA-37418-Loss
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37418-Loss	Arina Puzriakova commented on Region: ISCA-37418-Loss
16 Mar 2022	Ichthyosis and erythrokeratoderma v1.72	ISCA-37417-Loss	Arina Puzriakova commented on Region: ISCA-37417-Loss
16 Mar 2022	Autosomal recessive congenital ichthyosis v1.14	ISCA-37417-Loss	Arina Puzriakova commented on Region: ISCA-37417-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37415-Loss	Arina Puzriakova commented on Region: ISCA-37415-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37415-Loss	Arina Puzriakova commented on Region: ISCA-37415-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37415-Gain	Arina Puzriakova commented on Region: ISCA-37415-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37411-Loss	Arina Puzriakova commented on Region: ISCA-37411-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37411-Loss	Arina Puzriakova commented on Region: ISCA-37411-Loss
16 Mar 2022	Renal ciliopathies v1.60	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Rare multisystem ciliopathy disorders v1.159	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Cystic kidney disease v2.36	ISCA-37405-Loss	Arina Puzriakova commented on Region: ISCA-37405-Loss
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Congenital hypothyroidism v2.10	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37404-Loss	Arina Puzriakova commented on Region: ISCA-37404-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37404-Gain	Arina Puzriakova commented on Region: ISCA-37404-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37400-Loss	Arina Puzriakova commented on Region: ISCA-37400-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37400-Gain	Arina Puzriakova commented on Region: ISCA-37400-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37397-Loss	Arina Puzriakova commented on Region: ISCA-37397-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37397-Gain	Arina Puzriakova commented on Region: ISCA-37397-Gain
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37397-Loss	Arina Puzriakova commented on Region: ISCA-37397-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37408-Loss	Ivone Leong commented on Region: ISCA-37408-Loss
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37408-Loss	Ivone Leong commented on Region: ISCA-37408-Loss
16 Mar 2022	Severe microcephaly v2.294	ISCA-37408-Loss	Ivone Leong commented on Region: ISCA-37408-Loss
16 Mar 2022	Congenital myopathy v2.80	ISCA-37408-Loss	Ivone Leong commented on Region: ISCA-37408-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37406-Loss	Ivone Leong commented on Region: ISCA-37406-Loss
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37406-Loss	Ivone Leong commented on Region: ISCA-37406-Loss
16 Mar 2022	Severe microcephaly v2.294	ISCA-37406-Loss	Ivone Leong commented on Region: ISCA-37406-Loss
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37406-Loss	Ivone Leong commented on Region: ISCA-37406-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Differences in sex development v2.59	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Sporadic aniridia v2.15	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Childhood solid tumours v2.27	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Adult solid tumours for rare disease v1.27	ISCA-37401-Loss	Ivone Leong commented on Region: ISCA-37401-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37396-Loss	Ivone Leong commented on Region: ISCA-37396-Loss
16 Mar 2022	Ocular coloboma v1.45	ISCA-37396-Loss	Ivone Leong commented on Region: ISCA-37396-Loss
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37396-Loss	Ivone Leong commented on Region: ISCA-37396-Loss
16 Mar 2022	Structural eye disease v1.117	ISCA-37396-Loss	Ivone Leong commented on Region: ISCA-37396-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-46295-Loss	Ivone Leong commented on Region: ISCA-46295-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-46295-Loss	Ivone Leong commented on Region: ISCA-46295-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-46290-Gain	Ivone Leong commented on Region: ISCA-46290-Gain
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-46290-Gain	Ivone Leong commented on Region: ISCA-46290-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37500-Loss	Ivone Leong commented on Region: ISCA-37500-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37486-Loss	Ivone Leong commented on Region: ISCA-37486-Loss
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37486-Loss	Ivone Leong commented on Region: ISCA-37486-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Congenital hypothyroidism v2.10	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss: The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37478-Loss	Ivone Leong commented on Region: ISCA-37478-Loss
16 Mar 2022	Limb disorders v2.75	ISCA-37394-Loss	Ivone Leong commented on Region: ISCA-37394-Loss
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37394-Loss	Ivone Leong commented on Region: ISCA-37394-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37394-Loss	Ivone Leong commented on Region: ISCA-37394-Loss
16 Mar 2022	Clefting v2.66	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Ocular coloboma v1.45	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Structural eye disease v1.117	ISCA-37393-Gain	Ivone Leong commented on Region: ISCA-37393-Gain
16 Mar 2022	Intellectual disability v3.1520	ISCA-37390-Loss	Ivone Leong commented on Region: ISCA-37390-Loss
16 Mar 2022	Severe microcephaly v2.294	ISCA-37390-Loss	Ivone Leong commented on Region: ISCA-37390-Loss
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37392-Loss	Arina Puzriakova commented on Region: ISCA-37392-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37392-Loss	Arina Puzriakova commented on Region: ISCA-37392-Loss
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37392-Loss	Arina Puzriakova commented on Region: ISCA-37392-Loss
16 Mar 2022	Intellectual disability v3.1520	ISCA-37392-Gain	Arina Puzriakova commented on Region: ISCA-37392-Gain
16 Mar 2022	Limb disorders v2.75	ISCA-37394-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37394-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37494-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37494-Loss was changed from None to . Required Overlap Percentage for ISCA-37494-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37494-Gain	Arina Puzriakova Haploinsufficiency Score for ISCA-37494-Gain was changed from None to . Required Overlap Percentage for ISCA-37494-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37439-Gain	Arina Puzriakova GRCh38 position for ISCA-37439-Gain was changed from 154336276-154660745 to 154396223-154555683. Required Overlap Percentage for ISCA-37439-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37468-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-46290-Gain	Arina Puzriakova GRCh38 position for ISCA-46290-Gain was changed from 48447780-52444265 to 48447780-52444264. Required Overlap Percentage for ISCA-46290-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-46299-Gain	Arina Puzriakova Haploinsufficiency Score for ISCA-46299-Gain was changed from None to . Required Overlap Percentage for ISCA-46299-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37423-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37423-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37423-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37392-Loss	Arina Puzriakova GRCh38 position for ISCA-37392-Loss was changed from 73330451-74728175 to 73330452-74728172. Required Overlap Percentage for ISCA-37392-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37392-Gain	Arina Puzriakova GRCh38 position for ISCA-37392-Gain was changed from 73330451-74728175 to 73330452-74728172. Required Overlap Percentage for ISCA-37392-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37425-Loss	Arina Puzriakova GRCh38 position for ISCA-37425-Loss was changed from 176301975-177586960 to 176301976-177620792. Required Overlap Percentage for ISCA-37425-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37425-Gain	Arina Puzriakova GRCh38 position for ISCA-37425-Gain was changed from 176301975-177586960 to 176301976-177620792. Required Overlap Percentage for ISCA-37425-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37390-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37390-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37429-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37429-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37443-Loss	Arina Puzriakova GRCh38 position for ISCA-37443-Loss was changed from 196029183-197617794 to 196029183-197617791. Required Overlap Percentage for ISCA-37443-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37394-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37394-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37440-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37440-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37408-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37408-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37397-Loss	Arina Puzriakova GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-23306924. Required Overlap Percentage for ISCA-37397-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37397-Gain	Arina Puzriakova GRCh38 position for ISCA-37397-Gain was changed from 21443089-23306926 to 21562828-23306924. Required Overlap Percentage for ISCA-37397-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37446-Gain	Arina Puzriakova GRCh38 position for ISCA-37446-Gain was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37433-Gain	Arina Puzriakova GRCh38 position for ISCA-37433-Gain was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37493-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37493-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37421-Loss	Arina Puzriakova GRCh38 position for ISCA-37421-Loss was changed from 147105904-147922392 to 147105904-147917509. Required Overlap Percentage for ISCA-37421-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37421-Gain	Arina Puzriakova GRCh38 position for ISCA-37421-Gain was changed from 147105904-147922392 to 147105904-147917509. Required Overlap Percentage for ISCA-37421-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37434-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37434-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37501-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to . Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37420-Loss	Arina Puzriakova GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37432-Gain	Arina Puzriakova GRCh38 position for ISCA-37432-Gain was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37431-Gain	Arina Puzriakova GRCh38 position for ISCA-37431-Gain was changed from 30835804-31891648 to 30780079-31937008. Triplosensitivity Score for ISCA-37431-Gain was changed from 3 to 2. Required Overlap Percentage for ISCA-37431-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37430-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37430-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37430-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37430-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37418-Loss	Arina Puzriakova GRCh38 position for ISCA-37418-Loss was changed from 16853797-20316338 to 16906714-20309889. Required Overlap Percentage for ISCA-37418-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37418-Gain	Arina Puzriakova GRCh38 position for ISCA-37418-Gain was changed from 16853797-20316338 to 16906714-20309889. Required Overlap Percentage for ISCA-37418-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37406-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37406-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37415-Loss	Arina Puzriakova GRCh38 position for ISCA-37415-Loss was changed from 15410597-16198411 to 15417854-16198408. Required Overlap Percentage for ISCA-37415-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37415-Gain	Arina Puzriakova GRCh38 position for ISCA-37415-Gain was changed from 15410597-16198411 to 15417854-16198408. Required Overlap Percentage for ISCA-37415-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37400-Loss	Arina Puzriakova GRCh38 position for ISCA-37400-Loss was changed from 29638675-30188534 to 29638676-30188531. Required Overlap Percentage for ISCA-37400-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37400-Gain	Arina Puzriakova GRCh38 position for ISCA-37400-Gain was changed from 29638675-30188534 to 29638676-30188531. Required Overlap Percentage for ISCA-37400-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37486-Loss	Arina Puzriakova GRCh38 position for ISCA-37486-Loss was changed from 28811313-29035181 to 28811314-29035178. Required Overlap Percentage for ISCA-37486-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37500-Loss	Arina Puzriakova GRCh38 position for ISCA-37500-Loss was changed from 82534141-84045981 to 82534140-84045981. Required Overlap Percentage for ISCA-37500-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37396-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37396-Loss was changed from None to . Required Overlap Percentage for ISCA-37396-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-46295-Loss	Arina Puzriakova GRCh38 position for ISCA-46295-Loss was changed from 31727418-32153205 to 31727418-32153204. Required Overlap Percentage for ISCA-46295-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37411-Loss	Arina Puzriakova GRCh38 position for ISCA-37411-Loss was changed from 30844901-32153207 to 30900686-32153204. Required Overlap Percentage for ISCA-37411-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37404-Gain	Arina Puzriakova GRCh38 position for ISCA-37404-Gain was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Gain was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37441-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37441-Loss was changed from 80 to 60.
16 Mar 2022	Intellectual disability v3.1520	ISCA-37424-Loss	Arina Puzriakova GRCh38 position for ISCA-37424-Loss was changed from 79923892-86983483 to 79923087-86979631. Required Overlap Percentage for ISCA-37424-Loss was changed from 80 to 60.
16 Mar 2022	Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.116	ISCA-37425-Loss	Arina Puzriakova GRCh38 position for ISCA-37425-Loss was changed from 176301975-177586960 to 176301976-177620792. Triplosensitivity Score for ISCA-37425-Loss was changed from to None. Required Overlap Percentage for ISCA-37425-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained young onset end-stage renal disease v1.33	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Unexplained kidney failure in young people v1.105	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Undiagnosed metabolic disorders v1.514	ISCA-37440-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37440-Loss was changed from 80 to 60.
16 Mar 2022	Extreme early-onset hypertension v1.14	TTC21B	John Sayer edited their review of gene: TTC21B: Added comment: Careful literature review supports the notion that biallelic, often hypomorph, missense variants in TTC21B are commonly associated with early-onset hypertension and histological features of both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension might shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.; Changed publications to: 24876116, 26940125, 34957165, 34805047, PMID: 35289079
16 Mar 2022	Childhood solid tumours v2.26	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Structural eye disease v1.116	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Structural eye disease v1.116	ISCA-37396-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37396-Loss was changed from None to . Required Overlap Percentage for ISCA-37396-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37394-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37394-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37434-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37434-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37501-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to . Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37418-Loss	Arina Puzriakova GRCh38 position for ISCA-37418-Loss was changed from 16853797-20316338 to 16906714-20309889. Required Overlap Percentage for ISCA-37418-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37406-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37406-Loss was changed from 80 to 60.
16 Mar 2022	Skeletal dysplasia v2.190	ISCA-37441-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37441-Loss was changed from 80 to 60.
16 Mar 2022	Severe microcephaly v2.294	ISCA-37425-Gain	Arina Puzriakova GRCh38 position for ISCA-37425-Gain was changed from 176301975-177586960 to 176301976-177620792. Haploinsufficiency Score for ISCA-37425-Gain was changed from None to . Required Overlap Percentage for ISCA-37425-Gain was changed from 80 to 60.
16 Mar 2022	Severe microcephaly v2.294	ISCA-37390-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37390-Loss was changed from None to . Required Overlap Percentage for ISCA-37390-Loss was changed from 80 to 60.
16 Mar 2022	Severe microcephaly v2.294	ISCA-37408-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37408-Loss was changed from None to . Required Overlap Percentage for ISCA-37408-Loss was changed from 80 to 60.
16 Mar 2022	Severe microcephaly v2.294	ISCA-37501-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to . Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
16 Mar 2022	Severe microcephaly v2.294	ISCA-37406-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37406-Loss was changed from None to . Required Overlap Percentage for ISCA-37406-Loss was changed from 80 to 60.
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37486-Loss	Arina Puzriakova GRCh38 position for ISCA-37486-Loss was changed from 28811313-29035181 to 28811314-29035178. Triplosensitivity Score for ISCA-37486-Loss was changed from None to . Required Overlap Percentage for ISCA-37486-Loss was changed from 80 to 60.
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Triplosensitivity Score for ISCA-37478-Loss was changed from None to . Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Severe early-onset obesity v2.49	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Triplosensitivity Score for ISCA-37404-Loss was changed from None to . Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Renal ciliopathies v1.60	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Renal ciliopathies v1.60	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	RASopathies v1.78	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	Rare multisystem ciliopathy disorders v1.159	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Rare multisystem ciliopathy disorders v1.159	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.537	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	Primary immunodeficiency or monogenic inflammatory bowel disease v2.537	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Pigmentary skin disorders v1.46	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Triplosensitivity Score for ISCA-37431-Loss was changed from None to . Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	Paroxysmal central nervous system disorders v1.41	ISCA-37468-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37429-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37429-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37408-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37408-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37420-Loss	Arina Puzriakova GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric motor neuronopathies v1.77	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Ocular coloboma v1.45	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Ocular coloboma v1.45	ISCA-37396-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37396-Loss was changed from None to . Required Overlap Percentage for ISCA-37396-Loss was changed from 80 to 60.
16 Mar 2022	Neurofibromatosis Type 1 v1.27	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37468-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37468-Loss was changed from None to . Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Adult onset neurodegenerative disorder v2.268	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Neonatal cholestasis v1.24	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Monogenic diabetes v2.47	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Mitochondrial disorders v2.93	ISCA-37440-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37440-Loss was changed from 80 to 60.
16 Mar 2022	Likely inborn error of metabolism v2.230	ISCA-37440-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37440-Loss was changed from 80 to 60.
16 Mar 2022	Malformations of cortical development v2.137	ISCA-37430-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37430-Loss was changed from 80 to 60.
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37392-Loss	Arina Puzriakova GRCh38 position for ISCA-37392-Loss was changed from 73330451-74728175 to 73330452-74728172. Required Overlap Percentage for ISCA-37392-Loss was changed from 80 to 60.
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37429-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37429-Loss was changed from 80 to 60.
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37397-Loss	Arina Puzriakova GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-23306924. Required Overlap Percentage for ISCA-37397-Loss was changed from 80 to 60.
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37420-Loss	Arina Puzriakova GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
16 Mar 2022	IUGR and IGF abnormalities v1.51	ISCA-37406-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37406-Loss was changed from 80 to 60.
16 Mar 2022	Ichthyosis and erythrokeratoderma v1.72	ISCA-37417-Loss	Arina Puzriakova GRCh38 position for ISCA-37417-Loss was changed from 6537771-8156914 to 6537771-8156913. Required Overlap Percentage for ISCA-37417-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary neuropathy v1.442	ISCA-37436-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37436-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary neuropathy v1.442	ISCA-37436-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37436-Gain was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia v1.299	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37468-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37468-Loss was changed from None to . Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Triplosensitivity Score for ISCA-37478-Loss was changed from None to . Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Hereditary ataxia with onset in adulthood v2.148	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-46290-Gain	Arina Puzriakova GRCh38 position for ISCA-46290-Gain was changed from 48447780-52444265 to 48447780-52444264. Haploinsufficiency Score for ISCA-46290-Gain was changed from None to . Required Overlap Percentage for ISCA-46290-Gain was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37423-Gain	Arina Puzriakova Haploinsufficiency Score for ISCA-37423-Gain was changed from None to . Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37429-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37429-Loss was changed from None to . Required Overlap Percentage for ISCA-37429-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37493-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37493-Loss was changed from None to . Required Overlap Percentage for ISCA-37493-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37434-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37434-Loss was changed from None to . Required Overlap Percentage for ISCA-37434-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37432-Gain	Arina Puzriakova GRCh38 position for ISCA-37432-Gain was changed from 36458167-37854617 to 36458167-37854616. Haploinsufficiency Score for ISCA-37432-Gain was changed from None to . Required Overlap Percentage for ISCA-37432-Gain was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37430-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37430-Loss was changed from None to . Required Overlap Percentage for ISCA-37430-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37415-Loss	Arina Puzriakova GRCh38 position for ISCA-37415-Loss was changed from 15410597-16198411 to 15417854-16198408. Triplosensitivity Score for ISCA-37415-Loss was changed from None to . Required Overlap Percentage for ISCA-37415-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-46295-Loss	Arina Puzriakova GRCh38 position for ISCA-46295-Loss was changed from 31727418-32153205 to 31727418-32153204. Triplosensitivity Score for ISCA-46295-Loss was changed from None to . Required Overlap Percentage for ISCA-46295-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37411-Loss	Arina Puzriakova GRCh38 position for ISCA-37411-Loss was changed from 30844901-32153207 to 30900686-32153204. Triplosensitivity Score for ISCA-37411-Loss was changed from None to . Required Overlap Percentage for ISCA-37411-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Triplosensitivity Score for ISCA-37478-Loss was changed from None to . Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Haploinsufficiency Score for ISCA-37478-Gain was changed from None to . Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Early onset or syndromic epilepsy v2.500	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Triplosensitivity Score for ISCA-37404-Loss was changed from None to . Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Familial Tumours Syndromes of the central & peripheral Nervous system v1.12	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37423-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37423-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37423-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37392-Loss	Arina Puzriakova GRCh38 position for ISCA-37392-Loss was changed from 73330451-74728175 to 73330452-74728172. Required Overlap Percentage for ISCA-37392-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37434-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37434-Loss was changed from 80 to 60.
16 Mar 2022	Familial non syndromic congenital heart disease v1.74	ISCA-37501-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to . Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
16 Mar 2022	Familial diabetes v1.66	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Differences in sex development v2.59	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.66	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Neonatal diabetes v2.38	ISCA-37442-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37442-Gain was changed from 80 to 60.
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37501-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37501-Loss was changed from None to . Required Overlap Percentage for ISCA-37501-Loss was changed from 80 to 60.
16 Mar 2022	Deafness and congenital structural abnormalities v1.19	ISCA-37396-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37396-Loss was changed from None to . Required Overlap Percentage for ISCA-37396-Loss was changed from 80 to 60.
16 Mar 2022	Cystic kidney disease v2.36	ISCA-37405-Loss	Arina Puzriakova GRCh38 position for ISCA-37405-Loss was changed from 110122329-110205017 to 110104531-110228181. Haploinsufficiency Score for ISCA-37405-Loss was changed from 3 to 30. Required Overlap Percentage for ISCA-37405-Loss was changed from 80 to 60.
16 Mar 2022	Cystic kidney disease v2.36	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Rare syndromic craniosynostosis or isolated multisuture synostosis v2.67	ISCA-37420-Loss	Arina Puzriakova GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
16 Mar 2022	Rare syndromic craniosynostosis or isolated multisuture synostosis v2.67	ISCA-37441-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37441-Loss was changed from 80 to 60.
16 Mar 2022	COVID-19 research v1.116	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	COVID-19 research v1.116	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Congenital myopathy v2.80	ISCA-37429-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37429-Loss was changed from 80 to 60.
16 Mar 2022	Congenital myopathy v2.80	ISCA-37408-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37408-Loss was changed from 80 to 60.
16 Mar 2022	Congenital myopathy v2.80	ISCA-37420-Loss	Arina Puzriakova GRCh38 position for ISCA-37420-Loss was changed from 45608879-46087510 to 45627800-46087514. Required Overlap Percentage for ISCA-37420-Loss was changed from 80 to 60.
16 Mar 2022	Congenital hypothyroidism v2.10	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Congenital hypothyroidism v2.10	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Clefting v2.66	ISCA-37423-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.
16 Mar 2022	Clefting v2.66	ISCA-37467-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37467-Gain was changed from 80 to 60.
16 Mar 2022	Clefting v2.66	ISCA-37393-Gain	Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
16 Mar 2022	Clefting v2.66	ISCA-37446-Loss	Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383. Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
16 Mar 2022	Clefting v2.66	ISCA-37433-Loss	Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
16 Mar 2022	Paediatric or syndromic cardiomyopathy v1.68	ISCA-37431-Loss	Arina Puzriakova GRCh38 position for ISCA-37431-Loss was changed from 30835804-31891648 to 30780079-31937008. Required Overlap Percentage for ISCA-37431-Loss was changed from 80 to 60.
16 Mar 2022	CAKUT v1.167	ISCA-37432-Loss	Arina Puzriakova GRCh38 position for ISCA-37432-Loss was changed from 36458167-37854617 to 36458167-37854616. Required Overlap Percentage for ISCA-37432-Loss was changed from 80 to 60.
16 Mar 2022	Brain channelopathy v1.78	ISCA-37468-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37468-Loss was changed from None to . Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
16 Mar 2022	Autosomal recessive congenital ichthyosis v1.14	ISCA-37417-Loss	Arina Puzriakova GRCh38 position for ISCA-37417-Loss was changed from 6537771-8156914 to 6537771-8156913. Required Overlap Percentage for ISCA-37417-Loss was changed from 80 to 60.
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37478-Loss	Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37478-Gain	Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728. Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
16 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.289	ISCA-37404-Loss	Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728. Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
16 Mar 2022	Sporadic aniridia v2.15	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Adult solid tumours for rare disease v1.27	ISCA-37401-Loss	Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
16 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.167	ISCA-37468-Loss	Arina Puzriakova Triplosensitivity Score for ISCA-37468-Loss was changed from None to . Required Overlap Percentage for ISCA-37468-Loss was changed from 80 to 60.
15 Mar 2022	Severe microcephaly v2.293	DPP6	Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: DPP6.
15 Mar 2022	Monogenic hearing loss v2.237	COL9A3	Eleanor Williams Tag for-review was removed from gene: COL9A3.
15 Mar 2022	Congenital myopathy v2.79	GFER	Sarah Leigh changed review comment from: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.; to: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
15 Mar 2022	Adult onset leukodystrophy v1.40	RNASET2	Sarah Leigh commented on gene: RNASET2
15 Mar 2022	Adult onset leukodystrophy v1.40	RNASET2	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: RNASET2.
15 Mar 2022	Adult onset leukodystrophy v1.40	POLR1C	Sarah Leigh commented on gene: POLR1C
15 Mar 2022	Adult onset leukodystrophy v1.40	POLR1C	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: POLR1C.
15 Mar 2022	Adult onset leukodystrophy v1.40	MARS	Sarah Leigh commented on gene: MARS
15 Mar 2022	Adult onset leukodystrophy v1.40	MARS	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: MARS.
15 Mar 2022	Adult onset leukodystrophy v1.40	COL4A2	Sarah Leigh commented on gene: COL4A2
15 Mar 2022	Adult onset leukodystrophy v1.40	COL4A2	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: COL4A2.
15 Mar 2022	Adult onset leukodystrophy v1.40	AARS	Sarah Leigh commented on gene: AARS
15 Mar 2022	Adult onset leukodystrophy v1.40	AARS	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AARS.
15 Mar 2022	Intellectual disability v3.1519	FAR1	Sarah Leigh reviewed gene: FAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439727, 30561787; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
15 Mar 2022	Intellectual disability v3.1519	FAR1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: FAR1.
15 Mar 2022	Hydrocephalus v2.127	MYMK	Sarah Leigh reviewed gene: MYMK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
15 Mar 2022	Hydrocephalus v2.127	MYMK	Sarah Leigh Deleted their review
15 Mar 2022	Hydrocephalus v2.127	MYMK	Sarah Leigh commented on gene: MYMK: As the recommendation is to demote MYMK from Green to Amber on this panel, the to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Hydrocephalus v2.127	MYMK	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: MYMK.
15 Mar 2022	Hydrocephalus v2.127	HYLS1	Sarah Leigh reviewed gene: HYLS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
15 Mar 2022	Hydrocephalus v2.127	HYLS1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: HYLS1.
15 Mar 2022	Hydrocephalus v2.127	ERF	Sarah Leigh reviewed gene: ERF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
15 Mar 2022	Hydrocephalus v2.127	ERF	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: ERF.
15 Mar 2022	Holoprosencephaly v2.27	DISP1	Sarah Leigh commented on gene: DISP1: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Holoprosencephaly v2.27	DISP1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: DISP1.
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	AFG3L2	Sarah Leigh commented on gene: AFG3L2: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	AFG3L2	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AFG3L2.
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	GBA	Sarah Leigh reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	GBA	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: GBA.
15 Mar 2022	Early onset or syndromic epilepsy v2.499	EEF1A2	Sarah Leigh Mode of pathogenicity for gene: EEF1A2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Hereditary spastic paraplegia v1.289	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Structural basal ganglia disorders v1.30	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Hereditary ataxia v1.298	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Brain channelopathy v1.77	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	HTT_CAG	Arina Puzriakova commented on STR: HTT_CAG
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Paroxysmal central nervous system disorders v1.40	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Hereditary ataxia v1.298	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Brain channelopathy v1.77	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	TBP_CAG	Arina Puzriakova commented on STR: TBP_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4B1	Sarah Leigh commented on gene: AP4B1
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4S1	Sarah Leigh commented on gene: AP4S1
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4E1	Sarah Leigh commented on gene: AP4E1
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4M1	Sarah Leigh commented on gene: AP4M1
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4E1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AP4E1.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4B1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AP4B1.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4S1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AP4S1.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AP4M1	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: AP4M1.
15 Mar 2022	Hereditary neuropathy or pain disorder v1.88	SLC12A6	Sarah Leigh commented on gene: SLC12A6: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Hereditary neuropathy or pain disorder v1.88	SPTBN4	Sarah Leigh commented on gene: SPTBN4
15 Mar 2022	Hereditary neuropathy or pain disorder v1.88	NEMF	Sarah Leigh commented on gene: NEMF
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Early onset or syndromic epilepsy v2.498	CPA6	Sarah Leigh commented on gene: CPA6: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Intellectual disability v3.1519	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Hereditary neuropathy v1.441	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Early onset or syndromic epilepsy v2.498	SCN8A	Sarah Leigh commented on gene: SCN8A: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Hereditary ataxia v1.298	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	PPP2R2B_CAG	Arina Puzriakova commented on STR: PPP2R2B_CAG
15 Mar 2022	Possible mitochondrial disorder - nuclear genes v1.69	HPDL	Sarah Leigh commented on gene: HPDL: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Mitochondrial disorders v2.92	HPDL	Sarah Leigh commented on gene: HPDL: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Rhabdomyolysis and metabolic muscle disorders v1.78	ISCU	Sarah Leigh commented on gene: ISCU: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Hereditary neuropathy v1.441	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG
15 Mar 2022	Hereditary ataxia v1.298	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	NOP56_GGCCTG	Arina Puzriakova commented on STR: NOP56_GGCCTG
15 Mar 2022	Early onset or syndromic epilepsy v2.498	SLC5A6	Sarah Leigh commented on gene: SLC5A6: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
15 Mar 2022	Rhabdomyolysis and metabolic muscle disorders v1.78	ISCU	Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: ISCU.
15 Mar 2022	Lysosomal storage disorder v1.78	ARSG	Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least five variants reported in at least four unrelated cases, together with supportive functional and animal models.; to: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least five variants reported in at least four unrelated cases, together with supportive functional studies and animal models.
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	JPH3_CTG	Sarah Leigh commented on STR: JPH3_CTG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	JPH3_CTG	Sarah Leigh commented on STR: JPH3_CTG
15 Mar 2022	Early onset dystonia v1.111	JPH3_CTG	Sarah Leigh commented on STR: JPH3_CTG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	JPH3_CTG	Sarah Leigh commented on STR: JPH3_CTG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	JPH3_CTG	Sarah Leigh commented on STR: JPH3_CTG
15 Mar 2022	Skeletal muscle channelopathy v1.39	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Mitochondrial disorders v2.92	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Intellectual disability v3.1519	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Hereditary neuropathy v1.441	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Paroxysmal central nervous system disorders v1.40	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Likely inborn error of metabolism v2.229	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Hereditary spastic paraplegia v1.289	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Hypertrophic cardiomyopathy v2.38	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Hereditary ataxia v1.298	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	FXN_GAA	Sarah Leigh commented on STR: FXN_GAA
15 Mar 2022	Skeletal Muscle Channelopathies v1.45	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Mitochondrial disorders v2.92	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Paediatric motor neuronopathies v1.76	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Intellectual disability v3.1519	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Gastrointestinal neuromuscular disorders v1.21	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Fetal hydrops v1.50	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Fetal anomalies v1.842	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Intellectual disability v3.1519	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Early onset or syndromic epilepsy v2.498	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Paroxysmal central nervous system disorders v1.40	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Hereditary ataxia v1.298	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
15 Mar 2022	Brain channelopathy v1.77	CSTB_CCCCGCCCCGCG	Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
15 Mar 2022	Likely inborn error of metabolism v2.229	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	DDG2P v2.65	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Congenital myopathy v2.79	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Congenital muscular dystrophy v2.27	DMPK_CTG	Eleanor Williams commented on STR: DMPK_CTG
15 Mar 2022	Skeletal muscle channelopathy v1.39	CNBP_CCTG	Eleanor Williams commented on STR: CNBP_CCTG
15 Mar 2022	Skeletal Muscle Channelopathies v1.45	CNBP_CCTG	Eleanor Williams commented on STR: CNBP_CCTG
15 Mar 2022	Fetal anomalies v1.842	CNBP_CCTG	Eleanor Williams commented on STR: CNBP_CCTG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	FMR1_CGG	Sarah Leigh commented on STR: FMR1_CGG
15 Mar 2022	Intellectual disability v3.1519	FMR1_CGG	Sarah Leigh commented on STR: FMR1_CGG
15 Mar 2022	Hereditary neuropathy v1.441	FMR1_CGG	Sarah Leigh commented on STR: FMR1_CGG
15 Mar 2022	Distal myopathies v1.45	CNBP_CCTG	Eleanor Williams commented on STR: CNBP_CCTG
15 Mar 2022	Hereditary ataxia v1.298	FMR1_CGG	Sarah Leigh commented on STR: FMR1_CGG
15 Mar 2022	Primary ovarian insufficiency v1.67	FMR1_CGG	Sarah Leigh commented on STR: FMR1_CGG
15 Mar 2022	Paroxysmal central nervous system disorders v1.40	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Hereditary ataxia v1.298	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Brain channelopathy v1.77	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	CACNA1A_CAG	Eleanor Williams commented on STR: CACNA1A_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Intellectual disability v3.1519	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	C9orf72_GGGGCC	Eleanor Williams commented on STR: C9orf72_GGGGCC
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Undiagnosed metabolic disorders v1.513	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Intellectual disability v3.1519	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Hereditary neuropathy v1.441	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Hereditary ataxia v1.298	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATXN7_CAG	Eleanor Williams commented on STR: ATXN7_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Intellectual disability v3.1519	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Hereditary neuropathy v1.441	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Hereditary ataxia v1.298	ATXN3	Eleanor Williams Deleted their review
15 Mar 2022	Hereditary ataxia v1.298	ATXN3	Eleanor Williams Deleted their comment
15 Mar 2022	Hereditary ataxia v1.298	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN3	Eleanor Williams Deleted their review
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN3	Eleanor Williams Deleted their comment
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN3	Eleanor Williams commented on gene: ATXN3
15 Mar 2022	Hereditary ataxia v1.298	ATXN3	Eleanor Williams commented on gene: ATXN3
15 Mar 2022	Early onset dystonia v1.111	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	ATXN3_CAG	Eleanor Williams commented on STR: ATXN3_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Intellectual disability v3.1519	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Hereditary neuropathy v1.441	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Hereditary ataxia v1.298	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Early onset dystonia v1.111	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	ATXN2_CAG	Ivone Leong commented on STR: ATXN2_CAG
15 Mar 2022	Thoracic dystrophies v1.18	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Skeletal dysplasia v2.189	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Intellectual disability v3.1519	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Hereditary spastic paraplegia v1.289	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Hereditary neuropathy v1.441	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Hereditary ataxia v1.298	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Early onset dystonia v1.111	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATXN10_ATTCT	Ivone Leong commented on STR: ATXN10_ATTCT
15 Mar 2022	Hereditary ataxia v1.298	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Intellectual disability v3.1519	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Hereditary spastic paraplegia v1.289	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Hereditary neuropathy v1.441	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATXN1_CAG	Ivone Leong commented on STR: ATXN1_CAG
15 Mar 2022	Paroxysmal central nervous system disorders v1.40	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Hereditary ataxia with onset in adulthood v2.147	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Hereditary ataxia v1.298	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Early onset or syndromic epilepsy v2.498	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Brain channelopathy v1.77	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	ATN1_CAG	Ivone Leong commented on STR: ATN1_CAG
15 Mar 2022	Adult onset neurodegenerative disorder v2.267	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Paediatric motor neuronopathies v1.76	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Hereditary neuropathy or pain disorder v1.88	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Hereditary neuropathy v1.441	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Distal myopathies v1.45	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Congenital myopathy v2.79	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	AR_CAG	Ivone Leong commented on STR: AR_CAG
15 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.77	LDB3	Ivone Leong Classified gene: LDB3 as Amber List (moderate evidence)
15 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.77	LDB3	Ivone Leong Added comment: Comment on list classification: Demoted from Green to Amber. This gene is associated with a phenotype in OMIM and Gene2Phenotype (requires clinical review). However, based on the expert reviews there is not enough evidence to support a gene-disease association. Therefore this gene has been given an Amber rating.
15 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.77	LDB3	Ivone Leong Gene: ldb3 has been classified as Amber List (Moderate Evidence).
15 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.76	LDB3	Ivone Leong Added comment: Comment on publications: Added new publications
15 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.76	LDB3	Ivone Leong Publications for gene: LDB3 were set to
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.16	PADI6	Catherine Snow Tag for-review was removed from gene: PADI6.
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.16	SUZ12	Catherine Snow Tag for-review was removed from gene: SUZ12.
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.16	SUZ12	Catherine Snow commented on gene: SUZ12
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.16	PADI6	Catherine Snow commented on gene: PADI6
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.15	SUZ12	Catherine Snow Source Expert Review Green was added to SUZ12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Segmental overgrowth disorders - Deep sequencing v2.15	PADI6	Catherine Snow Source Expert Review Green was added to PADI6. Rating Changed from Red List (low evidence) to Green List (high evidence)
14 Mar 2022	Pigmentary skin disorders v1.45	ANAPC1	Catherine Snow Tag for-review was removed from gene: ANAPC1.
14 Mar 2022	Pigmentary skin disorders v1.45	ANAPC1	Catherine Snow commented on gene: ANAPC1
14 Mar 2022	Pigmentary skin disorders v1.44	ANAPC1	Catherine Snow Source Expert Review Green was added to ANAPC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Palmoplantar keratodermas v1.12	ST14	Catherine Snow Tag for-review was removed from gene: ST14.
14 Mar 2022	Palmoplantar keratodermas v1.12	ST14	Catherine Snow commented on gene: ST14
14 Mar 2022	Palmoplantar keratodermas v1.11	ST14	Catherine Snow Source Expert Review Red was added to ST14. Rating Changed from Green List (high evidence) to Red List (low evidence)
14 Mar 2022	Cutaneous photosensitivity with a likely genetic cause v1.10	ANAPC1	Catherine Snow Tag for-review was removed from gene: ANAPC1. Tag Q4_21_NHS_review was removed from gene: ANAPC1.
14 Mar 2022	Cutaneous photosensitivity with a likely genetic cause v1.10	ANAPC1	Catherine Snow commented on gene: ANAPC1: Submitted on behalf of NHS GMS "Agree. There is an intronic variant which will be outside the targeted region of exomes which has been identified in multiple patients (c.2705-198C-T, NM_022662.3). This gene will also provide difficulties due to pseudogenes - coverage of uniquely mapping reads is ~50% (TWIST exome).""Green - mutations in ANAPC1 cause RTS type 1 (e.g. Ajeawung et al. AJHG 2019)"
14 Mar 2022	Cutaneous photosensitivity with a likely genetic cause v1.10	ANAPC1	Catherine Snow commented on gene: ANAPC1
14 Mar 2022	Cutaneous photosensitivity with a likely genetic cause v1.9	ANAPC1	Catherine Snow Source Expert Review Green was added to ANAPC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Ectodermal dysplasia v1.37	C3orf52	Catherine Snow Tag for-review was removed from gene: C3orf52.
14 Mar 2022	Ectodermal dysplasia v1.37	ANAPC1	Catherine Snow Tag for-review was removed from gene: ANAPC1. Tag Q4_21_NHS_review was removed from gene: ANAPC1.
14 Mar 2022	Ectodermal dysplasia v1.37	ST14	Catherine Snow Tag for-review was removed from gene: ST14.
14 Mar 2022	Ectodermal dysplasia v1.37	ST14	Catherine Snow changed review comment from: The rating of this gene has been updated following NHS Genomic Medicine Service approval.Submitted on behalf of NHS GMS "I think we can keep ST14 green for ED because there is skin and hair involvement and some cases may well come as a hair phenotype query"; to: The rating of this gene has been updated following NHS Genomic Medicine Service approval. Submitted on behalf of NHS GMS."I think we can keep ST14 green for ED because there is skin and hair involvement and some cases may well come as a hair phenotype query"
14 Mar 2022	Ectodermal dysplasia v1.37	PRKD1	Catherine Snow changed review comment from: The rating of this gene has been updated following NHS Genomic Medicine Service approval.Submitted on behalf of NHS GMS "Green - rare form of EB (telangietasia-ED-brachydactyly-cardia anomaly syndrome) (Alter et al. J Med Genet 2021)"; to: The rating of this gene has been updated following NHS Genomic Medicine Service approval.Submitted on behalf of NHS GMS. "Green - rare form of EB (telangietasia-ED-brachydactyly-cardia anomaly syndrome) (Alter et al. J Med Genet 2021)"
14 Mar 2022	Ectodermal dysplasia v1.37	PRKD1	Catherine Snow Tag for-review was removed from gene: PRKD1.
14 Mar 2022	Ectodermal dysplasia v1.37	C3orf52	Catherine Snow commented on gene: C3orf52
14 Mar 2022	Ectodermal dysplasia v1.37	ANAPC1	Catherine Snow commented on gene: ANAPC1
14 Mar 2022	Ectodermal dysplasia v1.37	ST14	Catherine Snow commented on gene: ST14
14 Mar 2022	Ectodermal dysplasia v1.37	PRKD1	Catherine Snow commented on gene: PRKD1
14 Mar 2022	Ectodermal dysplasia v1.36	C3orf52	Catherine Snow Source Expert Review Green was added to C3orf52. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Ectodermal dysplasia v1.36	ANAPC1	Catherine Snow Source Expert Review Green was added to ANAPC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Ectodermal dysplasia v1.36	ST14	Catherine Snow Source Expert Review Green was added to ST14. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Ectodermal dysplasia v1.36	PRKD1	Catherine Snow Source Expert Review Green was added to PRKD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CACNA1I	Ivone Leong Tag Q4_21_rating was removed from gene: CACNA1I.
14 Mar 2022	Intellectual disability v3.1519	ZNF699	Ivone Leong Tag Q4_21_rating was removed from gene: ZNF699.
14 Mar 2022	Intellectual disability v3.1519	YIPF5	Ivone Leong Tag Q2_21_rating was removed from gene: YIPF5.
14 Mar 2022	Intellectual disability v3.1519	WDR4	Ivone Leong Tag Q2_21_rating was removed from gene: WDR4.
14 Mar 2022	Intellectual disability v3.1519	VPS41	Ivone Leong Tag Q2_21_rating was removed from gene: VPS41.
14 Mar 2022	Intellectual disability v3.1519	VPS11	Ivone Leong Tag Q2_21_rating was removed from gene: VPS11.
14 Mar 2022	Intellectual disability v3.1519	UFSP2	Ivone Leong Tag Q2_21_rating was removed from gene: UFSP2. Tag Q2_21_expert_review was removed from gene: UFSP2.
14 Mar 2022	Intellectual disability v3.1519	UBE4A	Ivone Leong Tag Q2_21_rating was removed from gene: UBE4A.
14 Mar 2022	Intellectual disability v3.1519	TP73	Ivone Leong Tag Q3_21_rating was removed from gene: TP73.
14 Mar 2022	Intellectual disability v3.1519	TNPO2	Ivone Leong Tag Q3_21_rating was removed from gene: TNPO2.
14 Mar 2022	Intellectual disability v3.1519	TMEM222	Ivone Leong Tag Q2_21_rating was removed from gene: TMEM222.
14 Mar 2022	Intellectual disability v3.1519	TCF7L2	Ivone Leong Tag Q4_21_rating was removed from gene: TCF7L2.
14 Mar 2022	Intellectual disability v3.1519	SYNCRIP	Ivone Leong Tag Q3_21_rating was removed from gene: SYNCRIP.
14 Mar 2022	Intellectual disability v3.1519	SPTBN1	Ivone Leong Tag Q3_21_rating was removed from gene: SPTBN1.
14 Mar 2022	Intellectual disability v3.1519	SPEN	Ivone Leong Tag Q2_21_rating was removed from gene: SPEN.
14 Mar 2022	Intellectual disability v3.1519	SNIP1	Ivone Leong Tag Q4_21_expert_review was removed from gene: SNIP1.
14 Mar 2022	Intellectual disability v3.1519	SMARCA5	Ivone Leong Tag Q2_21_rating was removed from gene: SMARCA5. Tag Q2_21_NHS_review was removed from gene: SMARCA5.
14 Mar 2022	Intellectual disability v3.1519	SIN3B	Ivone Leong Tag Q2_21_rating was removed from gene: SIN3B.
14 Mar 2022	Intellectual disability v3.1519	SIAH1	Ivone Leong Tag Q2_21_rating was removed from gene: SIAH1.
14 Mar 2022	Intellectual disability v3.1519	SCYL1	Ivone Leong Tag Q2_21_rating was removed from gene: SCYL1.
14 Mar 2022	Intellectual disability v3.1519	SATB1	Ivone Leong Tag Q2_21_rating was removed from gene: SATB1.
14 Mar 2022	Intellectual disability v3.1519	RFX7	Ivone Leong Tag Q3_21_rating was removed from gene: RFX7.
14 Mar 2022	Intellectual disability v3.1519	RFX4	Ivone Leong Tag Q3_21_rating was removed from gene: RFX4.
14 Mar 2022	Intellectual disability v3.1519	RFX3	Ivone Leong Tag Q3_21_rating was removed from gene: RFX3.
14 Mar 2022	Intellectual disability v3.1519	PTPN4	Ivone Leong Tag Q3_21_rating was removed from gene: PTPN4.
14 Mar 2022	Intellectual disability v3.1519	PRICKLE2	Ivone Leong Tag Q4_21_rating was removed from gene: PRICKLE2.
14 Mar 2022	Intellectual disability v3.1519	PIGC	Ivone Leong Tag Q2_21_rating was removed from gene: PIGC.
14 Mar 2022	Intellectual disability v3.1519	PIDD1	Ivone Leong Tag Q3_21_rating was removed from gene: PIDD1.
14 Mar 2022	Intellectual disability v3.1519	PI4KA	Ivone Leong Tag Q3_21_rating was removed from gene: PI4KA.
14 Mar 2022	Intellectual disability v3.1519	PGM2L1	Ivone Leong Tag Q3_21_rating was removed from gene: PGM2L1.
14 Mar 2022	Intellectual disability v3.1519	PCDHGC4	Ivone Leong Tag Q3_21_rating was removed from gene: PCDHGC4.
14 Mar 2022	Intellectual disability v3.1519	OTUD5	Ivone Leong Tag Q2_21_rating was removed from gene: OTUD5.
14 Mar 2022	Intellectual disability v3.1519	NEUROD2	Ivone Leong Tag Q2_21_rating was removed from gene: NEUROD2.
14 Mar 2022	Intellectual disability v3.1519	NCKAP1	Ivone Leong Tag Q2_21_rating was removed from gene: NCKAP1.
14 Mar 2022	Intellectual disability v3.1519	NCDN	Ivone Leong Tag Q2_21_rating was removed from gene: NCDN.
14 Mar 2022	Intellectual disability v3.1519	MINPP1	Ivone Leong Tag Q2_21_rating was removed from gene: MINPP1.
14 Mar 2022	Intellectual disability v3.1519	MED27	Ivone Leong Tag Q2_21_rating was removed from gene: MED27.
14 Mar 2022	Intellectual disability v3.1519	MAP1B	Ivone Leong Tag Q3_21_rating was removed from gene: MAP1B.
14 Mar 2022	Intellectual disability v3.1519	LINGO4	Ivone Leong Tag Q3_21_rating was removed from gene: LINGO4.
14 Mar 2022	Intellectual disability v3.1519	KCND2	Ivone Leong Tag Q4_21_rating was removed from gene: KCND2.
14 Mar 2022	Intellectual disability v3.1519	KDM3B	Ivone Leong Tag Q2_21_rating was removed from gene: KDM3B.
14 Mar 2022	Intellectual disability v3.1519	KCNN2	Ivone Leong Tag Q2_21_rating was removed from gene: KCNN2.
14 Mar 2022	Intellectual disability v3.1519	IMPDH2	Ivone Leong Tag Q3_21_rating was removed from gene: IMPDH2.
14 Mar 2022	Intellectual disability v3.1519	HPDL	Ivone Leong Tag Q2_21_rating was removed from gene: HPDL.
14 Mar 2022	Intellectual disability v3.1519	HNMT	Ivone Leong Tag Q3_21_rating was removed from gene: HNMT. Tag Q3_21_NHS_review was removed from gene: HNMT.
14 Mar 2022	Intellectual disability v3.1519	HIST1H4C	Ivone Leong Tag Q3_21_rating was removed from gene: HIST1H4C.
14 Mar 2022	Intellectual disability v3.1519	HID1	Ivone Leong Tag Q3_21_rating was removed from gene: HID1.
14 Mar 2022	Intellectual disability v3.1519	GTF2E2	Ivone Leong Tag Q3_21_rating was removed from gene: GTF2E2.
14 Mar 2022	Intellectual disability v3.1519	GNB2	Ivone Leong Tag Q3_21_rating was removed from gene: GNB2.
14 Mar 2022	Intellectual disability v3.1519	GEMIN5	Ivone Leong Tag Q2_21_rating was removed from gene: GEMIN5.
14 Mar 2022	Intellectual disability v3.1519	GABRD	Ivone Leong Tag Q4_21_rating was removed from gene: GABRD.
14 Mar 2022	Intellectual disability v3.1519	FARSA	Ivone Leong Tag Q4_21_rating was removed from gene: FARSA.
14 Mar 2022	Intellectual disability v3.1519	FBXO31	Ivone Leong Tag Q2_21_rating was removed from gene: FBXO31.
14 Mar 2022	Intellectual disability v3.1519	ERBB4	Ivone Leong Tag Q2_21_rating was removed from gene: ERBB4. Tag Q2_21_NHS_review was removed from gene: ERBB4.
14 Mar 2022	Intellectual disability v3.1519	EMC10	Ivone Leong Tag Q2_21_rating was removed from gene: EMC10.
14 Mar 2022	Intellectual disability v3.1519	EIF5A	Ivone Leong Tag Q2_21_rating was removed from gene: EIF5A.
14 Mar 2022	Intellectual disability v3.1519	DPYSL5	Ivone Leong Tag Q3_21_rating was removed from gene: DPYSL5.
14 Mar 2022	Intellectual disability v3.1519	DPYS	Ivone Leong Tag Q2_21_expert_review was removed from gene: DPYS.
14 Mar 2022	Intellectual disability v3.1519	DPM2	Ivone Leong Tag Q2_21_rating was removed from gene: DPM2.
14 Mar 2022	Intellectual disability v3.1519	DDB1	Ivone Leong Tag Q2_21_rating was removed from gene: DDB1.
14 Mar 2022	Intellectual disability v3.1519	CAMK4	Ivone Leong Tag Q3_21_rating was removed from gene: CAMK4.
14 Mar 2022	Intellectual disability v3.1519	CLCN3	Ivone Leong Tag Q3_21_rating was removed from gene: CLCN3.
14 Mar 2022	Intellectual disability v3.1519	CHD5	Ivone Leong Tag Q3_21_rating was removed from gene: CHD5.
14 Mar 2022	Intellectual disability v3.1519	CEP85L	Ivone Leong Tag Q3_21_rating was removed from gene: CEP85L.
14 Mar 2022	Intellectual disability v3.1519	CAPN15	Ivone Leong Tag Q2_21_rating was removed from gene: CAPN15.
14 Mar 2022	Intellectual disability v3.1519	CPE	Ivone Leong Tag Q3_21_rating was removed from gene: CPE.
14 Mar 2022	Intellectual disability v3.1519	COPB2	Ivone Leong Tag Q3_21_rating was removed from gene: COPB2.
14 Mar 2022	Intellectual disability v3.1519	CTC1	Ivone Leong Tag Q3_21_rating was removed from gene: CTC1.
14 Mar 2022	Intellectual disability v3.1519	CDH15	Ivone Leong Tag watchlist was removed from gene: CDH15.
14 Mar 2022	Intellectual disability v3.1519	CDH15	Ivone Leong Tag Q4_21_rating was removed from gene: CDH15. Tag watchlist tag was added to gene: CDH15.
14 Mar 2022	Intellectual disability v3.1519	BCAS3	Ivone Leong Tag Q2_21_rating was removed from gene: BCAS3.
14 Mar 2022	Intellectual disability v3.1519	ATP9A	Ivone Leong Tag Q4_21_rating was removed from gene: ATP9A.
14 Mar 2022	Intellectual disability v3.1519	ATP1A3	Ivone Leong Tag Q3_21_expert_review was removed from gene: ATP1A3.
14 Mar 2022	Intellectual disability v3.1519	ARFGEF1	Ivone Leong Tag Q4_21_rating was removed from gene: ARFGEF1.
14 Mar 2022	Intellectual disability v3.1519	ARF1	Ivone Leong Tag Q3_21_rating was removed from gene: ARF1.
14 Mar 2022	Intellectual disability v3.1519	AP1G1	Ivone Leong Tag Q3_21_rating was removed from gene: AP1G1.
14 Mar 2022	Intellectual disability v3.1519	ANKRD17	Ivone Leong Tag Q2_21_rating was removed from gene: ANKRD17.
14 Mar 2022	Intellectual disability v3.1519	ANK2	Ivone Leong Tag Q3_21_rating was removed from gene: ANK2.
14 Mar 2022	Intellectual disability v3.1519	AGO1	Ivone Leong Tag Q2_21_expert_review was removed from gene: AGO1.
14 Mar 2022	Intellectual disability v3.1519	ABHD16A	Ivone Leong Tag Q4_21_rating was removed from gene: ABHD16A.
14 Mar 2022	Intellectual disability v3.1519	POLR3B	Ivone Leong Tag Q2_21_MOI was removed from gene: POLR3B.
14 Mar 2022	Intellectual disability v3.1519	PHF6	Ivone Leong Tag Q4_21_MOI was removed from gene: PHF6.
14 Mar 2022	Intellectual disability v3.1519	MED12	Ivone Leong Tag Q3_21_MOI was removed from gene: MED12. Tag Q3_21_expert_review was removed from gene: MED12.
14 Mar 2022	Intellectual disability v3.1519	HCCS	Ivone Leong Tag Q4_21_MOI was removed from gene: HCCS.
14 Mar 2022	Intellectual disability v3.1519	GRIK2	Ivone Leong Tag Q4_21_MOI was removed from gene: GRIK2.
14 Mar 2022	Intellectual disability v3.1519	CLPB	Ivone Leong Tag Q4_21_MOI was removed from gene: CLPB.
14 Mar 2022	Intellectual disability v3.1519	ZNF699	Sarah Leigh commented on gene: ZNF699
14 Mar 2022	Intellectual disability v3.1519	YIPF5	Sarah Leigh commented on gene: YIPF5
14 Mar 2022	Intellectual disability v3.1519	WDR4	Sarah Leigh commented on gene: WDR4
14 Mar 2022	Intellectual disability v3.1519	VPS41	Sarah Leigh commented on gene: VPS41
14 Mar 2022	Intellectual disability v3.1519	VPS11	Sarah Leigh commented on gene: VPS11
14 Mar 2022	Intellectual disability v3.1519	UFSP2	Sarah Leigh commented on gene: UFSP2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	UBE4A	Sarah Leigh commented on gene: UBE4A
14 Mar 2022	Intellectual disability v3.1519	TP73	Sarah Leigh commented on gene: TP73
14 Mar 2022	Intellectual disability v3.1519	TNPO2	Sarah Leigh commented on gene: TNPO2
14 Mar 2022	Intellectual disability v3.1519	TMEM222	Sarah Leigh commented on gene: TMEM222: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	TCF7L2	Sarah Leigh commented on gene: TCF7L2
14 Mar 2022	Intellectual disability v3.1519	SYNCRIP	Sarah Leigh commented on gene: SYNCRIP
14 Mar 2022	Intellectual disability v3.1519	SPTBN1	Sarah Leigh commented on gene: SPTBN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	SPEN	Sarah Leigh commented on gene: SPEN
14 Mar 2022	Intellectual disability v3.1519	SNIP1	Sarah Leigh commented on gene: SNIP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	SMARCA5	Sarah Leigh commented on gene: SMARCA5
14 Mar 2022	Intellectual disability v3.1519	SIN3B	Sarah Leigh commented on gene: SIN3B
14 Mar 2022	Intellectual disability v3.1519	SIAH1	Sarah Leigh commented on gene: SIAH1
14 Mar 2022	Intellectual disability v3.1519	SCYL1	Sarah Leigh commented on gene: SCYL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	SATB1	Sarah Leigh commented on gene: SATB1
14 Mar 2022	Intellectual disability v3.1519	RFX7	Sarah Leigh commented on gene: RFX7
14 Mar 2022	Intellectual disability v3.1519	RFX4	Sarah Leigh commented on gene: RFX4
14 Mar 2022	Intellectual disability v3.1519	RFX3	Sarah Leigh commented on gene: RFX3
14 Mar 2022	Intellectual disability v3.1519	PTPN4	Sarah Leigh commented on gene: PTPN4
14 Mar 2022	Intellectual disability v3.1519	PRICKLE2	Sarah Leigh commented on gene: PRICKLE2
14 Mar 2022	Intellectual disability v3.1519	POLR3B	Sarah Leigh commented on gene: POLR3B
14 Mar 2022	Intellectual disability v3.1519	PIGC	Sarah Leigh commented on gene: PIGC
14 Mar 2022	Intellectual disability v3.1519	PIDD1	Sarah Leigh commented on gene: PIDD1
14 Mar 2022	Intellectual disability v3.1519	PI4KA	Sarah Leigh commented on gene: PI4KA
14 Mar 2022	Intellectual disability v3.1519	PHF6	Sarah Leigh commented on gene: PHF6
14 Mar 2022	Intellectual disability v3.1519	PGM2L1	Sarah Leigh commented on gene: PGM2L1
14 Mar 2022	Intellectual disability v3.1519	PCDHGC4	Sarah Leigh commented on gene: PCDHGC4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	OTUD5	Sarah Leigh commented on gene: OTUD5
14 Mar 2022	Intellectual disability v3.1519	NEUROD2	Sarah Leigh commented on gene: NEUROD2
14 Mar 2022	Intellectual disability v3.1519	NCKAP1	Sarah Leigh commented on gene: NCKAP1
14 Mar 2022	Intellectual disability v3.1519	NCDN	Sarah Leigh commented on gene: NCDN
14 Mar 2022	Intellectual disability v3.1519	MINPP1	Sarah Leigh commented on gene: MINPP1
14 Mar 2022	Intellectual disability v3.1519	MED27	Sarah Leigh commented on gene: MED27
14 Mar 2022	Intellectual disability v3.1519	MED12	Sarah Leigh commented on gene: MED12
14 Mar 2022	Intellectual disability v3.1519	MAP1B	Sarah Leigh commented on gene: MAP1B
14 Mar 2022	Intellectual disability v3.1519	LINGO4	Sarah Leigh commented on gene: LINGO4
14 Mar 2022	Intellectual disability v3.1519	KDM3B	Sarah Leigh commented on gene: KDM3B
14 Mar 2022	Intellectual disability v3.1519	KCNN2	Sarah Leigh commented on gene: KCNN2
14 Mar 2022	Intellectual disability v3.1519	KCND2	Sarah Leigh commented on gene: KCND2
14 Mar 2022	Intellectual disability v3.1519	IMPDH2	Sarah Leigh commented on gene: IMPDH2
14 Mar 2022	Intellectual disability v3.1519	HPDL	Sarah Leigh commented on gene: HPDL
14 Mar 2022	Intellectual disability v3.1519	HNMT	Sarah Leigh commented on gene: HNMT
14 Mar 2022	Intellectual disability v3.1519	HIST1H4C	Sarah Leigh commented on gene: HIST1H4C
14 Mar 2022	Intellectual disability v3.1519	HID1	Sarah Leigh commented on gene: HID1
14 Mar 2022	Intellectual disability v3.1519	HCCS	Sarah Leigh commented on gene: HCCS
14 Mar 2022	Intellectual disability v3.1519	GTF2E2	Sarah Leigh commented on gene: GTF2E2
14 Mar 2022	Intellectual disability v3.1519	GRIK2	Sarah Leigh commented on gene: GRIK2
14 Mar 2022	Intellectual disability v3.1519	GNB2	Sarah Leigh commented on gene: GNB2
14 Mar 2022	Intellectual disability v3.1519	GEMIN5	Sarah Leigh commented on gene: GEMIN5
14 Mar 2022	Intellectual disability v3.1519	GABRD	Sarah Leigh commented on gene: GABRD
14 Mar 2022	Intellectual disability v3.1519	FBXO31	Sarah Leigh commented on gene: FBXO31
14 Mar 2022	Intellectual disability v3.1519	FARSA	Sarah Leigh commented on gene: FARSA
14 Mar 2022	Intellectual disability v3.1519	ERBB4	Sarah Leigh commented on gene: ERBB4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	EMC10	Sarah Leigh commented on gene: EMC10
14 Mar 2022	Intellectual disability v3.1519	EIF5A	Sarah Leigh commented on gene: EIF5A
14 Mar 2022	Intellectual disability v3.1519	DPYSL5	Sarah Leigh commented on gene: DPYSL5
14 Mar 2022	Intellectual disability v3.1519	DPYS	Sarah Leigh commented on gene: DPYS
14 Mar 2022	Intellectual disability v3.1519	DPM2	Sarah Leigh commented on gene: DPM2
14 Mar 2022	Intellectual disability v3.1519	DDB1	Sarah Leigh commented on gene: DDB1
14 Mar 2022	Intellectual disability v3.1519	CTC1	Sarah Leigh commented on gene: CTC1
14 Mar 2022	Intellectual disability v3.1519	CPE	Sarah Leigh commented on gene: CPE
14 Mar 2022	Intellectual disability v3.1519	COPB2	Sarah Leigh commented on gene: COPB2
14 Mar 2022	Intellectual disability v3.1519	CLPB	Sarah Leigh commented on gene: CLPB
14 Mar 2022	Intellectual disability v3.1519	CLCN3	Sarah Leigh commented on gene: CLCN3
14 Mar 2022	Intellectual disability v3.1519	CHD5	Sarah Leigh commented on gene: CHD5
14 Mar 2022	Intellectual disability v3.1519	CEP85L	Sarah Leigh commented on gene: CEP85L: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	CDH15	Sarah Leigh commented on gene: CDH15
14 Mar 2022	Intellectual disability v3.1519	CAPN15	Sarah Leigh commented on gene: CAPN15
14 Mar 2022	Intellectual disability v3.1519	CAMK4	Sarah Leigh commented on gene: CAMK4
14 Mar 2022	Intellectual disability v3.1519	CACNA1I	Sarah Leigh commented on gene: CACNA1I
14 Mar 2022	Intellectual disability v3.1519	BCAS3	Sarah Leigh commented on gene: BCAS3
14 Mar 2022	Intellectual disability v3.1519	ATP9A	Sarah Leigh commented on gene: ATP9A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	ATP1A3	Sarah Leigh commented on gene: ATP1A3
14 Mar 2022	Intellectual disability v3.1519	ARFGEF1	Sarah Leigh commented on gene: ARFGEF1
14 Mar 2022	Intellectual disability v3.1519	ARF1	Sarah Leigh commented on gene: ARF1
14 Mar 2022	Intellectual disability v3.1519	AP1G1	Sarah Leigh commented on gene: AP1G1
14 Mar 2022	Intellectual disability v3.1519	ANKRD17	Sarah Leigh commented on gene: ANKRD17
14 Mar 2022	Intellectual disability v3.1519	ANK2	Sarah Leigh commented on gene: ANK2
14 Mar 2022	Intellectual disability v3.1519	AGO1	Sarah Leigh commented on gene: AGO1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	AFG3L2	Sarah Leigh commented on gene: AFG3L2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Intellectual disability v3.1519	ABHD16A	Sarah Leigh commented on gene: ABHD16A
14 Mar 2022	Intellectual disability v3.1519	ZNF699	Ivone Leong Source Expert Review Green was added to ZNF699. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	YIPF5	Ivone Leong Source Expert Review Green was added to YIPF5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	WDR4	Ivone Leong Source Expert Review Green was added to WDR4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	VPS41	Ivone Leong Source Expert Review Green was added to VPS41. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	VPS11	Ivone Leong Source Expert Review Green was added to VPS11. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	UFSP2	Ivone Leong Source Expert Review Green was added to UFSP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	UBE4A	Ivone Leong Source Expert Review Green was added to UBE4A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	TP73	Ivone Leong Source Expert Review Green was added to TP73. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	TNPO2	Ivone Leong Source Expert Review Green was added to TNPO2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	TMEM222	Ivone Leong Source Expert Review Green was added to TMEM222. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	TCF7L2	Ivone Leong Source Expert Review Green was added to TCF7L2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SYNCRIP	Ivone Leong Source Expert Review Green was added to SYNCRIP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SPTBN1	Ivone Leong Source Expert Review Green was added to SPTBN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SPEN	Ivone Leong Source Expert Review Green was added to SPEN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SNIP1	Ivone Leong Source Expert Review Green was added to SNIP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SMARCA5	Ivone Leong Source Expert Review Green was added to SMARCA5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SIN3B	Ivone Leong Source Expert Review Green was added to SIN3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SIAH1	Ivone Leong Source Expert Review Green was added to SIAH1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SCYL1	Ivone Leong Source Expert Review Green was added to SCYL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	SATB1	Ivone Leong Source Expert Review Green was added to SATB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	RFX7	Ivone Leong Source Expert Review Green was added to RFX7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	RFX4	Ivone Leong Source Expert Review Green was added to RFX4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	RFX3	Ivone Leong Source Expert Review Green was added to RFX3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PTPN4	Ivone Leong Source Expert Review Green was added to PTPN4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PRICKLE2	Ivone Leong Source Expert Review Green was added to PRICKLE2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	POLR3B	Ivone Leong Source NHS GMS was added to POLR3B. Mode of inheritance for gene POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
14 Mar 2022	Intellectual disability v3.1519	PIGC	Ivone Leong Source Expert Review Green was added to PIGC. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PIDD1	Ivone Leong Source Expert Review Green was added to PIDD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PI4KA	Ivone Leong Source Expert Review Green was added to PI4KA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PHF6	Ivone Leong Source NHS GMS was added to PHF6. Mode of inheritance for gene PHF6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
14 Mar 2022	Intellectual disability v3.1519	PGM2L1	Ivone Leong Source Expert Review Green was added to PGM2L1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	PCDHGC4	Ivone Leong Source Expert Review Green was added to PCDHGC4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	OTUD5	Ivone Leong Source Expert Review Green was added to OTUD5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	NEUROD2	Ivone Leong Source Expert Review Green was added to NEUROD2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	NCKAP1	Ivone Leong Source Expert Review Green was added to NCKAP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	NCDN	Ivone Leong Source Expert Review Green was added to NCDN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	MINPP1	Ivone Leong Source Expert Review Green was added to MINPP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	MED27	Ivone Leong Source Expert Review Green was added to MED27. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	MED12	Ivone Leong Source NHS GMS was added to MED12. Mode of inheritance for gene MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
14 Mar 2022	Intellectual disability v3.1519	MAP1B	Ivone Leong Source Expert Review Green was added to MAP1B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	LINGO4	Ivone Leong Source Expert Review Green was added to LINGO4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	KDM3B	Ivone Leong Source Expert Review Green was added to KDM3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	KCNN2	Ivone Leong Source Expert Review Green was added to KCNN2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	KCND2	Ivone Leong Source Expert Review Green was added to KCND2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	IMPDH2	Ivone Leong Source Expert Review Green was added to IMPDH2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	HPDL	Ivone Leong Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	HNMT	Ivone Leong Source Expert Review Green was added to HNMT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	HIST1H4C	Ivone Leong Source Expert Review Green was added to HIST1H4C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	HID1	Ivone Leong Source Expert Review Green was added to HID1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	HCCS	Ivone Leong Source NHS GMS was added to HCCS. Mode of inheritance for gene HCCS was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
14 Mar 2022	Intellectual disability v3.1519	GTF2E2	Ivone Leong Source Expert Review Green was added to GTF2E2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	GRIK2	Ivone Leong Source NHS GMS was added to GRIK2. Mode of inheritance for gene GRIK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
14 Mar 2022	Intellectual disability v3.1519	GNB2	Ivone Leong Source Expert Review Green was added to GNB2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	GEMIN5	Ivone Leong Source Expert Review Green was added to GEMIN5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	GABRD	Ivone Leong Source Expert Review Green was added to GABRD. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	FBXO31	Ivone Leong Source Expert Review Green was added to FBXO31. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	FARSA	Ivone Leong Source Expert Review Green was added to FARSA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ERBB4	Ivone Leong Source Expert Review Green was added to ERBB4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	EMC10	Ivone Leong Source Expert Review Green was added to EMC10. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	EIF5A	Ivone Leong Source Expert Review Green was added to EIF5A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	DPYSL5	Ivone Leong Source Expert Review Green was added to DPYSL5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	DPYS	Ivone Leong Source Expert Review Green was added to DPYS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	DPM2	Ivone Leong Source Expert Review Green was added to DPM2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	DDB1	Ivone Leong Source Expert Review Green was added to DDB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CTC1	Ivone Leong Source Expert Review Amber was added to CTC1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Intellectual disability v3.1519	CPE	Ivone Leong Source Expert Review Green was added to CPE. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	COPB2	Ivone Leong Source Expert Review Green was added to COPB2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CLPB	Ivone Leong Source NHS GMS was added to CLPB. Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
14 Mar 2022	Intellectual disability v3.1519	CLCN3	Ivone Leong Source Expert Review Green was added to CLCN3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CHD5	Ivone Leong Source Expert Review Green was added to CHD5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CEP85L	Ivone Leong Source Expert Review Green was added to CEP85L. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CDH15	Ivone Leong Source Expert Review Red was added to CDH15. Rating Changed from Green List (high evidence) to Red List (low evidence)
14 Mar 2022	Intellectual disability v3.1519	CAPN15	Ivone Leong Source Expert Review Green was added to CAPN15. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CAMK4	Ivone Leong Source Expert Review Green was added to CAMK4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	CACNA1I	Ivone Leong Source Expert Review Green was added to CACNA1I. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	BCAS3	Ivone Leong Source Expert Review Green was added to BCAS3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ATP9A	Ivone Leong Source Expert Review Green was added to ATP9A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ATP1A3	Ivone Leong Source Expert Review Green was added to ATP1A3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ARFGEF1	Ivone Leong Source Expert Review Green was added to ARFGEF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ARF1	Ivone Leong Source Expert Review Green was added to ARF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	AP1G1	Ivone Leong Source Expert Review Green was added to AP1G1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ANKRD17	Ivone Leong Source Expert Review Green was added to ANKRD17. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	ANK2	Ivone Leong Source Expert Review Green was added to ANK2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	AGO1	Ivone Leong Source Expert Review Green was added to AGO1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Intellectual disability v3.1519	AFG3L2	Ivone Leong Source NHS GMS was added to AFG3L2.
14 Mar 2022	Intellectual disability v3.1519	ABHD16A	Ivone Leong Source Expert Review Green was added to ABHD16A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Lysosomal storage disorder v1.78	VPS16	Ivone Leong Tag Q2_21_rating was removed from gene: VPS16. Tag Q2_21_MOI was removed from gene: VPS16.
14 Mar 2022	Lysosomal storage disorder v1.78	VPS16	Sarah Leigh commented on gene: VPS16
14 Mar 2022	Lysosomal storage disorder v1.77	VPS16	Ivone Leong Source Expert Review Green was added to VPS16. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Familial chylomicronaemia syndrome (FCS) v1.21	APOB	Ivone Leong Tag Q3_21_NHS_review was removed from gene: APOB. Tag Q3_21_expert_review was removed from gene: APOB.
14 Mar 2022	Familial chylomicronaemia syndrome (FCS) v1.21	APOB	Sarah Leigh commented on gene: APOB: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Familial chylomicronaemia syndrome (FCS) v1.20	APOB	Ivone Leong Source Expert Review Red was added to APOB. Rating Changed from Green List (high evidence) to Red List (low evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	TARS2	Ivone Leong Tag Q4_21_rating was removed from gene: TARS2.
14 Mar 2022	Likely inborn error of metabolism v2.229	POMK	Ivone Leong Tag Q2_21_rating was removed from gene: POMK.
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFC2	Ivone Leong Tag Q2_21_rating was removed from gene: NDUFC2.
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFA12	Ivone Leong Tag Q2_21_rating was removed from gene: NDUFA12.
14 Mar 2022	Likely inborn error of metabolism v2.229	GALNT2	Ivone Leong Tag Q2_21_rating was removed from gene: GALNT2.
14 Mar 2022	Likely inborn error of metabolism v2.229	EOGT	Ivone Leong Tag Q2_21_rating was removed from gene: EOGT.
14 Mar 2022	Likely inborn error of metabolism v2.229	EHBP1L1	Ivone Leong Tag Q4_21_rating was removed from gene: EHBP1L1.
14 Mar 2022	Likely inborn error of metabolism v2.229	CSGALNACT1	Ivone Leong Tag Q2_21_rating was removed from gene: CSGALNACT1.
14 Mar 2022	Likely inborn error of metabolism v2.229	B4GALNT1	Ivone Leong Tag Q2_21_rating was removed from gene: B4GALNT1.
14 Mar 2022	Likely inborn error of metabolism v2.229	FAR1	Ivone Leong Tag Q2_21_rating was removed from gene: FAR1.
14 Mar 2022	Likely inborn error of metabolism v2.229	CLPB	Ivone Leong Tag Q4_21_MOI was removed from gene: CLPB.
14 Mar 2022	Likely inborn error of metabolism v2.229	NAXD	Ivone Leong Tag Q2_21_rating was removed from gene: NAXD.
14 Mar 2022	Likely inborn error of metabolism v2.229	NAXD	Sarah Leigh commented on gene: NAXD
14 Mar 2022	Likely inborn error of metabolism v2.229	TARS2	Sarah Leigh commented on gene: TARS2: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	POMK	Sarah Leigh commented on gene: POMK: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFC2	Sarah Leigh commented on gene: NDUFC2: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFA12	Sarah Leigh commented on gene: NDUFA12: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	GALNT2	Sarah Leigh commented on gene: GALNT2: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	FAR1	Sarah Leigh commented on gene: FAR1
14 Mar 2022	Likely inborn error of metabolism v2.229	EOGT	Sarah Leigh commented on gene: EOGT: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	EHBP1L1	Sarah Leigh commented on gene: EHBP1L1: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	CSGALNACT1	Sarah Leigh commented on gene: CSGALNACT1
14 Mar 2022	Likely inborn error of metabolism v2.229	CLPB	Sarah Leigh commented on gene: CLPB
14 Mar 2022	Likely inborn error of metabolism v2.229	B4GALNT1	Sarah Leigh commented on gene: B4GALNT1: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Likely inborn error of metabolism v2.229	NAXD	Ivone Leong Source Expert Review Green was added to NAXD. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	TARS2	Ivone Leong Source Expert Review Green was added to TARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	POMK	Ivone Leong Source Expert Review Green was added to POMK. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFC2	Ivone Leong Source Expert Review Green was added to NDUFC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	NDUFA12	Ivone Leong Source Expert Review Green was added to NDUFA12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	GALNT2	Ivone Leong Source Expert Review Green was added to GALNT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	FAR1	Ivone Leong Source Expert Review Red was added to FAR1. Rating Changed from Green List (high evidence) to Red List (low evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	EOGT	Ivone Leong Source Expert Review Green was added to EOGT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	EHBP1L1	Ivone Leong Source Expert Review Green was added to EHBP1L1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	CSGALNACT1	Ivone Leong Source Expert Review Green was added to CSGALNACT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Likely inborn error of metabolism v2.229	CLPB	Ivone Leong Source NHS GMS was added to CLPB. Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
14 Mar 2022	Likely inborn error of metabolism v2.229	B4GALNT1	Ivone Leong Source Expert Review Green was added to B4GALNT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.224	FIG4	Ivone Leong Tag Q2_21_rating was removed from gene: FIG4.
14 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.224	FIG4	Sarah Leigh commented on gene: FIG4
14 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.224	FIG4	Ivone Leong Source Expert Review Green was added to FIG4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.127	B4GAT1	Ivone Leong Tag Q3_21_rating was removed from gene: B4GAT1.
14 Mar 2022	Hydrocephalus v2.127	EEF2	Ivone Leong Tag Q2_21_rating was removed from gene: EEF2.
14 Mar 2022	Hydrocephalus v2.127	KIDINS220	Ivone Leong Tag deletions was removed from gene: KIDINS220.
14 Mar 2022	Hydrocephalus v2.127	KIDINS220	Ivone Leong Tag Q2_21_rating was removed from gene: KIDINS220. Tag deletions tag was added to gene: KIDINS220.
14 Mar 2022	Hydrocephalus v2.127	MPDZ	Ivone Leong Tag Q2_21_rating was removed from gene: MPDZ.
14 Mar 2022	Hydrocephalus v2.127	SMARCC1	Ivone Leong Tag Q2_21_rating was removed from gene: SMARCC1.
14 Mar 2022	Hydrocephalus v2.127	TBC1D32	Ivone Leong Tag Q4_21_rating was removed from gene: TBC1D32.
14 Mar 2022	Hydrocephalus v2.127	TCIRG1	Ivone Leong Tag Q4_21_rating was removed from gene: TCIRG1.
14 Mar 2022	Hydrocephalus v2.127	TNFRSF11A	Ivone Leong Tag Q4_21_rating was removed from gene: TNFRSF11A.
14 Mar 2022	Hydrocephalus v2.127	TRIM71	Ivone Leong Tag Q2_21_rating was removed from gene: TRIM71.
14 Mar 2022	Hydrocephalus v2.127	TRIM71	Sarah Leigh commented on gene: TRIM71
14 Mar 2022	Hydrocephalus v2.127	TNFRSF11A	Sarah Leigh commented on gene: TNFRSF11A
14 Mar 2022	Hydrocephalus v2.127	TCIRG1	Sarah Leigh commented on gene: TCIRG1
14 Mar 2022	Hydrocephalus v2.127	TBC1D32	Sarah Leigh commented on gene: TBC1D32
14 Mar 2022	Hydrocephalus v2.127	SMARCC1	Sarah Leigh commented on gene: SMARCC1
14 Mar 2022	Hydrocephalus v2.127	MPDZ	Sarah Leigh commented on gene: MPDZ
14 Mar 2022	Hydrocephalus v2.127	KIDINS220	Sarah Leigh commented on gene: KIDINS220
14 Mar 2022	Hydrocephalus v2.127	EEF2	Sarah Leigh commented on gene: EEF2
14 Mar 2022	Hydrocephalus v2.127	B4GAT1	Sarah Leigh commented on gene: B4GAT1
14 Mar 2022	Hydrocephalus v2.126	TRIM71	Ivone Leong Source Expert Review Green was added to TRIM71. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	TNFRSF11A	Ivone Leong Source Expert Review Green was added to TNFRSF11A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	TCIRG1	Ivone Leong Source Expert Review Green was added to TCIRG1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	TBC1D32	Ivone Leong Source Expert Review Green was added to TBC1D32. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	SMARCC1	Ivone Leong Source Expert Review Green was added to SMARCC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	MPDZ	Ivone Leong Source Expert Review Green was added to MPDZ. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	KIDINS220	Ivone Leong Source Expert Review Green was added to KIDINS220. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	EEF2	Ivone Leong Source Expert Review Green was added to EEF2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hydrocephalus v2.126	B4GAT1	Ivone Leong Source Expert Review Green was added to B4GAT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Holoprosencephaly v2.27	KMT2D	Ivone Leong Tag Q3_21_rating was removed from gene: KMT2D.
14 Mar 2022	Holoprosencephaly v2.27	RAD21	Ivone Leong Tag Q3_21_rating was removed from gene: RAD21.
14 Mar 2022	Holoprosencephaly v2.27	RAD21	Sarah Leigh commented on gene: RAD21
14 Mar 2022	Holoprosencephaly v2.27	KMT2D	Sarah Leigh commented on gene: KMT2D
14 Mar 2022	Holoprosencephaly v2.26	RAD21	Ivone Leong Source Expert Review Green was added to RAD21. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Holoprosencephaly v2.26	KMT2D	Ivone Leong Source Expert Review Green was added to KMT2D. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	SLC25A15	Ivone Leong Tag Q3_21_rating was removed from gene: SLC25A15.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	RNASEH2B	Ivone Leong Tag Q4_21_rating was removed from gene: RNASEH2B.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	MAPK8IP3	Ivone Leong Tag Q4_21_rating was removed from gene: MAPK8IP3.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	IFIH1	Ivone Leong Tag Q4_21_rating was removed from gene: IFIH1.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HPDL	Ivone Leong Tag Q2_21_rating was removed from gene: HPDL. Tag Q2_21_NHS_review was removed from gene: HPDL.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HIKESHI	Ivone Leong Tag Q2_21_rating was removed from gene: HIKESHI.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GPT2	Ivone Leong Tag Q4_21_rating was removed from gene: GPT2.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GLRX5	Ivone Leong Tag Q2_21_rating was removed from gene: GLRX5.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GJA1	Ivone Leong Tag Q3_21_rating was removed from gene: GJA1.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GALC	Ivone Leong Tag Q3_21_rating was removed from gene: GALC.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	FAR1	Ivone Leong Tag Q2_21_rating was removed from gene: FAR1.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ELOVL1	Ivone Leong Tag Q4_21_rating was removed from gene: ELOVL1.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	BCAS3	Ivone Leong Tag Q2_21_rating was removed from gene: BCAS3.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ARL6IP1	Ivone Leong Tag Q2_21_rating was removed from gene: ARL6IP1.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ALDH3A2	Ivone Leong Tag Q3_21_rating was removed from gene: ALDH3A2.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	AFG3L2	Ivone Leong Tag Q2_21_MOI was removed from gene: AFG3L2.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	SLC25A15	Sarah Leigh commented on gene: SLC25A15
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	RNASEH2B	Sarah Leigh commented on gene: RNASEH2B
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	MAPK8IP3	Sarah Leigh commented on gene: MAPK8IP3
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	IFIH1	Sarah Leigh commented on gene: IFIH1
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HPDL	Sarah Leigh commented on gene: HPDL: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HPDL	Sarah Leigh commented on gene: HPDL: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HPDL	Sarah Leigh commented on gene: HPDL
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	HIKESHI	Sarah Leigh commented on gene: HIKESHI
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GPT2	Sarah Leigh commented on gene: GPT2
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GLRX5	Sarah Leigh commented on gene: GLRX5
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GJA1	Sarah Leigh commented on gene: GJA1
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	GALC	Sarah Leigh commented on gene: GALC
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	FAR1	Sarah Leigh commented on gene: FAR1
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ELOVL1	Sarah Leigh commented on gene: ELOVL1
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	BCAS3	Sarah Leigh commented on gene: BCAS3
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ARL6IP1	Sarah Leigh commented on gene: ARL6IP1
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	ALDH3A2	Sarah Leigh commented on gene: ALDH3A2
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.130	AFG3L2	Sarah Leigh commented on gene: AFG3L2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	SLC25A15	Ivone Leong Source Expert Review Green was added to SLC25A15. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	RNASEH2B	Ivone Leong Source Expert Review Green was added to RNASEH2B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	MAPK8IP3	Ivone Leong Source Expert Review Green was added to MAPK8IP3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	IFIH1	Ivone Leong Source Expert Review Green was added to IFIH1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	HPDL	Ivone Leong Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	HIKESHI	Ivone Leong Source Expert Review Green was added to HIKESHI. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	GPT2	Ivone Leong Source Expert Review Green was added to GPT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	GLRX5	Ivone Leong Source Expert Review Green was added to GLRX5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	GJA1	Ivone Leong Source Expert Review Green was added to GJA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	GALC	Ivone Leong Source Expert Review Green was added to GALC. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	FAR1	Ivone Leong Source Expert Review Green was added to FAR1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	ELOVL1	Ivone Leong Source Expert Review Green was added to ELOVL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	BCAS3	Ivone Leong Source Expert Review Green was added to BCAS3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	ARL6IP1	Ivone Leong Source Expert Review Green was added to ARL6IP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	ALDH3A2	Ivone Leong Source Expert Review Green was added to ALDH3A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset hereditary spastic paraplegia v2.129	AFG3L2	Ivone Leong Mode of inheritance for gene AFG3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	WDR45B	Ivone Leong Tag Q3_21_phenotype was removed from gene: WDR45B.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	UCHL1	Ivone Leong Tag Q2_21_expert_review was removed from gene: UCHL1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	TFG	Ivone Leong Tag Q3_21_phenotype was removed from gene: TFG.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SPART	Ivone Leong Tag Q3_21_phenotype was removed from gene: SPART.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC1A4	Ivone Leong Tag Q2_21_phenotype was removed from gene: SLC1A4.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC16A2	Ivone Leong Tag Q3_21_phenotype was removed from gene: SLC16A2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SERAC1	Ivone Leong Tag Q3_21_phenotype was removed from gene: SERAC1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	REEP2	Ivone Leong Tag Q3_21_phenotype was removed from gene: REEP2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	NT5C2	Ivone Leong Tag Q3_21_phenotype was removed from gene: NT5C2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	NKX6-2	Ivone Leong Tag Q3_21_phenotype was removed from gene: NKX6-2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	L1CAM	Ivone Leong Tag Q3_21_phenotype was removed from gene: L1CAM.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	KIDINS220	Ivone Leong Tag Q3_21_phenotype was removed from gene: KIDINS220.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	KDM5C	Ivone Leong Tag Q3_21_expert_review was removed from gene: KDM5C. Tag Q3_21_phenotype was removed from gene: KDM5C.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	HACE1	Ivone Leong Tag Q3_21_phenotype was removed from gene: HACE1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC25A15	Ivone Leong Tag Q3_21_rating was removed from gene: SLC25A15.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GJA1	Ivone Leong Tag Q3_21_rating was removed from gene: GJA1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GBE1	Ivone Leong Tag Q3_21_rating was removed from gene: GBE1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GALC	Ivone Leong Tag Q3_21_rating was removed from gene: GALC.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	FBXO7	Ivone Leong Tag Q3_21_rating was removed from gene: FBXO7.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	FARS2	Ivone Leong Tag Q3_21_phenotype was removed from gene: FARS2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ERLIN1	Ivone Leong Tag Q3_21_phenotype was removed from gene: ERLIN1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ENTPD1	Ivone Leong Tag Q3_21_phenotype was removed from gene: ENTPD1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	CYP2U1	Ivone Leong Tag Q2_21_expert_review was removed from gene: CYP2U1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	CPT1C	Ivone Leong Tag Q4_21_rating was removed from gene: CPT1C.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	C12orf65	Ivone Leong Tag Q3_21_expert_review was removed from gene: C12orf65. Tag Q3_21_phenotype was removed from gene: C12orf65.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ARG1	Ivone Leong Tag Q3_21_phenotype was removed from gene: ARG1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ALS2	Ivone Leong Tag Q3_21_expert_review was removed from gene: ALS2. Tag Q3_21_phenotype was removed from gene: ALS2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AIMP1	Ivone Leong Tag Q3_21_phenotype was removed from gene: AIMP1.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AFG3L2	Ivone Leong Tag Q2_21_phenotype was removed from gene: AFG3L2. Tag Q2_21_MOI was removed from gene: AFG3L2.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	WDR45B	Sarah Leigh commented on gene: WDR45B
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	UCHL1	Sarah Leigh commented on gene: UCHL1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	TFG	Sarah Leigh commented on gene: TFG
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SPART	Sarah Leigh commented on gene: SPART
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC25A15	Sarah Leigh commented on gene: SLC25A15
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC1A4	Sarah Leigh commented on gene: SLC1A4
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SLC16A2	Sarah Leigh commented on gene: SLC16A2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	SERAC1	Sarah Leigh commented on gene: SERAC1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	REEP2	Sarah Leigh commented on gene: REEP2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	NT5C2	Sarah Leigh commented on gene: NT5C2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	NKX6-2	Sarah Leigh commented on gene: NKX6-2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	L1CAM	Sarah Leigh commented on gene: L1CAM
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	KIDINS220	Sarah Leigh commented on gene: KIDINS220
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	KDM5C	Sarah Leigh commented on gene: KDM5C
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	HACE1	Sarah Leigh commented on gene: HACE1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GJA1	Sarah Leigh commented on gene: GJA1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GBE1	Sarah Leigh commented on gene: GBE1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	GALC	Sarah Leigh commented on gene: GALC
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	FBXO7	Sarah Leigh commented on gene: FBXO7
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	FARS2	Sarah Leigh commented on gene: FARS2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ERLIN1	Sarah Leigh commented on gene: ERLIN1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ENTPD1	Sarah Leigh commented on gene: ENTPD1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	CYP2U1	Sarah Leigh commented on gene: CYP2U1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	CPT1C	Sarah Leigh commented on gene: CPT1C
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	C12orf65	Sarah Leigh commented on gene: C12orf65
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ARG1	Sarah Leigh commented on gene: ARG1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	ALS2	Sarah Leigh commented on gene: ALS2
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AIMP1	Sarah Leigh commented on gene: AIMP1
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.95	AFG3L2	Sarah Leigh commented on gene: AFG3L2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	WDR45B	Ivone Leong Source Expert Review Amber was added to WDR45B. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	UCHL1	Ivone Leong Source Expert Review Amber was added to UCHL1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	TFG	Ivone Leong Source Expert Review Amber was added to TFG. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	SPART	Ivone Leong Source Expert Review Amber was added to SPART. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	SLC25A15	Ivone Leong Source Expert Review Green was added to SLC25A15. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	SLC1A4	Ivone Leong Source Expert Review Amber was added to SLC1A4. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	SLC16A2	Ivone Leong Source Expert Review Amber was added to SLC16A2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	SERAC1	Ivone Leong Source Expert Review Amber was added to SERAC1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	REEP2	Ivone Leong Source Expert Review Amber was added to REEP2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	NT5C2	Ivone Leong Source Expert Review Amber was added to NT5C2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	NKX6-2	Ivone Leong Source Expert Review Amber was added to NKX6-2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	L1CAM	Ivone Leong Source Expert Review Amber was added to L1CAM. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	KIDINS220	Ivone Leong Source Expert Review Amber was added to KIDINS220. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	KDM5C	Ivone Leong Source Expert Review Amber was added to KDM5C. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	HACE1	Ivone Leong Source Expert Review Amber was added to HACE1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	GJA1	Ivone Leong Source Expert Review Green was added to GJA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	GBE1	Ivone Leong Source Expert Review Green was added to GBE1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	GALC	Ivone Leong Source Expert Review Green was added to GALC. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	FBXO7	Ivone Leong Source Expert Review Green was added to FBXO7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	FARS2	Ivone Leong Source Expert Review Amber was added to FARS2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	ERLIN1	Ivone Leong Source Expert Review Amber was added to ERLIN1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	ENTPD1	Ivone Leong Source Expert Review Amber was added to ENTPD1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	CYP2U1	Ivone Leong Source Expert Review Amber was added to CYP2U1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	CPT1C	Ivone Leong Source Expert Review Green was added to CPT1C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	C12orf65	Ivone Leong Source Expert Review Amber was added to C12orf65. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	ARG1	Ivone Leong Source Expert Review Amber was added to ARG1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	ALS2	Ivone Leong Source Expert Review Amber was added to ALS2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	AIMP1	Ivone Leong Source Expert Review Amber was added to AIMP1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Adult onset hereditary spastic paraplegia v1.94	AFG3L2	Ivone Leong Source Expert Review Amber was added to AFG3L2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	VWA1	Ivone Leong Tag Q3_21_rating was removed from gene: VWA1. Tag Q3_21_NHS_review was removed from gene: VWA1.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	POLR3B	Ivone Leong Tag Q2_21_rating was removed from gene: POLR3B.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	PIGB	Ivone Leong Tag Q3_21_rating was removed from gene: PIGB.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	HEXB	Ivone Leong Tag Q4_21_rating was removed from gene: HEXB.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	HEXA	Ivone Leong Tag Q4_21_rating was removed from gene: HEXA.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	MME	Ivone Leong Tag Q4_21_expert_review was removed from gene: MME. Tag Q4_21_MOI was removed from gene: MME. Tag Q4_21_NHS_review was removed from gene: MME.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	GSN	Ivone Leong Tag Q3_21_rating was removed from gene: GSN.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	C1orf194	Ivone Leong Tag Q3_21_rating was removed from gene: C1orf194. Tag Q3_21_NHS_review was removed from gene: C1orf194.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	VWA1	Sarah Leigh commented on gene: VWA1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	POLR3B	Sarah Leigh commented on gene: POLR3B
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	PIGB	Sarah Leigh commented on gene: PIGB
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	MME	Sarah Leigh commented on gene: MME
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	HEXB	Sarah Leigh commented on gene: HEXB
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	HEXA	Sarah Leigh commented on gene: HEXA
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	GSN	Sarah Leigh commented on gene: GSN
14 Mar 2022	Hereditary neuropathy or pain disorder v1.88	C1orf194	Sarah Leigh commented on gene: C1orf194: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	VWA1	Ivone Leong Source Expert Review Green was added to VWA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	POLR3B	Ivone Leong Source Expert Review Green was added to POLR3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	PIGB	Ivone Leong Source Expert Review Green was added to PIGB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	MME	Ivone Leong Mode of inheritance for gene MME was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	HEXB	Ivone Leong Source Expert Review Green was added to HEXB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	HEXA	Ivone Leong Source Expert Review Green was added to HEXA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	GSN	Ivone Leong Source Expert Review Green was added to GSN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Hereditary neuropathy or pain disorder v1.87	C1orf194	Ivone Leong Source Expert Review Green was added to C1orf194. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	VPS41	Sarah Leigh commented on gene: VPS41: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	VPS16	Sarah Leigh commented on gene: VPS16: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	UBTF	Sarah Leigh commented on gene: UBTF: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	TARS2	Sarah Leigh commented on gene: TARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	SLC16A2	Sarah Leigh commented on gene: SLC16A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	SCN1A	Sarah Leigh commented on gene: SCN1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	MED27	Sarah Leigh commented on gene: MED27: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	IRF2BPL	Sarah Leigh commented on gene: IRF2BPL: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	IMPDH2	Sarah Leigh commented on gene: IMPDH2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	HPRT1	Sarah Leigh commented on gene: HPRT1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	GRIN1	Sarah Leigh commented on gene: GRIN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	GNB1	Sarah Leigh commented on gene: GNB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	GLRB	Sarah Leigh commented on gene: GLRB: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	FUCA1	Sarah Leigh commented on gene: FUCA1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	FOXG1	Sarah Leigh commented on gene: FOXG1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	FITM2	Sarah Leigh commented on gene: FITM2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	DHDDS	Sarah Leigh commented on gene: DHDDS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	CSTB	Sarah Leigh commented on gene: CSTB: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	CLPB	Sarah Leigh commented on gene: CLPB: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	CAMK4	Sarah Leigh commented on gene: CAMK4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	C9orf72	Sarah Leigh commented on gene: C9orf72: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.217	ALDH18A1	Sarah Leigh commented on gene: ALDH18A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
14 Mar 2022	Dilated Cardiomyopathy and conduction defects v1.75	LDB3	Matthew Edwards reviewed gene: LDB3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 4662268, PMID: 14660611, PMID: 16427346; Phenotypes: Cardiomyopathy, dilated, 1C, with or without LVNC (OMIM #601493); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
14 Mar 2022	Early onset or syndromic epilepsy v2.498	CPSF3	Konstantinos Varvagiannis gene: CPSF3 was added gene: CPSF3 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPSF3 were set to 35121750 Phenotypes for gene: CPSF3 were set to Failure to thrive; Abnormal muscle tone; Global developmental delay; Intellectual disability; Microcephaly; Seizures Penetrance for gene: CPSF3 were set to Complete Review for gene: CPSF3 was set to AMBER Added comment: Arnadottir (2022 - PMID: 35121750) describe the phenotype associated with biallelic CPSF3 pathogenic variants. Based on WGS of 56,969 Icelanders and imputing the genotype of another 153,054 chip-genotyped Icelanders, the authors identified missense variants with a deficit of homozygous carriers to what would be expected based on AF. (For variants with MAF>0.4%, for which >=3 hmz carriers would be expected by H-W equilibrium, no identified hmz carriers within this cohort/dataset). A total of 114 such missense variants was identified. 5 of these SNVs, among which a CPSF3 one (NM_016207.3:c.1403G>A / p.Gly468Glu), were however observed in a series of 764 individuals investigated with clinical WGS at the National University Hospital. The CPSF3 variant with a MAF of 0.41% (3 hmz expected but none observed in the population set) was found in homozygosity in 2 closely related individuals, both investigated for FTT, severe DD, ID, microcephaly, seizures but remaining unresolved following WGS with no other candidate variants. Using genealogical information from the db of deCODE genetics, the authors identified 3 couples from the 153k genotyped Icelanders where both partners were htz carriers for this SNV. These 3 couples had 10 offspring, 4 of whom deceased but with the same phenotypic features as above (hypotonia 4/4, ID 4/4, seizures 3/4, microcephaly 2/4). Paraffin embedded samples of 2 of these children and WG & Sanger sequencing confirmed hmz for Gly468Glu in 2 sibs, without other candidate variants. Samples of the 2 other individuals were N/A. Through GeneMatcher 2 additional first-cousin patients from Mexico were identified, being hmz for another CPSF3 variant (c.1061T>C/p.Ile354Thr) and having overlapping phenotype of abnormal muscle tone, ID, seizures and microcephaly. There were no other variants in WES analysis. mRNA studies in WBCs from Gly468Glu htz carriers did not reveal reduced levels and W.Blot of lymphocytes from a hmz individual confirmed expression, overall suggesting that the variant does not affect the protein levels but presumably the function. CPSF3 encodes cleavage and polyadenylation specificity factor 3, a 684 aa protein, subunit of the cleavage and polyadenylation specificity factor compex. As discussed, cleavage and polyadenylation of the 3' of pre-mRNAs is necessary before transport out of the nucleus with CPSF playing a crucial role in the process of cleavage. CPSF3 ko mice exhibit embryonic lethality, while in yeast mutations in key residues of the CPSF3 homolog are lethal. In gnomAD, CPSF3 has a pLI of 0, z-score of 3.61 with no homozygotes for pLoF variants in 141k individuals (or ~57k WGS Icelanders). The 2 missense variants concern highly conserved residues (GERP ~5.8). Both are hypothesized to affect the ability of the protein to bind other factors involved in pre-mRNA cleavage. Overall the authors speculate that not only complete loss of CPSF3 would result in drastic phenotypic effects - as in the murine model - but also variants altering its enzymatic function. There is currently no CPSF3-related phenotype in OMIM, G2P, SysID, The gene is included with green rating in the ID, epilepsy and microcephaly panels in PanelApp Australia. Consider inclusion probably with amber rating (Highly consistent phenotype, biological function, evidence from animal models. 2 identified variants, authors state that follow-up functional studies are needed). Also consider inclusion in other possibly relevant panels. Sources: Literature
14 Mar 2022	Intellectual disability v3.1518	CPSF3	Konstantinos Varvagiannis gene: CPSF3 was added gene: CPSF3 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPSF3 were set to 35121750 Phenotypes for gene: CPSF3 were set to Failure to thrive; Abnormal muscle tone; Global developmental delay; Intellectual disability; Microcephaly; Seizures Penetrance for gene: CPSF3 were set to Complete Review for gene: CPSF3 was set to AMBER Added comment: Arnadottir (2022 - PMID: 35121750) describe the phenotype associated with biallelic CPSF3 pathogenic variants. Based on WGS of 56,969 Icelanders and imputing the genotype of another 153,054 chip-genotyped Icelanders, the authors identified missense variants with a deficit of homozygous carriers to what would be expected based on AF. (For variants with MAF>0.4%, for which >=3 hmz carriers would be expected by H-W equilibrium, no identified hmz carriers within this cohort/dataset). A total of 114 such missense variants was identified. 5 of these SNVs, among which a CPSF3 one (NM_016207.3:c.1403G>A / p.Gly468Glu), were however observed in a series of 764 individuals investigated with clinical WGS at the National University Hospital. The CPSF3 variant with a MAF of 0.41% (3 hmz expected but none observed in the population set) was found in homozygosity in 2 closely related individuals, both investigated for FTT, severe DD, ID, microcephaly, seizures but remaining unresolved following WGS with no other candidate variants. Using genealogical information from the db of deCODE genetics, the authors identified 3 couples from the 153k genotyped Icelanders where both partners were htz carriers for this SNV. These 3 couples had 10 offspring, 4 of whom deceased but with the same phenotypic features as above (hypotonia 4/4, ID 4/4, seizures 3/4, microcephaly 2/4). Paraffin embedded samples of 2 of these children and WG & Sanger sequencing confirmed hmz for Gly468Glu in 2 sibs, without other candidate variants. Samples of the 2 other individuals were N/A. Through GeneMatcher 2 additional first-cousin patients from Mexico were identified, being hmz for another CPSF3 variant (c.1061T>C/p.Ile354Thr) and having overlapping phenotype of abnormal muscle tone, ID, seizures and microcephaly. There were no other variants in WES analysis. mRNA studies in WBCs from Gly468Glu htz carriers did not reveal reduced levels and W.Blot of lymphocytes from a hmz individual confirmed expression, overall suggesting that the variant does not affect the protein levels but presumably the function. CPSF3 encodes cleavage and polyadenylation specificity factor 3, a 684 aa protein, subunit of the cleavage and polyadenylation specificity factor compex. As discussed, cleavage and polyadenylation of the 3' of pre-mRNAs is necessary before transport out of the nucleus with CPSF playing a crucial role in the process of cleavage. CPSF3 ko mice exhibit embryonic lethality, while in yeast mutations in key residues of the CPSF3 homolog are lethal. In gnomAD, CPSF3 has a pLI of 0, z-score of 3.61 with no homozygotes for pLoF variants in 141k individuals (or ~57k WGS Icelanders). The 2 missense variants concerned highly conserved residues (GERP ~5.8). Both are hypothesized to affect the ability of the protein to bind other factors involved in pre-mRNA cleavage. Overall the authors speculate that not only complete loss of CPSF3 would result in drastic phenotypic effects - as in the murine model - but also variants altering its enzymatic function. There is currently no CPSF3-related phenotype in OMIM, G2P, SysID, The gene is included with green rating in the ID, epilepsy and microcephaly panels in PanelApp Australia. Consider inclusion probably with amber rating (Highly consistent phenotype, biological function, evidence from animal models. 2 identified variants, authors state that follow-up functional studies are needed). Also consider inclusion in other possibly relevant panels. Sources: Literature
13 Mar 2022	Intellectual disability v3.1518	NRCAM	Konstantinos Varvagiannis gene: NRCAM was added gene: NRCAM was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRCAM were set to 35108495 Phenotypes for gene: NRCAM were set to Hypotonia; Hypertonia; Spasticity; Global developmental delay; Intellectual disability; Microcephaly; Behavioral abnormality; Neuropathy; Hearing abnormality; Abnormality of the eye; Abnormality of the skeletal system; Scoliosis; Abnormality of the face Penetrance for gene: NRCAM were set to Complete Review for gene: NRCAM was set to GREEN Added comment: Kurolap et al (2022 - PMID: 35108495) describe the phenotype of 10 individuals (from 8 families) with biallelic variants in NRCAM. Features included tone abnormalities (hypotonia in 4/10, hypertonia/spasticity in 4/10), DD (8/10 - 7 families) and cognitive impairment (in 7/10 - 6 fam), neuropathy (4/10 - incl. 2 sibs without DD/ID). Other phenotypes incl. FTT (2/8), microcephaly (3/6), variable behavioral issues (3/5), abnormalities from the eyes/vision (6/8 - cataract in 2), abnormal hearing (3/7) or skeletal findings (8/9 - incl. scoliosis in 5). Nonspecific facial features were reported in 5/8. Previous metabolic, genetic (incl. karyotype or CMA, FMR1, testing for Steinert disease or SMA) or other work-up (e.g. muscle biopsy) is reported for several subjects but was normal/non-diagnostic. All were investigated by WES/WGS which revealed biallelic NRCAM variants. Sanger sequencing was used for confirmation and segregation analyses, with compatible results in several affected/unaffected sibs tested. There were no alternative explanations for the NDD phenotype with the exception of one subject with a mosaic functionally characterized LP KRAS variant suspected to contribute to his phenotype. NRCAM encodes neuronal cell adhesion molecule (CAM). CAMs are membrane bound proteins with important role in tissue morphogenesis and maintenance. They mediate interactions between neighboring cells or cells and the extracellular matrix. The L1 subgroup of immunoglobulin CAMS - consisting of L1CAM, neurofascin, NRCAM, CHL1 - is the most abundant in the CNS with several critical functions in CNS development, among others in neural cell differentiation, axonal growth and guidance, myelination, synapse formation. Pathogenic L1CAM (XL) and NFASC variants (AR) are associated with NDD. Different missense (N=7), stopgain/frameshift (N=3), a splice variant (NM_001037132.2:c.2647-2A>G) as well as a deep intronic one (c.230+824G>C / rs575851831). Variants occurred in different domains with a cluster (42%) in the fibronectin III domain. Missense SNVs were ultrarare or not present in gnomAD, occurred in conserved residues, with several in silico predictions in favor of a deleterious effect. Structural modelling suggested that all substitutions occurred at residues exposed to solvent and possible abrogated interaction with other proteins. There were no expression studies performed at the mRNA/protein level. The splice variant is predicted to cause ex22 skipping leading to frameshift. The deep intronic variant is predicted to disrupt a site for spl. regulator SC35 and may cause activation of a cryptic acceptor site with inclusion of a cryptic exon. The zebrafish nrcama gene is the sole ortholog of human NRCAM, with another gene proposed as possible ortholog (nrcamb) mapping upon BLAST analysis to cntn1a. The authors performed CRISPR-Cas9 mutagenesis in zebrafish introducing a partial deletion of ex18 and 19. Mutant zebrafish were viable, displayed altered axonal projections and abnormal swimming behavior (increased movement in darkness). Currently, there is no NRCAM-associated phenotype in OMIM/G2P/SysID. PanelApp Australia includes NRCAM in its ID panel with green rating. Consider inclusion probably with green (>3 individuals/families/variants, segregation, gene in the L1-Ig CAM family causing NDD, zebrafish model) or amber rating (ID not a universal feature, variant effect not studied). Sources: Literature
13 Mar 2022	Early onset or syndromic epilepsy v2.498	TIAM1	Konstantinos Varvagiannis gene: TIAM1 was added gene: TIAM1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIAM1 were set to 35240055; 33328293 Phenotypes for gene: TIAM1 were set to Delayed speech and language development; Global developmental delay; Intellectual disability; Seizures; Behavioral abnormality; Abnormality of the endocrine system; Hypothyroidism; Abnormality of nervous system morphology Penetrance for gene: TIAM1 were set to Complete Review for gene: TIAM1 was set to AMBER Added comment: Lu et al (2022 - PMID: 35240055) describe 5 individuals (from 4 families) with biallelic TIAM1 missense variants. The phenotype overall corresponded to a neurodevelopmental disorder with DD (5/5), ID (4/4 individuals of relevant age - 3 families), speech delay (5/5), seizures (5/5 - onset: 2m-13y) and behavioral abnormalities (2/2, sibs with autism and ADHD). Several subjects had endocrine symptoms, namely hypothyroidism (N=3 - 2 families), Addison's disease (1) or hypomagnesemia (1). Non-consistent abnormalities were reported in (3/3) subjects who had a brain MRI. Previous investigations were mentioned for 3 individuals (incl. 2 sibs) and included normal CMA and/or metabolic workup. Singleton or trio exome sequencing (in one family) revealed biallelic missense TIAM1 variants. 6 different missense variants were reported, all ultra-rare or not present in gnomAD (also o/e:0.2, pLI:0.96), with CADD scores in favor of deleterious effect (NM_001353694.2): c.67C>T/p.Arg23Cys, c.2584C>T/p.Leu862Phe, c.983G>T/p.Gly328Val*, c.4640C>A/p.Ala1547Glu, c.1144G>C/p.Gly382Arg, c.4016C>T/p.Ala1339Val. TIAM1 encodes a RAC1-specific guanine exchange factor (GEF), regulating RAC1 signaling pathways that in turn affect cell shape, migration, adhesion, growth, survival, and polarity, and influence actin cytoskeletal organization, endocytosis, and membrane trafficking. RAC1 signaling plays important role in control of neuronal morphogenesis and neurite outgrowth (based on the summary by Entrez and authors). TIAM1 is highly expressed in human brain (GTEx). The authors provide evidence that sif, the Drosophila ortholog, is expressed primarily in neurons of the fly CNS (but not in glia). Using different sif LoF mutant flies they demonstrate that loss of sif impairs viability. Surviving flies exhibited climbing defects and seizure-like behaviors, both significantly rescued upon UAS-sif expression. Neuronal specific sif knockdown resulted in similar phenotypes to ubiquitous knockdown, while glial knockdown did not result in climbing defects. The semi-lethal phenotype could be fully rescued by expression of the fly sif cDNA, but only partially by human TIAM1 cDNA reference. Upon expression, 3 patient-variants (R23C, L862F, G328V) had variable rescue abilities similar to or lower (R23C) than TIAM1 Ref. TIAM1 Ref and variants could not rescue the neurological phenotypes though. Higher/ectopic expression of sif or TIAM1 Ref was toxic, which was also observed to a lesser extent for variants. Overall, the evidence provided suggests that the 3 variants tested induce partial LoF. In a recent study cited (PMID: 33328293), Tiam1 KO mice had simplified dendritic arbors, reduced spine density and diminished excitatory transmission in dentate gyrus. The authors comment that this mouse model presented only subtle behavioral abnormalities which they speculate may be secondary to GEF redundancy (eg. Tiam2). There is no TIAM1-associated phenotype in OMIM/G2P/SysID. TIAM1 is included in PanelApp Australia in the ID and epilepsy panels with green rating. Consider inclusion in the current panel with amber rating [As authors discuss: some phenotypic features differed in their small cohort and the contribution of other recessive conditions in 2 consanguineous families cannot be excluded. Also: in fig S1 only status of parents but not of affected/unaffected sibs is specified with the exception of Fam1]. Sources: Literature
13 Mar 2022	Intellectual disability v3.1518	TIAM1	Konstantinos Varvagiannis gene: TIAM1 was added gene: TIAM1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TIAM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIAM1 were set to 35240055; 33328293 Phenotypes for gene: TIAM1 were set to Delayed speech and language development; Global developmental delay; Intellectual disability; Seizures; Behavioral abnormality; Abnormality of the endocrine system; Hypothyroidism; Abnormality of nervous system morphology Penetrance for gene: TIAM1 were set to Complete Review for gene: TIAM1 was set to AMBER Added comment: Lu et al (2022 - PMID: 35240055) describe 5 individuals (from 4 families) with biallelic TIAM1 missense variants. The phenotype overall corresponded to a neurodevelopmental disorder with DD (5/5), ID (4/4 individuals of relevant age - 3 families), speech delay (5/5), seizures (5/5 - onset: 2m-13y) and behavioral abnormalities (2/2, sibs with autism and ADHD). Several subjects had endocrine symptoms, namely hypothyroidism (N=3 - 2 families), Addison's disease (1) or hypomagnesemia (1). Non-consistent abnormalities were reported in (3/3) subjects who had a brain MRI. Previous investigations were mentioned for 3 individuals (incl. 2 sibs) and included normal CMA and/or metabolic workup. Singleton or trio exome sequencing (in one family) revealed biallelic missense TIAM1 variants. 6 different missense variants were reported, all ultra-rare or not present in gnomAD (also o/e:0.2, pLI:0.96), with CADD scores in favor of deleterious effect (NM_001353694.2): c.67C>T/p.Arg23Cys, c.2584C>T/p.Leu862Phe, c.983G>T/p.Gly328Val*, c.4640C>A/p.Ala1547Glu, c.1144G>C/p.Gly382Arg, c.4016C>T/p.Ala1339Val. TIAM1 encodes a RAC1-specific guanine exchange factor (GEF), regulating RAC1 signaling pathways that in turn affect cell shape, migration, adhesion, growth, survival, and polarity, and influence actin cytoskeletal organization, endocytosis, and membrane trafficking. RAC1 signaling plays important role in control of neuronal morphogenesis and neurite outgrowth (based on the summary by Entrez and authors). TIAM1 is highly expressed in human brain (GTEx). The authors provide evidence that sif, the Drosophila ortholog, is expressed primarily in neurons of the fly CNS (but not in glia). Using different sif LoF mutant flies they demonstrate that loss of sif impairs viability. Surviving flies exhibited climbing defects and seizure-like behaviors, both significantly rescued upon UAS-sif expression. Neuronal specific sif knockdown resulted in similar phenotypes to ubiquitous knockdown, while glial knockdown did not result in climbing defects. The semi-lethal phenotype could be fully rescued by expression of the fly sif cDNA, but only partially by human TIAM1 cDNA reference. Upon expression, 3 patient-variants (R23C, L862F, G328V) had variable rescue abilities similar to or lower (R23C) than TIAM1 Ref. TIAM1 Ref and variants could not rescue the neurological phenotypes though. Higher/ectopic expression of sif or TIAM1 Ref was toxic, which was also observed to a lesser extent for variants. Overall, the evidence provided suggests that the 3 variants tested induce partial LoF. In a recent study cited (PMID: 33328293), Tiam1 KO mice had simplified dendritic arbors, reduced spine density and diminished excitatory transmission in dentate gyrus. The authors comment that this mouse model presented only subtle behavioral abnormalities which they speculate may be secondary to GEF redundancy (eg. Tiam2). There is no TIAM1-associated phenotype in OMIM/G2P/SysID. TIAM1 is included in PanelApp Australia in the ID and epilepsy panels with green rating. Consider inclusion in the current panel with amber rating [As authors discuss: some phenotypic features differed in their small cohort and the contribution of other recessive conditions in 2 consanguineous families cannot be excluded. Also: in fig S1 only status of parents but not of affected/unaffected sibs is specified with the exception of Fam1]. Sources: Literature
12 Mar 2022	Intellectual disability v3.1518	THUMPD1	Konstantinos Varvagiannis reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30237576, 35196516; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Hearing abnormality, Abnormality of the eye, Febrile seizures, Behavioral abnormality, Abnormality of brain morphology, Abnormality of the face; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
11 Mar 2022	Early onset or syndromic epilepsy v2.498	GABRD	Ivone Leong Tag Q4_21_rating was removed from gene: GABRD. Tag Q4_21_NHS_review was removed from gene: GABRD.
11 Mar 2022	Early onset or syndromic epilepsy v2.498	HPDL	Ivone Leong Tag Q2_21_rating was removed from gene: HPDL.
11 Mar 2022	Early onset or syndromic epilepsy v2.498	UFSP2	Ivone Leong Tag Q2_21_rating was removed from gene: UFSP2. Tag Q2_21_expert_review was removed from gene: UFSP2. Tag Q2_21_NHS_review was removed from gene: UFSP2.
11 Mar 2022	Early onset or syndromic epilepsy v2.498	UFSP2	Sarah Leigh commented on gene: UFSP2: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
11 Mar 2022	Early onset or syndromic epilepsy v2.498	HPDL	Sarah Leigh commented on gene: HPDL
11 Mar 2022	Early onset or syndromic epilepsy v2.498	GABRD	Sarah Leigh commented on gene: GABRD: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
11 Mar 2022	Early onset or syndromic epilepsy v2.498	UFSP2	Ivone Leong Source Expert Review Green was added to UFSP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Early onset or syndromic epilepsy v2.498	HPDL	Ivone Leong Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Early onset or syndromic epilepsy v2.498	GABRD	Ivone Leong Source Expert Review Green was added to GABRD. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	VPS41	Ivone Leong Tag Q2_21_rating was removed from gene: VPS41. Tag Q2_21_NHS_review was removed from gene: VPS41.
11 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.288	VPS41	Sarah Leigh commented on gene: VPS41
11 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.287	VPS41	Ivone Leong Source Expert Review Green was added to VPS41. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.154	EBP	Ivone Leong Tag Q2_21_expert_review was removed from gene: EBP.
11 Mar 2022	Arthrogryposis v3.154	ERBB3	Ivone Leong Tag Q2_21_rating was removed from gene: ERBB3.
11 Mar 2022	Arthrogryposis v3.154	ERGIC1	Ivone Leong Tag Q3_21_rating was removed from gene: ERGIC1.
11 Mar 2022	Arthrogryposis v3.154	FLNA	Ivone Leong Tag Q3_21_rating was removed from gene: FLNA.
11 Mar 2022	Arthrogryposis v3.154	KIDINS220	Ivone Leong Tag Q2_21_rating was removed from gene: KIDINS220.
11 Mar 2022	Arthrogryposis v3.154	MED12	Ivone Leong Tag Q3_21_rating was removed from gene: MED12.
11 Mar 2022	Arthrogryposis v3.154	MYLPF	Ivone Leong Tag Q2_21_expert_review was removed from gene: MYLPF.
11 Mar 2022	Arthrogryposis v3.154	SLC29A3	Ivone Leong Tag Q4_21_rating was removed from gene: SLC29A3. Tag Q4_21_NHS_review was removed from gene: SLC29A3.
11 Mar 2022	Arthrogryposis v3.154	SLC6A9	Ivone Leong Tag Q4_21_rating was removed from gene: SLC6A9. Tag Q4_21_NHS_review was removed from gene: SLC6A9.
11 Mar 2022	Arthrogryposis v3.154	SYNE1	Ivone Leong Tag Q2_21_rating was removed from gene: SYNE1.
11 Mar 2022	Arthrogryposis v3.154	MYL1	Ivone Leong Tag Q2_21_rating was removed from gene: MYL1.
11 Mar 2022	Arthrogryposis v3.154	FBN2	Ivone Leong Tag Q2_21_MOI was removed from gene: FBN2.
11 Mar 2022	Arthrogryposis v3.154	SYNE1	Sarah Leigh commented on gene: SYNE1
11 Mar 2022	Arthrogryposis v3.154	SLC6A9	Sarah Leigh commented on gene: SLC6A9
11 Mar 2022	Arthrogryposis v3.154	SLC29A3	Sarah Leigh commented on gene: SLC29A3
11 Mar 2022	Arthrogryposis v3.154	MYLPF	Sarah Leigh commented on gene: MYLPF
11 Mar 2022	Arthrogryposis v3.154	MYL1	Sarah Leigh commented on gene: MYL1
11 Mar 2022	Arthrogryposis v3.154	MED12	Sarah Leigh commented on gene: MED12
11 Mar 2022	Arthrogryposis v3.154	KIDINS220	Sarah Leigh commented on gene: KIDINS220
11 Mar 2022	Arthrogryposis v3.154	FLNA	Sarah Leigh commented on gene: FLNA
11 Mar 2022	Arthrogryposis v3.154	FBN2	Sarah Leigh commented on gene: FBN2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
11 Mar 2022	Arthrogryposis v3.154	ERGIC1	Sarah Leigh commented on gene: ERGIC1
11 Mar 2022	Arthrogryposis v3.154	ERBB3	Sarah Leigh commented on gene: ERBB3: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
11 Mar 2022	Arthrogryposis v3.154	EBP	Sarah Leigh commented on gene: EBP
11 Mar 2022	Arthrogryposis v3.153	SYNE1	Ivone Leong Source Expert Review Green was added to SYNE1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	SLC6A9	Ivone Leong Source Expert Review Green was added to SLC6A9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	SLC29A3	Ivone Leong Source Expert Review Green was added to SLC29A3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	MYL1	Ivone Leong Source Expert Review Red was added to MYL1. Rating Changed from Green List (high evidence) to Red List (low evidence)
11 Mar 2022	Arthrogryposis v3.153	MED12	Ivone Leong Source Expert Review Green was added to MED12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	KIDINS220	Ivone Leong Source Expert Review Green was added to KIDINS220. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	FLNA	Ivone Leong Source Expert Review Green was added to FLNA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	FBN2	Ivone Leong Source NHS GMS was added to FBN2. Mode of inheritance for gene FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
11 Mar 2022	Arthrogryposis v3.153	ERGIC1	Ivone Leong Source Expert Review Green was added to ERGIC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	ERBB3	Ivone Leong Source Expert Review Green was added to ERBB3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Arthrogryposis v3.153	EBP	Ivone Leong Source Expert Review Green was added to EBP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	PPP2R5D	Ivone Leong Tag Q2_21_phenotype was removed from gene: PPP2R5D.
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	VPS16	Ivone Leong Tag Q2_21_rating was removed from gene: VPS16. Tag Q2_21_NHS_review was removed from gene: VPS16.
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	VPS41	Ivone Leong Tag Q2_21_expert_review was removed from gene: VPS41. Tag Q2_21_NHS_review was removed from gene: VPS41.
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	VPS41	Sarah Leigh commented on gene: VPS41
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	VPS16	Sarah Leigh commented on gene: VPS16
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.166	PPP2R5D	Sarah Leigh commented on gene: PPP2R5D: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.165	VPS16	Ivone Leong Source Expert Review Green was added to VPS16. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.165	PPP2R5D	Ivone Leong Source Expert Review Green was added to PPP2R5D. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
11 Mar 2022	Cystic kidney disease v2.35	DZIP1L	Yu Leng Phua Deleted their comment
11 Mar 2022	Cystic kidney disease v2.35	DZIP1L	Yu Leng Phua edited their review of gene: DZIP1L: Added comment: Four children from three consanguineous families presenting with polycystic kidney disease; Variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp); Functional analyses of the c.216C > G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L; NOTE: Lack of liver phenotype in these patients; Changed phenotypes to: # 617610 POLYCYSTIC KIDNEY DISEASE 5, PKD5
11 Mar 2022	Cystic kidney disease v2.35	DZIP1L	Yu Leng Phua reviewed gene: DZIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 35211789; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
11 Mar 2022	Intellectual disability v3.1518	HEATR3	Konstantinos Varvagiannis gene: HEATR3 was added gene: HEATR3 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HEATR3 were set to 35213692 Phenotypes for gene: HEATR3 were set to Anemia; Thrombocytopenia; Growth delay; Short stature; Abnormality of the skeletal system; Abnormality of finger; Abnormality of the thumb; Intellectual disability; Obesity; Abnormality of the face Penetrance for gene: HEATR3 were set to Complete Review for gene: HEATR3 was set to AMBER Added comment: O'Donohue et al (2022 - PMID: 35213692) describe the clinical features of 6 individuals (from 4 unrelated families) with biallelic pathogenic HEATR3 variants. These included bone marrow failure (anemia/anemia and thrombocytopenia at presentation), short stature/growth retardation (4/6), facial features (5/6 - in some: straight eyebrows, d-s palpebral fissures, synophrys) and skeletal findings incl. disproportionately short fingers/thumb anomaly. ID was reported in 4/6 individuals from 3 families (all: mild ID \| 2/6 without ID). The phenotype corresponded overall to a variant form Diamond-Blackfan anemia (DBA, disorder caused by variants in genes encoding for ribosomal proteins) with additional features. The 1st family (2 affected sibs and parents) underwent WES, not diagnostic for DBA. Analysis suggested variants in HEATR3 (prioritized due to its potential role in ribosome biogenesis) and 4 additional genes as candidates. Collaboration in the European DBA consortium and national DBA consortia led to identification of additional families. HEATR3 encodes Heat-repeat-containing protein 3 or symportin, a protein that co-imports uL5 (encoded by RPL11) and uL18 (RPL5) in the nucleus where they assemble with 5S rRNA to form 5S RNP. The 5S RNP complex incorporates with maturing large ribosomal subunits to form the central protuberance. When 5S RNP is not incorporated, it accumulates and associates with Hdm2 ubiquitin ligase, the later normally targeting p53 proteasomal degradation. The following missense and splice variants were identified (NM_182922): - c.1751G>Α/p.(Gly584Glu) hmz - c.1337G>A/p.(Cys446Tyr) hmz - c.399+1G>T in trans with c.719C>T/p.(Pro240Leu) - c.400T>C/p.(Cys134Arg) hmz Variants were confirmed with Sanger sequencing. They were dispersed across HEATR3 without clustering although they affect residues either in the ARM (38-320) or HEAT (415-675) repeat domains, at positions evolutionary conserved, with in silico predictions in favor of a deleterious effect. With the exception of Cys134Arg (AF:4.11x10-6/no hmz), all were absent from gnomAD. Studies in yeast suggested that deletions in symportin gene (syo1) lead to a mild growth defect and accumulation of 40S subunits. Similarly, two yeast strains engineered to test for the effect of the p.Gly584Glu (yeast p.Gly522Glu/Ala) exhibited growth defect and ribosomal subunit imbalance, both restored by wt Syo1. HA-tagged HEATR3 in HeLa cells suggested that the co-translational capture mechanism to chaperone uL18 (RPL5) is conserved in human cells but was not observed upon expression of the p.Cys446Tyr variant. While HEATR3 transcription was not affected in LCLs from individuals hmz for Gly584Glu or Cys446Tyr, protein levels were barely detectable, suggesting destabilization of the protein. While uL18 accumulates in cytoplasm and nucleus with expected enrichment in nucleolus, upon siRNA knockdown of HEATR3 in HeLa cells this enrichment was lost. Studies in fibroblasts (Gly584Glu) demonstrated reduced uL18 nuclear staining. Overall, HEATR3 was suggested to be important for nuclear import of uL18 (though not for uL5). LCL studies demonstrated pre-rRNA processing defects in patient cells with accumulation of 32S and 12S pre-rRNAs, the former being reminiscent of accumulations observed in individuals with RPL5- and RPL11-related DBA. Expression of wt HEATR3 restored processing defects. LCLs from affected individuals revealed loss of free 60S subunits (as in yeast) with expression of wt cDNA restoring Nl levels. Western blots of LCLs demonstrated that the levels of uL5, uL18 and p53 were not affected (the latter also observed in RPL5-related DBA) Studies of bone marrow smears from 2 affected individuals allowed to conclude in a strong defect in erythroid cell proliferation. Currently, there is no HEATR3-associated phenotype in OMIM, PanelApp Australia, G2P or the SysID database. Consider inclusion in the ID panel with amber (mild ID in >3 individuals/families/variants although not universal feature) or green rating. Also consider inclusion in other possibly relevant panels eg. for cytopenias/congenital anemias, short stature, etc. Sources: Literature
10 Mar 2022	Adult onset neurodegenerative disorder v2.267	HTT_CAG	Arina Puzriakova Classified STR: HTT_CAG as Green List (high evidence)
10 Mar 2022	Adult onset neurodegenerative disorder v2.267	HTT_CAG	Arina Puzriakova Str: htt_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	HTT_CAG	Arina Puzriakova Classified STR: HTT_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.105	HTT_CAG	Arina Puzriakova Str: htt_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.289	HTT_CAG	Arina Puzriakova Classified STR: HTT_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.289	HTT_CAG	Arina Puzriakova Str: htt_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.298	HTT_CAG	Arina Puzriakova Classified STR: HTT_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.298	HTT_CAG	Arina Puzriakova Str: htt_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	HTT_CAG	Arina Puzriakova Classified STR: HTT_CAG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.76	HTT_CAG	Arina Puzriakova Str: htt_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.104	TBP_CAG	Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.104	TBP_CAG	Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.288	TBP_CAG	Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.288	TBP_CAG	Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.297	TBP_CAG	Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.297	TBP_CAG	Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.75	TBP_CAG	Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.75	TBP_CAG	Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
10 Mar 2022	Brain channelopathy v1.77	TBP_CAG	Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
10 Mar 2022	Brain channelopathy v1.77	TBP_CAG	Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.103	PPP2R2B_CAG	Arina Puzriakova Classified STR: PPP2R2B_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.103	PPP2R2B_CAG	Arina Puzriakova Str: ppp2r2b_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.287	PPP2R2B_CAG	Arina Puzriakova Classified STR: PPP2R2B_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.287	PPP2R2B_CAG	Arina Puzriakova Str: ppp2r2b_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.296	PPP2R2B_CAG	Arina Puzriakova Classified STR: PPP2R2B_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.296	PPP2R2B_CAG	Arina Puzriakova Str: ppp2r2b_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.295	NOP56_GGCCTG	Arina Puzriakova Classified STR: NOP56_GGCCTG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.295	NOP56_GGCCTG	Arina Puzriakova Str: nop56_ggcctg has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.74	NOP56_GGCCTG	Arina Puzriakova Classified STR: NOP56_GGCCTG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.74	NOP56_GGCCTG	Arina Puzriakova Str: nop56_ggcctg has been classified as Green List (High Evidence).
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	NOP56_GGCCTG	Arina Puzriakova Classified STR: NOP56_GGCCTG as Green List (high evidence)
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.56	NOP56_GGCCTG	Arina Puzriakova Str: nop56_ggcctg has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.102	JPH3_CTG	Arina Puzriakova Classified STR: JPH3_CTG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.102	JPH3_CTG	Arina Puzriakova Str: jph3_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dystonia v1.111	JPH3_CTG	Arina Puzriakova Classified STR: JPH3_CTG as Green List (high evidence)
10 Mar 2022	Early onset dystonia v1.111	JPH3_CTG	Arina Puzriakova Str: jph3_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Intellectual disability v3.1518	FMR1_CGG	Arina Puzriakova Classified STR: FMR1_CGG as Green List (high evidence)
10 Mar 2022	Intellectual disability v3.1518	FMR1_CGG	Arina Puzriakova Str: fmr1_cgg has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.73	JPH3_CTG	Arina Puzriakova Classified STR: JPH3_CTG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.73	JPH3_CTG	Arina Puzriakova Str: jph3_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.286	FXN_GAA	Arina Puzriakova Classified STR: FXN_GAA as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.286	FXN_GAA	Arina Puzriakova Str: fxn_gaa has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary neuropathy v1.441	FXN_GAA	Arina Puzriakova Classified STR: FXN_GAA as Green List (high evidence)
10 Mar 2022	Hereditary neuropathy v1.441	FXN_GAA	Arina Puzriakova Str: fxn_gaa has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.294	FXN_GAA	Arina Puzriakova Classified STR: FXN_GAA as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.294	FXN_GAA	Arina Puzriakova Str: fxn_gaa has been classified as Green List (High Evidence).
10 Mar 2022	Intellectual disability v3.1518	DMPK_CTG	Arina Puzriakova Classified STR: DMPK_CTG as Green List (high evidence)
10 Mar 2022	Intellectual disability v3.1518	DMPK_CTG	Arina Puzriakova Str: dmpk_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Mitochondrial disorders v2.92	DMPK_CTG	Arina Puzriakova Classified STR: DMPK_CTG as Green List (high evidence)
10 Mar 2022	Mitochondrial disorders v2.92	DMPK_CTG	Arina Puzriakova Str: dmpk_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Skeletal Muscle Channelopathies v1.45	DMPK_CTG	Arina Puzriakova Classified STR: DMPK_CTG as Green List (high evidence)
10 Mar 2022	Skeletal Muscle Channelopathies v1.45	DMPK_CTG	Arina Puzriakova Str: dmpk_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Congenital myopathy v2.79	DMPK_CTG	Arina Puzriakova Classified STR: DMPK_CTG as Green List (high evidence)
10 Mar 2022	Congenital myopathy v2.79	DMPK_CTG	Arina Puzriakova Str: dmpk_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Congenital muscular dystrophy v2.27	DMPK_CTG	Arina Puzriakova Classified STR: DMPK_CTG as Green List (high evidence)
10 Mar 2022	Congenital muscular dystrophy v2.27	DMPK_CTG	Arina Puzriakova Str: dmpk_ctg has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.293	CSTB_CCCCGCCCCGCG	Arina Puzriakova Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.293	CSTB_CCCCGCCCCGCG	Arina Puzriakova Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
10 Mar 2022	Early onset or syndromic epilepsy v2.497	CSTB_CCCCGCCCCGCG	Arina Puzriakova Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
10 Mar 2022	Early onset or syndromic epilepsy v2.497	CSTB_CCCCGCCCCGCG	Arina Puzriakova Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
10 Mar 2022	Brain channelopathy v1.76	CSTB_CCCCGCCCCGCG	Arina Puzriakova Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
10 Mar 2022	Brain channelopathy v1.76	CSTB_CCCCGCCCCGCG	Arina Puzriakova Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.285	CACNA1A_CAG	Arina Puzriakova Classified STR: CACNA1A_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.285	CACNA1A_CAG	Arina Puzriakova Str: cacna1a_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.292	CACNA1A_CAG	Arina Puzriakova Classified STR: CACNA1A_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.292	CACNA1A_CAG	Arina Puzriakova Str: cacna1a_cag has been classified as Green List (High Evidence).
10 Mar 2022	Brain channelopathy v1.75	CACNA1A_CAG	Arina Puzriakova Classified STR: CACNA1A_CAG as Green List (high evidence)
10 Mar 2022	Brain channelopathy v1.75	CACNA1A_CAG	Arina Puzriakova Str: cacna1a_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.101	C9orf72_GGGGCC	Arina Puzriakova Classified STR: C9orf72_GGGGCC as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.101	C9orf72_GGGGCC	Arina Puzriakova Str: c9orf72_ggggcc has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.72	C9orf72_GGGGCC	Arina Puzriakova Classified STR: C9orf72_GGGGCC as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.72	C9orf72_GGGGCC	Arina Puzriakova Str: c9orf72_ggggcc has been classified as Green List (High Evidence).
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.55	C9orf72_GGGGCC	Arina Puzriakova Classified STR: C9orf72_GGGGCC as Green List (high evidence)
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.55	C9orf72_GGGGCC	Arina Puzriakova Str: c9orf72_ggggcc has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.284	ATXN7_CAG	Arina Puzriakova Classified STR: ATXN7_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.284	ATXN7_CAG	Arina Puzriakova Str: atxn7_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.291	ATXN7_CAG	Arina Puzriakova Classified STR: ATXN7_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.291	ATXN7_CAG	Arina Puzriakova Str: atxn7_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.100	ATXN3_CAG	Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.100	ATXN3_CAG	Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.283	ATXN3_CAG	Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.283	ATXN3_CAG	Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary neuropathy v1.440	ATXN3_CAG	Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
10 Mar 2022	Hereditary neuropathy v1.440	ATXN3_CAG	Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.290	ATXN3_CAG	Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.290	ATXN3_CAG	Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dystonia v1.110	ATXN3_CAG	Arina Puzriakova Classified STR: ATXN3_CAG as Green List (high evidence)
10 Mar 2022	Early onset dystonia v1.110	ATXN3_CAG	Arina Puzriakova Str: atxn3_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.99	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.99	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.282	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.282	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary neuropathy v1.439	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Hereditary neuropathy v1.439	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.289	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.289	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dystonia v1.109	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Early onset dystonia v1.109	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.71	ATXN2_CAG	Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.71	ATXN2_CAG	Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.281	ATXN10_ATTCT	Arina Puzriakova Classified STR: ATXN10_ATTCT as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.281	ATXN10_ATTCT	Arina Puzriakova Str: atxn10_attct has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary neuropathy v1.438	ATXN10_ATTCT	Arina Puzriakova Classified STR: ATXN10_ATTCT as Green List (high evidence)
10 Mar 2022	Hereditary neuropathy v1.438	ATXN10_ATTCT	Arina Puzriakova Str: atxn10_attct has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.288	ATXN10_ATTCT	Arina Puzriakova Classified STR: ATXN10_ATTCT as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.288	ATXN10_ATTCT	Arina Puzriakova Str: atxn10_attct has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.70	ATXN10_ATTCT	Arina Puzriakova Classified STR: ATXN10_ATTCT as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.70	ATXN10_ATTCT	Arina Puzriakova Str: atxn10_attct has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.98	ATXN1_CAG	Arina Puzriakova Classified STR: ATXN1_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.98	ATXN1_CAG	Arina Puzriakova Str: atxn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary spastic paraplegia v1.280	ATXN1_CAG	Arina Puzriakova Classified STR: ATXN1_CAG as Green List (high evidence)
10 Mar 2022	Hereditary spastic paraplegia v1.280	ATXN1_CAG	Arina Puzriakova Str: atxn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary neuropathy v1.437	ATXN1_CAG	Arina Puzriakova Classified STR: ATXN1_CAG as Green List (high evidence)
10 Mar 2022	Hereditary neuropathy v1.437	ATXN1_CAG	Arina Puzriakova Str: atxn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.287	ATXN1_CAG	Arina Puzriakova Classified STR: ATXN1_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.287	ATXN1_CAG	Arina Puzriakova Str: atxn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.69	ATXN1_CAG	Arina Puzriakova Classified STR: ATXN1_CAG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.69	ATXN1_CAG	Arina Puzriakova Str: atxn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.97	ATN1_CAG	Arina Puzriakova Classified STR: ATN1_CAG as Green List (high evidence)
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.97	ATN1_CAG	Arina Puzriakova Str: atn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Hereditary ataxia v1.286	ATN1_CAG	Arina Puzriakova Classified STR: ATN1_CAG as Green List (high evidence)
10 Mar 2022	Hereditary ataxia v1.286	ATN1_CAG	Arina Puzriakova Str: atn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset or syndromic epilepsy v2.496	ATN1_CAG	Arina Puzriakova Classified STR: ATN1_CAG as Green List (high evidence)
10 Mar 2022	Early onset or syndromic epilepsy v2.496	ATN1_CAG	Arina Puzriakova Str: atn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.68	ATN1_CAG	Arina Puzriakova Classified STR: ATN1_CAG as Green List (high evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.68	ATN1_CAG	Arina Puzriakova Str: atn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Brain channelopathy v1.74	ATN1_CAG	Arina Puzriakova Classified STR: ATN1_CAG as Green List (high evidence)
10 Mar 2022	Brain channelopathy v1.74	ATN1_CAG	Arina Puzriakova Str: atn1_cag has been classified as Green List (High Evidence).
10 Mar 2022	Distal myopathies v1.45	AR_CAG	Arina Puzriakova Classified STR: AR_CAG as Green List (high evidence)
10 Mar 2022	Distal myopathies v1.45	AR_CAG	Arina Puzriakova Str: ar_cag has been classified as Green List (High Evidence).
10 Mar 2022	Congenital myopathy v2.78	AR_CAG	Arina Puzriakova Classified STR: AR_CAG as Green List (high evidence)
10 Mar 2022	Congenital myopathy v2.78	AR_CAG	Arina Puzriakova Str: ar_cag has been classified as Green List (High Evidence).
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.54	AR_CAG	Arina Puzriakova Classified STR: AR_CAG as Green List (high evidence)
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.54	AR_CAG	Arina Puzriakova Str: ar_cag has been classified as Green List (High Evidence).
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source Expert Review Removed was added to STR: HTT_CAG. Rating Changed from Green List (high evidence) to No List (delete)
10 Mar 2022	Structural basal ganglia disorders v1.28	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36.
10 Mar 2022	Hereditary spastic paraplegia v1.277	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36.
10 Mar 2022	Hereditary ataxia v1.283	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Brain channelopathy v1.71	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG.
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36. Source NHS GMS was added to STR: HTT_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	HTT_CAG	Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36.
10 Mar 2022	Paroxysmal central nervous system disorders v1.38	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
10 Mar 2022	Hereditary spastic paraplegia v1.277	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia v1.283	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.213	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
10 Mar 2022	Brain channelopathy v1.71	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	TBP_CAG	Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Intellectual disability v3.1515	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
10 Mar 2022	Hereditary spastic paraplegia v1.277	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG.
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
10 Mar 2022	Hereditary ataxia v1.283	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43. Source NHS GMS was added to STR: PPP2R2B_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	PPP2R2B_CAG	Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33. Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
10 Mar 2022	Hereditary neuropathy v1.434	NOP56_GGCCTG	Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG.
10 Mar 2022	Hereditary ataxia v1.283	NOP56_GGCCTG	Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	NOP56_GGCCTG	Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	NOP56_GGCCTG	Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG.
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.51	NOP56_GGCCTG	Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	JPH3_CTG	Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	JPH3_CTG	Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40. Source NHS GMS was added to STR: JPH3_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dystonia v1.106	JPH3_CTG	Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40. Source NHS GMS was added to STR: JPH3_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	JPH3_CTG	Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40. Source NHS GMS was added to STR: JPH3_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	JPH3_CTG	Arina Puzriakova Pathogenic Number of Repeats for JPH3_CTG was changed from 41 to 40.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Mitochondrial disorders v2.89	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Intellectual disability v3.1515	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Hypertrophic cardiomyopathy v2.36	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Hereditary spastic paraplegia v1.277	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia v1.283	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Likely inborn error of metabolism v2.226	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.213	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	FXN_GAA	Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
10 Mar 2022	Primary ovarian insufficiency v1.65	FMR1_CGG	Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG.
10 Mar 2022	Intellectual disability v3.1515	FMR1_CGG	Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	FMR1_CGG	Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG.
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	FMR1_CGG	Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG.
10 Mar 2022	Hereditary ataxia v1.283	FMR1_CGG	Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG.
10 Mar 2022	Skeletal muscle channelopathy v1.37	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Paroxysmal central nervous system disorders v1.38	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Skeletal Muscle Channelopathies v1.42	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Mitochondrial disorders v2.89	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Paediatric motor neuronopathies v1.74	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Intellectual disability v3.1515	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Gastrointestinal neuromuscular disorders v1.19	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source Expert Review Red was added to STR: DMPK_CTG. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Fetal hydrops v1.48	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source Expert Review Red was added to STR: DMPK_CTG. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Fetal anomalies v1.840	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Likely inborn error of metabolism v2.226	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	DDG2P v2.63	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG.
10 Mar 2022	Congenital myopathy v2.75	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Congenital muscular dystrophy v2.24	DMPK_CTG	Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35. Source NHS GMS was added to STR: DMPK_CTG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Paroxysmal central nervous system disorders v1.38	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
10 Mar 2022	Intellectual disability v3.1515	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18.
10 Mar 2022	Hereditary ataxia v1.283	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset or syndromic epilepsy v2.493	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.213	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
10 Mar 2022	Brain channelopathy v1.71	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18. Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	CSTB_CCCCGCCCCGCG	Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18.
10 Mar 2022	Skeletal muscle channelopathy v1.37	CNBP_CCTG	Arina Puzriakova Normal Number of Repeats for CNBP_CCTG was changed from 26 to 27. Source NHS GMS was added to STR: CNBP_CCTG.
10 Mar 2022	Skeletal Muscle Channelopathies v1.42	CNBP_CCTG	Arina Puzriakova Normal Number of Repeats for CNBP_CCTG was changed from 26 to 27. Source Expert Review Red was added to STR: CNBP_CCTG. Source NHS GMS was added to STR: CNBP_CCTG.
10 Mar 2022	Fetal anomalies v1.840	CNBP_CCTG	Arina Puzriakova Normal Number of Repeats for CNBP_CCTG was changed from 26 to 27. Source NHS GMS was added to STR: CNBP_CCTG.
10 Mar 2022	Distal myopathies v1.42	CNBP_CCTG	Arina Puzriakova Normal Number of Repeats for CNBP_CCTG was changed from 26 to 27. Source Expert Review Red was added to STR: CNBP_CCTG. Source NHS GMS was added to STR: CNBP_CCTG.
10 Mar 2022	Paroxysmal central nervous system disorders v1.38	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19.
10 Mar 2022	Hereditary spastic paraplegia v1.277	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19.
10 Mar 2022	Hereditary ataxia v1.283	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Brain channelopathy v1.71	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19. Source NHS GMS was added to STR: CACNA1A_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	CACNA1A_CAG	Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200. Source NHS GMS was added to STR: C9orf72_GGGGCC. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Intellectual disability v3.1515	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200. Source NHS GMS was added to STR: C9orf72_GGGGCC.
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200. Source NHS GMS was added to STR: C9orf72_GGGGCC. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.213	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200.
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.51	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200. Source NHS GMS was added to STR: C9orf72_GGGGCC. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	C9orf72_GGGGCC	Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24. Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37.
10 Mar 2022	Undiagnosed metabolic disorders v1.511	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG.
10 Mar 2022	Intellectual disability v3.1515	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37.
10 Mar 2022	Hereditary spastic paraplegia v1.277	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG.
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37.
10 Mar 2022	Hereditary ataxia v1.283	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATXN7_CAG	Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28. Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37. Source NHS GMS was added to STR: ATXN7_CAG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Intellectual disability v3.1515	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
10 Mar 2022	Hereditary spastic paraplegia v1.277	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
10 Mar 2022	Hereditary ataxia v1.283	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dystonia v1.106	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN3_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	ATXN3_CAG	Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Intellectual disability v3.1515	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
10 Mar 2022	Hereditary spastic paraplegia v1.277	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
10 Mar 2022	Hereditary ataxia v1.283	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dystonia v1.106	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Childhood onset dystonia, chorea or related movement disorder v1.213	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG.
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG.
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.51	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35. Source NHS GMS was added to STR: ATXN2_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	ATXN2_CAG	Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32. Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
10 Mar 2022	Thoracic dystrophies v1.16	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Skeletal dysplasia v2.187	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
10 Mar 2022	Intellectual disability v3.1515	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
10 Mar 2022	Hereditary spastic paraplegia v1.277	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
10 Mar 2022	Hereditary ataxia v1.283	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dystonia v1.106	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATXN10_ATTCT	Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33. Source NHS GMS was added to STR: ATXN10_ATTCT.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Intellectual disability v3.1515	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG.
10 Mar 2022	Childhood onset hereditary spastic paraplegia v2.126	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG.
10 Mar 2022	Adult onset hereditary spastic paraplegia v1.91	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
10 Mar 2022	Hereditary spastic paraplegia v1.277	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary neuropathy v1.434	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
10 Mar 2022	Hereditary ataxia v1.283	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45. Source NHS GMS was added to STR: ATXN1_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	ATXN1_CAG	Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36. Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
10 Mar 2022	Paroxysmal central nervous system disorders v1.38	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36.
10 Mar 2022	Parkinson Disease and Complex Parkinsonism v1.94	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Hereditary ataxia with onset in adulthood v2.145	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36.
10 Mar 2022	Hereditary ataxia v1.283	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset or syndromic epilepsy v2.493	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.65	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Brain channelopathy v1.71	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Ataxia and cerebellar anomalies - narrow panel v2.284	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36. Source NHS GMS was added to STR: ATN1_CAG.
10 Mar 2022	Adult onset dystonia, chorea or related movement disorder v1.162	ATN1_CAG	Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36.
10 Mar 2022	Adult onset neurodegenerative disorder v2.264	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35.
10 Mar 2022	Paediatric motor neuronopathies v1.74	AR_CAG	Arina Puzriakova GRCh37 position for AR_CAG was changed from - to 66765160-66765225. Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG.
10 Mar 2022	Hereditary neuropathy or pain disorder v1.84	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG.
10 Mar 2022	Hereditary neuropathy v1.434	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG.
10 Mar 2022	Distal myopathies v1.42	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Congenital myopathy v2.75	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Amyotrophic lateral sclerosis/motor neuron disease v1.51	AR_CAG	Arina Puzriakova Normal Number of Repeats for AR_CAG was changed from 34 to 35. Source NHS GMS was added to STR: AR_CAG. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Adult onset neurodegenerative disorder v2.263	SORL1	Eleanor Williams Tag Q3_21_NHS_review was removed from gene: SORL1.
10 Mar 2022	Adult onset neurodegenerative disorder v2.263	FIG4	Eleanor Williams Tag Q3_21_NHS_review was removed from gene: FIG4. Tag Q4_21_expert_review was removed from gene: FIG4.
10 Mar 2022	Adult onset neurodegenerative disorder v2.263	ERBB4	Eleanor Williams Tag Q2_21_rating was removed from gene: ERBB4.
10 Mar 2022	Adult onset neurodegenerative disorder v2.263	FIG4	Sarah Leigh commented on gene: FIG4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Adult onset neurodegenerative disorder v2.263	ERBB4	Sarah Leigh commented on gene: ERBB4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Adult onset neurodegenerative disorder v2.262	FIG4	Eleanor Williams Source Expert Review Red was added to FIG4. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Adult onset neurodegenerative disorder v2.262	ERBB4	Eleanor Williams Source Expert Review Green was added to ERBB4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Fetal anomalies v1.839	ISCA-46302-Gain	Arina Puzriakova Tag for-review was removed from Region: ISCA-46302-Gain.
10 Mar 2022	Differences in sex development v2.58	ISCA-46302-Gain	Arina Puzriakova Tag for-review was removed from Region: ISCA-46302-Gain.
10 Mar 2022	Differences in sex development v2.58	ISCA-46302-Gain	Arina Puzriakova Classified Region: ISCA-46302-Gain as Green List (high evidence)
10 Mar 2022	Differences in sex development v2.58	ISCA-46302-Gain	Arina Puzriakova Region: isca-46302-gain has been classified as Green List (High Evidence).
10 Mar 2022	Differences in sex development v2.57	ISCA-46302-Gain	Arina Puzriakova commented on Region: ISCA-46302-Gain
10 Mar 2022	Fetal anomalies v1.839	ISCA-46302-Gain	Arina Puzriakova commented on Region: ISCA-46302-Gain
10 Mar 2022	Fetal anomalies v1.839	ISCA-46302-Gain	Arina Puzriakova Haploinsufficiency Score for ISCA-46302-Gain was changed from None to . Source Expert Review Green was added to Region: ISCA-46302-Gain. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.96	NADSYN1	Arina Puzriakova Tag for-review was removed from gene: NADSYN1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	MYOCD	Arina Puzriakova Tag for-review was removed from gene: MYOCD.
10 Mar 2022	Paediatric disorders - additional genes v1.96	LRIG2	Arina Puzriakova Tag for-review was removed from gene: LRIG2.
10 Mar 2022	Paediatric disorders - additional genes v1.96	ITGA8	Arina Puzriakova Tag for-review was removed from gene: ITGA8.
10 Mar 2022	Paediatric disorders - additional genes v1.96	GREB1L	Arina Puzriakova Tag for-review was removed from gene: GREB1L.
10 Mar 2022	Paediatric disorders - additional genes v1.96	GATA3	Arina Puzriakova Tag for-review was removed from gene: GATA3.
10 Mar 2022	Paediatric disorders - additional genes v1.96	CHRNA3	Arina Puzriakova Tag for-review was removed from gene: CHRNA3.
10 Mar 2022	Paediatric disorders - additional genes v1.96	ANOS1	Arina Puzriakova Tag for-review was removed from gene: ANOS1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	AGT	Arina Puzriakova Tag for-review was removed from gene: AGT.
10 Mar 2022	Paediatric disorders - additional genes v1.96	AGTR1	Arina Puzriakova Tag for-review was removed from gene: AGTR1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	ACE	Arina Puzriakova Tag for-review was removed from gene: ACE.
10 Mar 2022	Paediatric disorders - additional genes v1.96	ACTG2	Arina Puzriakova Tag for-review was removed from gene: ACTG2.
10 Mar 2022	Paediatric disorders - additional genes v1.96	TBX18	Arina Puzriakova Tag for-review was removed from gene: TBX18.
10 Mar 2022	Paediatric disorders - additional genes v1.96	REN	Arina Puzriakova Tag for-review was removed from gene: REN.
10 Mar 2022	Paediatric disorders - additional genes v1.96	TSPYL1	Arina Puzriakova Tag for-review was removed from gene: TSPYL1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	STN1	Arina Puzriakova Tag for-review was removed from gene: STN1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	PIGQ	Arina Puzriakova Tag for-review was removed from gene: PIGQ.
10 Mar 2022	Paediatric disorders - additional genes v1.96	CDH2	Arina Puzriakova Tag for-review was removed from gene: CDH2.
10 Mar 2022	Paediatric disorders - additional genes v1.96	RINT1	Arina Puzriakova Tag for-review was removed from gene: RINT1.
10 Mar 2022	Paediatric disorders - additional genes v1.96	HYAL2	Arina Puzriakova Tag for-review was removed from gene: HYAL2.
10 Mar 2022	Paediatric disorders - additional genes v1.96	NADSYN1	Sarah Leigh commented on gene: NADSYN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Paediatric disorders - additional genes v1.96	MYOCD	Sarah Leigh commented on gene: MYOCD: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Paediatric disorders - additional genes v1.96	LRIG2	Sarah Leigh commented on gene: LRIG2
10 Mar 2022	Paediatric disorders - additional genes v1.96	ITGA8	Sarah Leigh commented on gene: ITGA8
10 Mar 2022	Paediatric disorders - additional genes v1.96	GREB1L	Sarah Leigh commented on gene: GREB1L
10 Mar 2022	Paediatric disorders - additional genes v1.96	GATA3	Sarah Leigh commented on gene: GATA3
10 Mar 2022	Paediatric disorders - additional genes v1.96	CHRNA3	Sarah Leigh commented on gene: CHRNA3
10 Mar 2022	Paediatric disorders - additional genes v1.96	ANOS1	Sarah Leigh commented on gene: ANOS1
10 Mar 2022	Paediatric disorders - additional genes v1.96	AGTR1	Sarah Leigh commented on gene: AGTR1
10 Mar 2022	Paediatric disorders - additional genes v1.96	AGT	Sarah Leigh commented on gene: AGT
10 Mar 2022	Paediatric disorders - additional genes v1.96	ACE	Sarah Leigh commented on gene: ACE
10 Mar 2022	Paediatric disorders - additional genes v1.96	ACTG2	Sarah Leigh commented on gene: ACTG2
10 Mar 2022	Paediatric disorders - additional genes v1.96	TBX18	Sarah Leigh commented on gene: TBX18
10 Mar 2022	Paediatric disorders - additional genes v1.96	REN	Sarah Leigh commented on gene: REN
10 Mar 2022	Paediatric disorders - additional genes v1.96	TSPYL1	Sarah Leigh commented on gene: TSPYL1
10 Mar 2022	Paediatric disorders - additional genes v1.96	STN1	Sarah Leigh commented on gene: STN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Paediatric disorders - additional genes v1.96	PIGQ	Sarah Leigh commented on gene: PIGQ: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Paediatric disorders - additional genes v1.96	CDH2	Sarah Leigh commented on gene: CDH2
10 Mar 2022	Paediatric disorders - additional genes v1.96	RINT1	Sarah Leigh commented on gene: RINT1
10 Mar 2022	Paediatric disorders - additional genes v1.96	HYAL2	Sarah Leigh commented on gene: HYAL2
10 Mar 2022	Paediatric disorders - additional genes v1.95	NADSYN1	Arina Puzriakova Source Expert Review Green was added to NADSYN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	MYOCD	Arina Puzriakova Source Expert Review Green was added to MYOCD. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	LRIG2	Arina Puzriakova Source Expert Review Green was added to LRIG2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	ITGA8	Arina Puzriakova Source Expert Review Green was added to ITGA8. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	GREB1L	Arina Puzriakova Source Expert Review Green was added to GREB1L. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	GATA3	Arina Puzriakova Source Expert Review Green was added to GATA3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	CHRNA3	Arina Puzriakova Source Expert Review Green was added to CHRNA3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	ANOS1	Arina Puzriakova Source Expert Review Green was added to ANOS1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	AGTR1	Arina Puzriakova Source Expert Review Green was added to AGTR1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	AGT	Arina Puzriakova Source Expert Review Green was added to AGT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	ACE	Arina Puzriakova Source Expert Review Green was added to ACE. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	ACTG2	Arina Puzriakova Source Expert Review Green was added to ACTG2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	TBX18	Arina Puzriakova Source Expert Review Green was added to TBX18. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	REN	Arina Puzriakova Source Expert Review Green was added to REN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	TSPYL1	Arina Puzriakova Source Expert Review Green was added to TSPYL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	STN1	Arina Puzriakova Source Expert Review Green was added to STN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	PIGQ	Arina Puzriakova Source Expert Review Green was added to PIGQ. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	CDH2	Arina Puzriakova Source Expert Review Green was added to CDH2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	RINT1	Arina Puzriakova Source Expert Review Green was added to RINT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Paediatric disorders - additional genes v1.95	HYAL2	Arina Puzriakova Source Expert Review Green was added to HYAL2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.293	CEP63	Eleanor Williams Tag Q2_21_expert_review was removed from gene: CEP63.
10 Mar 2022	Severe microcephaly v2.293	YIPF5	Eleanor Williams Tag Q2_21_rating was removed from gene: YIPF5.
10 Mar 2022	Severe microcephaly v2.293	WDR4	Eleanor Williams Tag Q2_21_rating was removed from gene: WDR4.
10 Mar 2022	Severe microcephaly v2.293	WDR37	Eleanor Williams Tag Q2_21_rating was removed from gene: WDR37.
10 Mar 2022	Severe microcephaly v2.293	WDR11	Eleanor Williams Tag Q4_21_rating was removed from gene: WDR11.
10 Mar 2022	Severe microcephaly v2.293	VRK1	Eleanor Williams Tag Q3_21_rating was removed from gene: VRK1.
10 Mar 2022	Severe microcephaly v2.293	UNC80	Eleanor Williams Tag Q2_21_rating was removed from gene: UNC80.
10 Mar 2022	Severe microcephaly v2.293	UGP2	Eleanor Williams Tag Q2_21_rating was removed from gene: UGP2.
10 Mar 2022	Severe microcephaly v2.293	TSEN54	Eleanor Williams Tag Q2_21_rating was removed from gene: TSEN54.
10 Mar 2022	Severe microcephaly v2.293	TSEN15	Eleanor Williams Tag Q2_21_rating was removed from gene: TSEN15.
10 Mar 2022	Severe microcephaly v2.293	TRIO	Eleanor Williams Tag Q2_21_rating was removed from gene: TRIO.
10 Mar 2022	Severe microcephaly v2.293	TRAPPC9	Eleanor Williams Tag Q2_21_rating was removed from gene: TRAPPC9.
10 Mar 2022	Severe microcephaly v2.293	TRAPPC6B	Eleanor Williams Tag Q2_21_rating was removed from gene: TRAPPC6B.
10 Mar 2022	Severe microcephaly v2.293	TP53RK	Eleanor Williams Tag Q2_21_rating was removed from gene: TP53RK.
10 Mar 2022	Severe microcephaly v2.293	TNPO2	Eleanor Williams Tag Q3_21_rating was removed from gene: TNPO2.
10 Mar 2022	Severe microcephaly v2.293	SMARCA5	Eleanor Williams Tag Q2_21_rating was removed from gene: SMARCA5.
10 Mar 2022	Severe microcephaly v2.293	SLC1A4	Eleanor Williams Tag Q2_21_rating was removed from gene: SLC1A4.
10 Mar 2022	Severe microcephaly v2.293	RAD51	Eleanor Williams Tag Q4_21_rating was removed from gene: RAD51.
10 Mar 2022	Severe microcephaly v2.293	RAD50	Eleanor Williams Tag Q2_21_rating was removed from gene: RAD50.
10 Mar 2022	Severe microcephaly v2.293	PUS7	Eleanor Williams Tag Q2_21_rating was removed from gene: PUS7.
10 Mar 2022	Severe microcephaly v2.293	PUF60	Eleanor Williams Tag Q2_21_rating was removed from gene: PUF60.
10 Mar 2022	Severe microcephaly v2.293	PTPN23	Eleanor Williams Tag Q2_21_rating was removed from gene: PTPN23.
10 Mar 2022	Severe microcephaly v2.293	POGZ	Eleanor Williams Tag Q2_21_rating was removed from gene: POGZ.
10 Mar 2022	Severe microcephaly v2.293	PCDH12	Eleanor Williams Tag Q3_21_rating was removed from gene: PCDH12.
10 Mar 2022	Severe microcephaly v2.293	OSGEP	Eleanor Williams Tag Q3_21_rating was removed from gene: OSGEP.
10 Mar 2022	Severe microcephaly v2.293	NUP107	Eleanor Williams Tag Q3_21_rating was removed from gene: NUP107.
10 Mar 2022	Severe microcephaly v2.293	MINPP1	Eleanor Williams Tag Q2_21_rating was removed from gene: MINPP1.
10 Mar 2022	Severe microcephaly v2.293	LAGE3	Eleanor Williams Tag Q3_21_rating was removed from gene: LAGE3.
10 Mar 2022	Severe microcephaly v2.293	HPDL	Eleanor Williams Tag Q2_21_rating was removed from gene: HPDL.
10 Mar 2022	Severe microcephaly v2.293	HIST1H4C	Eleanor Williams Tag Q3_21_rating was removed from gene: HIST1H4C.
10 Mar 2022	Severe microcephaly v2.293	GTF2E2	Eleanor Williams Tag Q3_21_rating was removed from gene: GTF2E2.
10 Mar 2022	Severe microcephaly v2.293	GPT2	Eleanor Williams Tag Q4_21_rating was removed from gene: GPT2.
10 Mar 2022	Severe microcephaly v2.293	FOXG1	Eleanor Williams Tag Q2_21_rating was removed from gene: FOXG1.
10 Mar 2022	Severe microcephaly v2.293	EIF5A	Eleanor Williams Tag Q2_21_rating was removed from gene: EIF5A.
10 Mar 2022	Severe microcephaly v2.293	EIF2S3	Eleanor Williams Tag Q3_21_rating was removed from gene: EIF2S3.
10 Mar 2022	Severe microcephaly v2.293	DYNC1I2	Eleanor Williams Tag Q4_21_rating was removed from gene: DYNC1I2.
10 Mar 2022	Severe microcephaly v2.293	DPM1	Eleanor Williams Tag Q2_21_rating was removed from gene: DPM1.
10 Mar 2022	Severe microcephaly v2.293	DNA2	Eleanor Williams Tag Q2_21_rating was removed from gene: DNA2.
10 Mar 2022	Severe microcephaly v2.293	CTU2	Eleanor Williams Tag Q2_21_rating was removed from gene: CTU2.
10 Mar 2022	Severe microcephaly v2.293	CTCF	Eleanor Williams Tag Q2_21_rating was removed from gene: CTCF.
10 Mar 2022	Severe microcephaly v2.293	CSNK2A1	Eleanor Williams Tag Q2_21_rating was removed from gene: CSNK2A1.
10 Mar 2022	Severe microcephaly v2.293	CHAMP1	Eleanor Williams Tag Q2_21_rating was removed from gene: CHAMP1.
10 Mar 2022	Severe microcephaly v2.293	CEP63	Eleanor Williams Phenotypes for gene: CEP63 were changed from MCPH; primary microcephaly; ?Seckel syndrome 6, 614728; Microcephaly to MCPH; primary microcephaly; ?Seckel syndrome 6, OMIM:614728; Microcephaly
10 Mar 2022	Severe microcephaly v2.292	CEP57	Eleanor Williams Tag Q2_21_rating was removed from gene: CEP57.
10 Mar 2022	Severe microcephaly v2.292	CAMK2B	Eleanor Williams Tag Q2_21_rating was removed from gene: CAMK2B.
10 Mar 2022	Severe microcephaly v2.292	BUB1B	Eleanor Williams Tag Q2_21_rating was removed from gene: BUB1B.
10 Mar 2022	Severe microcephaly v2.292	BPTF	Eleanor Williams Tag Q2_21_rating was removed from gene: BPTF.
10 Mar 2022	Severe microcephaly v2.292	AARS	Eleanor Williams Tag Q2_21_rating was removed from gene: AARS.
10 Mar 2022	Severe microcephaly v2.292	YIPF5	Sarah Leigh commented on gene: YIPF5
10 Mar 2022	Severe microcephaly v2.292	WDR4	Sarah Leigh commented on gene: WDR4
10 Mar 2022	Severe microcephaly v2.292	WDR37	Sarah Leigh commented on gene: WDR37
10 Mar 2022	Severe microcephaly v2.292	WDR11	Sarah Leigh commented on gene: WDR11
10 Mar 2022	Severe microcephaly v2.292	VRK1	Sarah Leigh commented on gene: VRK1
10 Mar 2022	Severe microcephaly v2.292	UNC80	Sarah Leigh commented on gene: UNC80
10 Mar 2022	Severe microcephaly v2.292	UGP2	Sarah Leigh commented on gene: UGP2
10 Mar 2022	Severe microcephaly v2.292	TSEN54	Sarah Leigh commented on gene: TSEN54
10 Mar 2022	Severe microcephaly v2.292	TSEN15	Sarah Leigh commented on gene: TSEN15
10 Mar 2022	Severe microcephaly v2.292	TRIO	Sarah Leigh commented on gene: TRIO
10 Mar 2022	Severe microcephaly v2.292	TRAPPC9	Sarah Leigh commented on gene: TRAPPC9
10 Mar 2022	Severe microcephaly v2.292	TRAPPC6B	Sarah Leigh commented on gene: TRAPPC6B
10 Mar 2022	Severe microcephaly v2.292	TP53RK	Sarah Leigh commented on gene: TP53RK
10 Mar 2022	Severe microcephaly v2.292	TNPO2	Sarah Leigh commented on gene: TNPO2
10 Mar 2022	Severe microcephaly v2.292	SMARCA5	Sarah Leigh commented on gene: SMARCA5
10 Mar 2022	Severe microcephaly v2.292	SLC1A4	Sarah Leigh commented on gene: SLC1A4
10 Mar 2022	Severe microcephaly v2.292	RAD51	Sarah Leigh commented on gene: RAD51
10 Mar 2022	Severe microcephaly v2.292	RAD50	Sarah Leigh commented on gene: RAD50
10 Mar 2022	Severe microcephaly v2.292	PUS7	Sarah Leigh commented on gene: PUS7
10 Mar 2022	Severe microcephaly v2.292	PUF60	Sarah Leigh commented on gene: PUF60
10 Mar 2022	Severe microcephaly v2.292	PTPN23	Sarah Leigh commented on gene: PTPN23
10 Mar 2022	Severe microcephaly v2.292	POGZ	Sarah Leigh commented on gene: POGZ
10 Mar 2022	Severe microcephaly v2.292	PCDH12	Sarah Leigh commented on gene: PCDH12
10 Mar 2022	Severe microcephaly v2.292	OSGEP	Sarah Leigh commented on gene: OSGEP
10 Mar 2022	Severe microcephaly v2.292	NUP107	Sarah Leigh commented on gene: NUP107
10 Mar 2022	Severe microcephaly v2.292	MINPP1	Sarah Leigh commented on gene: MINPP1
10 Mar 2022	Severe microcephaly v2.292	LAGE3	Sarah Leigh commented on gene: LAGE3
10 Mar 2022	Severe microcephaly v2.292	HPDL	Sarah Leigh commented on gene: HPDL
10 Mar 2022	Severe microcephaly v2.292	HIST1H4C	Sarah Leigh commented on gene: HIST1H4C
10 Mar 2022	Severe microcephaly v2.292	GTF2E2	Sarah Leigh commented on gene: GTF2E2
10 Mar 2022	Severe microcephaly v2.292	GPT2	Sarah Leigh commented on gene: GPT2
10 Mar 2022	Severe microcephaly v2.292	FOXG1	Sarah Leigh commented on gene: FOXG1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.292	EIF5A	Sarah Leigh commented on gene: EIF5A
10 Mar 2022	Severe microcephaly v2.292	EIF2S3	Sarah Leigh commented on gene: EIF2S3
10 Mar 2022	Severe microcephaly v2.292	DYNC1I2	Sarah Leigh commented on gene: DYNC1I2
10 Mar 2022	Severe microcephaly v2.292	DPM1	Sarah Leigh commented on gene: DPM1
10 Mar 2022	Severe microcephaly v2.292	DNA2	Sarah Leigh commented on gene: DNA2
10 Mar 2022	Severe microcephaly v2.292	CTU2	Sarah Leigh commented on gene: CTU2
10 Mar 2022	Severe microcephaly v2.292	CTCF	Sarah Leigh commented on gene: CTCF
10 Mar 2022	Severe microcephaly v2.292	CSNK2A1	Sarah Leigh commented on gene: CSNK2A1
10 Mar 2022	Severe microcephaly v2.292	CHAMP1	Sarah Leigh commented on gene: CHAMP1
10 Mar 2022	Severe microcephaly v2.292	CEP63	Sarah Leigh commented on gene: CEP63
10 Mar 2022	Severe microcephaly v2.292	CEP57	Sarah Leigh commented on gene: CEP57
10 Mar 2022	Severe microcephaly v2.292	CAMK2B	Sarah Leigh commented on gene: CAMK2B
10 Mar 2022	Severe microcephaly v2.292	BUB1B	Sarah Leigh commented on gene: BUB1B
10 Mar 2022	Severe microcephaly v2.292	BPTF	Sarah Leigh commented on gene: BPTF
10 Mar 2022	Severe microcephaly v2.292	AARS	Sarah Leigh commented on gene: AARS
10 Mar 2022	Severe microcephaly v2.291	YIPF5	Eleanor Williams Source Expert Review Green was added to YIPF5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	WDR4	Eleanor Williams Source Expert Review Green was added to WDR4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	WDR37	Eleanor Williams Source Expert Review Green was added to WDR37. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	WDR11	Eleanor Williams Source Expert Review Green was added to WDR11. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	VRK1	Eleanor Williams Source Expert Review Green was added to VRK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	UNC80	Eleanor Williams Source Expert Review Green was added to UNC80. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	UGP2	Eleanor Williams Source Expert Review Green was added to UGP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TSEN54	Eleanor Williams Source Expert Review Green was added to TSEN54. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TSEN15	Eleanor Williams Source Expert Review Green was added to TSEN15. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TRIO	Eleanor Williams Source Expert Review Green was added to TRIO. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TRAPPC9	Eleanor Williams Source Expert Review Green was added to TRAPPC9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TRAPPC6B	Eleanor Williams Source Expert Review Green was added to TRAPPC6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TP53RK	Eleanor Williams Source Expert Review Green was added to TP53RK. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	TNPO2	Eleanor Williams Source Expert Review Green was added to TNPO2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	SMARCA5	Eleanor Williams Source Expert Review Green was added to SMARCA5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	SLC1A4	Eleanor Williams Source Expert Review Green was added to SLC1A4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	RAD51	Eleanor Williams Source Expert Review Green was added to RAD51. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	RAD50	Eleanor Williams Source Expert Review Green was added to RAD50. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	PUS7	Eleanor Williams Source Expert Review Green was added to PUS7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	PUF60	Eleanor Williams Source Expert Review Green was added to PUF60. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	PTPN23	Eleanor Williams Source Expert Review Green was added to PTPN23. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	POGZ	Eleanor Williams Source Expert Review Green was added to POGZ. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	PCDH12	Eleanor Williams Source Expert Review Green was added to PCDH12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	OSGEP	Eleanor Williams Source Expert Review Green was added to OSGEP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	NUP107	Eleanor Williams Source Expert Review Green was added to NUP107. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	MINPP1	Eleanor Williams Source Expert Review Green was added to MINPP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	LAGE3	Eleanor Williams Source Expert Review Green was added to LAGE3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	HPDL	Eleanor Williams Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	HIST1H4C	Eleanor Williams Source Expert Review Green was added to HIST1H4C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	GTF2E2	Eleanor Williams Source Expert Review Green was added to GTF2E2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	GPT2	Eleanor Williams Source Expert Review Green was added to GPT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	FOXG1	Eleanor Williams Source Expert Review Green was added to FOXG1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	EIF5A	Eleanor Williams Source Expert Review Green was added to EIF5A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	EIF2S3	Eleanor Williams Source Expert Review Green was added to EIF2S3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	DYNC1I2	Eleanor Williams Source Expert Review Green was added to DYNC1I2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	DPM1	Eleanor Williams Source Expert Review Green was added to DPM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	DNA2	Eleanor Williams Source Expert Review Green was added to DNA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CTU2	Eleanor Williams Source Expert Review Green was added to CTU2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CTCF	Eleanor Williams Source Expert Review Green was added to CTCF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CSNK2A1	Eleanor Williams Source Expert Review Green was added to CSNK2A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CHAMP1	Eleanor Williams Source Expert Review Green was added to CHAMP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CEP63	Eleanor Williams Source Expert Review Red was added to CEP63. Rating Changed from Green List (high evidence) to Red List (low evidence)
10 Mar 2022	Severe microcephaly v2.291	CEP57	Eleanor Williams Source Expert Review Green was added to CEP57. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	CAMK2B	Eleanor Williams Source Expert Review Green was added to CAMK2B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	BUB1B	Eleanor Williams Source Expert Review Green was added to BUB1B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	BPTF	Eleanor Williams Source Expert Review Green was added to BPTF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.291	AARS	Eleanor Williams Source Expert Review Green was added to AARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.290	METTL5	Eleanor Williams Phenotypes for gene: METTL5 were changed from Intellectual developmental disorder, autosomal recessive 72, 618665 to Intellectual developmental disorder, autosomal recessive 72, OMIM:618665
10 Mar 2022	Severe microcephaly v2.289	METTL5	Eleanor Williams Tag for-review was removed from gene: METTL5.
10 Mar 2022	Severe microcephaly v2.289	AP4S1	Eleanor Williams Publications for gene: AP4S1 were set to 21620353; 25552650; 27444738
10 Mar 2022	Severe microcephaly v2.288	AP4S1	Eleanor Williams Tag for-review was removed from gene: AP4S1.
10 Mar 2022	Severe microcephaly v2.288	AP4M1	Eleanor Williams Tag for-review was removed from gene: AP4M1. Tag missense tag was added to gene: AP4M1.
10 Mar 2022	Severe microcephaly v2.288	AP4B1	Eleanor Williams Tag for-review was removed from gene: AP4B1.
10 Mar 2022	Severe microcephaly v2.288	UBE3A	Eleanor Williams Phenotypes for gene: UBE3A were changed from Angelman syndrome 105830 to Angelman syndrome, OMIM:105830
10 Mar 2022	Severe microcephaly v2.287	UBE3A	Eleanor Williams Tag for-review was removed from gene: UBE3A.
10 Mar 2022	Severe microcephaly v2.287	ZNF526	Eleanor Williams Tag for-review was removed from gene: ZNF526.
10 Mar 2022	Severe microcephaly v2.287	SMG8	Eleanor Williams Tag for-review was removed from gene: SMG8.
10 Mar 2022	Intellectual disability v3.1514	EXT2	Arina Puzriakova Tag for-review was removed from gene: EXT2.
10 Mar 2022	Intellectual disability v3.1514	CTNND1	Arina Puzriakova Tag for-review was removed from gene: CTNND1.
10 Mar 2022	Intellectual disability v3.1514	SLC12A6	Arina Puzriakova commented on gene: SLC12A6
10 Mar 2022	Intellectual disability v3.1514	SLC12A6	Arina Puzriakova Tag for-review was removed from gene: SLC12A6.
10 Mar 2022	Intellectual disability v3.1514	SCN8A	Arina Puzriakova Tag for-review was removed from gene: SCN8A.
10 Mar 2022	Intellectual disability v3.1514	CDK19	Arina Puzriakova Tag for-review was removed from gene: CDK19.
10 Mar 2022	Intellectual disability v3.1514	ABCA2	Arina Puzriakova Tag for-review was removed from gene: ABCA2.
10 Mar 2022	Intellectual disability v3.1514	PIGH	Arina Puzriakova Tag for-review was removed from gene: PIGH.
10 Mar 2022	Intellectual disability v3.1514	METTL5	Arina Puzriakova Tag for-review was removed from gene: METTL5.
10 Mar 2022	Intellectual disability v3.1514	LMBRD2	Arina Puzriakova Tag for-review was removed from gene: LMBRD2.
10 Mar 2022	Intellectual disability v3.1514	LIAS	Arina Puzriakova Tag for-review was removed from gene: LIAS.
10 Mar 2022	Intellectual disability v3.1514	CSNK1G1	Arina Puzriakova Tag for-review was removed from gene: CSNK1G1.
10 Mar 2022	Intellectual disability v3.1514	ALG14	Arina Puzriakova Tag for-review was removed from gene: ALG14.
10 Mar 2022	Intellectual disability v3.1514	AGO2	Arina Puzriakova Tag for-review was removed from gene: AGO2.
10 Mar 2022	Intellectual disability v3.1514	PNPT1	Arina Puzriakova Tag for-review was removed from gene: PNPT1.
10 Mar 2022	Intellectual disability v3.1514	SCO1	Arina Puzriakova Tag for-review was removed from gene: SCO1.
10 Mar 2022	Intellectual disability v3.1514	FA2H	Arina Puzriakova Tag for-review was removed from gene: FA2H.
10 Mar 2022	Intellectual disability v3.1514	COX6B1	Arina Puzriakova Tag for-review was removed from gene: COX6B1.
10 Mar 2022	Intellectual disability v3.1514	MPI	Arina Puzriakova Tag for-review was removed from gene: MPI.
10 Mar 2022	Intellectual disability v3.1514	VAMP1	Arina Puzriakova Tag watchlist was removed from gene: VAMP1. Tag for-review was removed from gene: VAMP1.
10 Mar 2022	Intellectual disability v3.1514	TRIM32	Arina Puzriakova Tag for-review was removed from gene: TRIM32.
10 Mar 2022	Intellectual disability v3.1514	MGP	Arina Puzriakova Tag for-review was removed from gene: MGP.
10 Mar 2022	Intellectual disability v3.1514	LGI4	Arina Puzriakova Tag for-review was removed from gene: LGI4.
10 Mar 2022	Intellectual disability v3.1514	HYLS1	Arina Puzriakova Tag for-review was removed from gene: HYLS1.
10 Mar 2022	Intellectual disability v3.1514	HADH	Arina Puzriakova Tag for-review was removed from gene: HADH.
10 Mar 2022	Intellectual disability v3.1514	FLVCR1	Arina Puzriakova Tag for-review was removed from gene: FLVCR1.
10 Mar 2022	Intellectual disability v3.1514	ATL1	Arina Puzriakova Tag for-review was removed from gene: ATL1.
10 Mar 2022	Intellectual disability v3.1514	ANKH	Arina Puzriakova Tag for-review was removed from gene: ANKH.
10 Mar 2022	Intellectual disability v3.1514	AFG3L2	Arina Puzriakova Mode of inheritance for gene: AFG3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
10 Mar 2022	Intellectual disability v3.1513	AFG3L2	Arina Puzriakova Tag for-review was removed from gene: AFG3L2. Tag Q2_21_MOI was removed from gene: AFG3L2.
10 Mar 2022	Intellectual disability v3.1513	KCNC3	Arina Puzriakova Tag for-review was removed from gene: KCNC3.
10 Mar 2022	Intellectual disability v3.1513	ALKBH8	Arina Puzriakova Tag for-review was removed from gene: ALKBH8.
10 Mar 2022	Intellectual disability v3.1513	SOX3	Arina Puzriakova Tag for-review was removed from gene: SOX3.
10 Mar 2022	Intellectual disability v3.1513	PRKD1	Arina Puzriakova Tag for-review was removed from gene: PRKD1.
10 Mar 2022	Intellectual disability v3.1513	GPSM2	Arina Puzriakova Tag for-review was removed from gene: GPSM2.
10 Mar 2022	Intellectual disability v3.1513	DDOST	Arina Puzriakova Tag for-review was removed from gene: DDOST.
10 Mar 2022	Intellectual disability v3.1513	CYP2U1	Arina Puzriakova Tag for-review was removed from gene: CYP2U1.
10 Mar 2022	Intellectual disability v3.1513	AGPS	Arina Puzriakova Tag for-review was removed from gene: AGPS.
10 Mar 2022	Intellectual disability v3.1513	TMEM106B	Arina Puzriakova Tag for-review was removed from gene: TMEM106B.
10 Mar 2022	Intellectual disability v3.1513	NEMF	Arina Puzriakova Tag for-review was removed from gene: NEMF.
10 Mar 2022	Intellectual disability v3.1513	MPP5	Arina Puzriakova Tag for-review was removed from gene: MPP5.
10 Mar 2022	Intellectual disability v3.1513	MAPK1	Arina Puzriakova Tag for-review was removed from gene: MAPK1.
10 Mar 2022	Intellectual disability v3.1513	LMNB1	Arina Puzriakova Tag for-review was removed from gene: LMNB1.
10 Mar 2022	Intellectual disability v3.1513	KIF21B	Arina Puzriakova Tag for-review was removed from gene: KIF21B.
10 Mar 2022	Intellectual disability v3.1513	JARID2	Arina Puzriakova Tag for-review was removed from gene: JARID2.
10 Mar 2022	Intellectual disability v3.1513	FAM50A	Arina Puzriakova Tag for-review was removed from gene: FAM50A.
10 Mar 2022	Intellectual disability v3.1513	CEP120	Arina Puzriakova Tag for-review was removed from gene: CEP120.
10 Mar 2022	Intellectual disability v3.1513	ZNF526	Arina Puzriakova Tag for-review was removed from gene: ZNF526.
10 Mar 2022	Intellectual disability v3.1513	TFE3	Arina Puzriakova Tag for-review was removed from gene: TFE3.
10 Mar 2022	Intellectual disability v3.1513	PIGQ	Arina Puzriakova Tag for-review was removed from gene: PIGQ.
10 Mar 2022	Intellectual disability v3.1513	KAT5	Arina Puzriakova Tag for-review was removed from gene: KAT5.
10 Mar 2022	Intellectual disability v3.1513	ZNF335	Arina Puzriakova Tag for-review was removed from gene: ZNF335.
10 Mar 2022	Intellectual disability v3.1513	ZIC1	Arina Puzriakova Tag for-review was removed from gene: ZIC1.
10 Mar 2022	Intellectual disability v3.1513	SETD1A	Arina Puzriakova Tag for-review was removed from gene: SETD1A.
10 Mar 2022	Intellectual disability v3.1513	PET100	Arina Puzriakova Tag for-review was removed from gene: PET100.
10 Mar 2022	Intellectual disability v3.1513	NUDT2	Arina Puzriakova Tag for-review was removed from gene: NUDT2.
10 Mar 2022	Intellectual disability v3.1513	MFSD2A	Arina Puzriakova Tag for-review was removed from gene: MFSD2A.
10 Mar 2022	Severe microcephaly v2.287	NARS	Eleanor Williams Tag for-review was removed from gene: NARS.
10 Mar 2022	Intellectual disability v3.1513	MAPRE2	Arina Puzriakova Tag for-review was removed from gene: MAPRE2.
10 Mar 2022	Severe microcephaly v2.287	MORC2	Eleanor Williams Tag for-review was removed from gene: MORC2.
10 Mar 2022	Severe microcephaly v2.287	LMNB2	Eleanor Williams Tag for-review was removed from gene: LMNB2.
10 Mar 2022	Intellectual disability v3.1513	CDH2	Arina Puzriakova Tag for-review was removed from gene: CDH2.
10 Mar 2022	Severe microcephaly v2.287	LMNB1	Eleanor Williams Tag for-review was removed from gene: LMNB1.
10 Mar 2022	Intellectual disability v3.1513	SMG8	Arina Puzriakova Tag for-review was removed from gene: SMG8.
10 Mar 2022	Intellectual disability v3.1513	LSS	Arina Puzriakova Tag watchlist was removed from gene: LSS. Tag for-review was removed from gene: LSS.
10 Mar 2022	Intellectual disability v3.1513	KCNMA1	Arina Puzriakova Tag for-review was removed from gene: KCNMA1.
10 Mar 2022	Intellectual disability v3.1513	H3F3B	Arina Puzriakova Tag for-review was removed from gene: H3F3B.
10 Mar 2022	Intellectual disability v3.1513	H3F3A	Arina Puzriakova Tag for-review was removed from gene: H3F3A.
10 Mar 2022	Intellectual disability v3.1513	KDM4B	Arina Puzriakova Tag for-review was removed from gene: KDM4B.
10 Mar 2022	Intellectual disability v3.1513	BICRA	Arina Puzriakova Tag for-review was removed from gene: BICRA.
10 Mar 2022	Intellectual disability v3.1513	ZFHX4	Arina Puzriakova Tag for-review was removed from gene: ZFHX4.
10 Mar 2022	Intellectual disability v3.1513	SHMT2	Arina Puzriakova Tag for-review was removed from gene: SHMT2.
10 Mar 2022	Intellectual disability v3.1513	NARS	Arina Puzriakova Tag for-review was removed from gene: NARS.
10 Mar 2022	Intellectual disability v3.1513	MORC2	Arina Puzriakova Tag for-review was removed from gene: MORC2.
10 Mar 2022	Intellectual disability v3.1513	LARS	Arina Puzriakova Tag for-review was removed from gene: LARS.
10 Mar 2022	Intellectual disability v3.1513	POLR1C	Arina Puzriakova Tag for-review was removed from gene: POLR1C.
10 Mar 2022	Intellectual disability v3.1513	NUS1	Arina Puzriakova Tag for-review was removed from gene: NUS1.
10 Mar 2022	Intellectual disability v3.1513	NUS1	Arina Puzriakova Phenotypes for gene: NUS1 were changed from #617082 - ?Congenital disorder of glycosylation, type 1aa; #617831 - Mental retardation, autosomal dominant 55, with seizures; Abnormality of extrapyramidal motor function to Mental retardation, autosomal dominant 55, with seizures, OMIM:617831; Congenital disorder of glycosylation, type 1aa, OMIM:617082
10 Mar 2022	Early onset or syndromic epilepsy v2.492	NUS1	Arina Puzriakova Phenotypes for gene: NUS1 were changed from ?Congenital disorder of glycosylation, type 1aa OMIM:617082; Mental retardation, autosomal dominant 55, with seizures OMIM:617831; Abnormality of extrapyramidal motor function to Mental retardation, autosomal dominant 55, with seizures, OMIM:617831; Congenital disorder of glycosylation, type 1aa, OMIM:617082
10 Mar 2022	Intellectual disability v3.1512	NUS1	Arina Puzriakova Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
10 Mar 2022	Intellectual disability v3.1511	PUM1	Arina Puzriakova Tag for-review was removed from gene: PUM1.
10 Mar 2022	Intellectual disability v3.1511	RALGAPA1	Arina Puzriakova Tag for-review was removed from gene: RALGAPA1.
10 Mar 2022	Intellectual disability v3.1511	RARS	Arina Puzriakova Tag for-review was removed from gene: RARS.
10 Mar 2022	Intellectual disability v3.1511	CEP55	Arina Puzriakova Tag for-review was removed from gene: CEP55.
10 Mar 2022	Intellectual disability v3.1511	CTU2	Arina Puzriakova Tag for-review was removed from gene: CTU2.
10 Mar 2022	Intellectual disability v3.1511	TRAPPC4	Arina Puzriakova Tag for-review was removed from gene: TRAPPC4.
10 Mar 2022	Intellectual disability v3.1511	UGP2	Arina Puzriakova Tag for-review was removed from gene: UGP2.
10 Mar 2022	Intellectual disability v3.1511	CXorf56	Arina Puzriakova Tag for-review was removed from gene: CXorf56.
10 Mar 2022	Intellectual disability v3.1511	KAT8	Arina Puzriakova Tag for-review was removed from gene: KAT8.
10 Mar 2022	Intellectual disability v3.1511	SLC5A6	Arina Puzriakova Tag for-review was removed from gene: SLC5A6.
10 Mar 2022	Intellectual disability v3.1511	SNX27	Arina Puzriakova Tag for-review was removed from gene: SNX27.
10 Mar 2022	Intellectual disability v3.1511	WNT1	Arina Puzriakova Tag for-review was removed from gene: WNT1.
10 Mar 2022	Intellectual disability v3.1511	YIF1B	Arina Puzriakova Tag for-review was removed from gene: YIF1B.
10 Mar 2022	Intellectual disability v3.1511	VARS2	Arina Puzriakova Tag for-review was removed from gene: VARS2.
10 Mar 2022	Intellectual disability v3.1511	UGDH	Arina Puzriakova Tag for-review was removed from gene: UGDH.
10 Mar 2022	Intellectual disability v3.1511	TTC5	Arina Puzriakova Tag for-review was removed from gene: TTC5.
10 Mar 2022	Intellectual disability v3.1511	TRNT1	Arina Puzriakova Tag for-review was removed from gene: TRNT1.
10 Mar 2022	Intellectual disability v3.1511	TNRC6B	Arina Puzriakova Tag for-review was removed from gene: TNRC6B.
10 Mar 2022	Intellectual disability v3.1511	TET3	Arina Puzriakova Tag for-review was removed from gene: TET3.
10 Mar 2022	Intellectual disability v3.1511	TENM3	Arina Puzriakova Tag for-review was removed from gene: TENM3.
10 Mar 2022	Intellectual disability v3.1511	TASP1	Arina Puzriakova Tag for-review was removed from gene: TASP1.
10 Mar 2022	Intellectual disability v3.1511	SUZ12	Arina Puzriakova Tag for-review was removed from gene: SUZ12.
10 Mar 2022	Intellectual disability v3.1511	SUPT16H	Arina Puzriakova Tag for-review was removed from gene: SUPT16H.
10 Mar 2022	Intellectual disability v3.1511	SPTBN4	Arina Puzriakova Tag for-review was removed from gene: SPTBN4.
10 Mar 2022	Intellectual disability v3.1511	SPOP	Arina Puzriakova Tag for-review was removed from gene: SPOP.
10 Mar 2022	Intellectual disability v3.1511	SOX6	Arina Puzriakova Tag for-review was removed from gene: SOX6.
10 Mar 2022	Intellectual disability v3.1511	SLC1A1	Arina Puzriakova Tag for-review was removed from gene: SLC1A1.
10 Mar 2022	Intellectual disability v3.1511	SLC12A2	Arina Puzriakova Tag for-review was removed from gene: SLC12A2.
10 Mar 2022	Intellectual disability v3.1511	SFXN4	Arina Puzriakova Tag for-review was removed from gene: SFXN4.
10 Mar 2022	Intellectual disability v3.1511	SBF1	Arina Puzriakova Tag for-review was removed from gene: SBF1.
10 Mar 2022	Intellectual disability v3.1511	SARS2	Arina Puzriakova Tag for-review was removed from gene: SARS2.
10 Mar 2022	Intellectual disability v3.1511	RSRC1	Arina Puzriakova Tag for-review was removed from gene: RSRC1.
10 Mar 2022	Intellectual disability v3.1511	PPP1R12A	Arina Puzriakova Tag for-review was removed from gene: PPP1R12A.
10 Mar 2022	Intellectual disability v3.1511	PIGS	Arina Puzriakova Tag for-review was removed from gene: PIGS.
10 Mar 2022	Intellectual disability v3.1511	PIGK	Arina Puzriakova Tag for-review was removed from gene: PIGK.
10 Mar 2022	Intellectual disability v3.1511	PIBF1	Arina Puzriakova Tag for-review was removed from gene: PIBF1.
10 Mar 2022	Intellectual disability v3.1511	PDHB	Arina Puzriakova Tag for-review was removed from gene: PDHB.
10 Mar 2022	Intellectual disability v3.1511	OXR1	Arina Puzriakova Tag for-review was removed from gene: OXR1.
10 Mar 2022	Intellectual disability v3.1511	NRROS	Arina Puzriakova Tag for-review was removed from gene: NRROS.
10 Mar 2022	Intellectual disability v3.1511	NOVA2	Arina Puzriakova Tag for-review was removed from gene: NOVA2.
10 Mar 2022	Intellectual disability v3.1511	NDUFA2	Arina Puzriakova Tag for-review was removed from gene: NDUFA2.
10 Mar 2022	Intellectual disability v3.1511	MTHFS	Arina Puzriakova Tag for-review was removed from gene: MTHFS.
10 Mar 2022	Intellectual disability v3.1511	MN1	Arina Puzriakova Tag for-review was removed from gene: MN1.
10 Mar 2022	Intellectual disability v3.1511	LYRM7	Arina Puzriakova Tag for-review was removed from gene: LYRM7.
10 Mar 2022	Intellectual disability v3.1511	LIPT1	Arina Puzriakova Tag for-review was removed from gene: LIPT1.
10 Mar 2022	Intellectual disability v3.1511	KLF7	Arina Puzriakova Tag for-review was removed from gene: KLF7.
10 Mar 2022	Intellectual disability v3.1511	KCNN3	Arina Puzriakova Tag for-review was removed from gene: KCNN3.
10 Mar 2022	Intellectual disability v3.1511	HNRNPH1	Arina Puzriakova Tag for-review was removed from gene: HNRNPH1.
10 Mar 2022	Intellectual disability v3.1511	GPC4	Arina Puzriakova Tag for-review was removed from gene: GPC4.
10 Mar 2022	Intellectual disability v3.1511	GALNT2	Arina Puzriakova Tag for-review was removed from gene: GALNT2.
10 Mar 2022	Intellectual disability v3.1511	EIF2AK2	Arina Puzriakova Tag for-review was removed from gene: EIF2AK2.
10 Mar 2022	Intellectual disability v3.1511	EARS2	Arina Puzriakova Tag for-review was removed from gene: EARS2.
10 Mar 2022	Intellectual disability v3.1511	DNM1L	Arina Puzriakova Tag for-review was removed from gene: DNM1L.
10 Mar 2022	Intellectual disability v3.1511	DHX37	Arina Puzriakova Tag for-review was removed from gene: DHX37.
10 Mar 2022	Intellectual disability v3.1511	CNTNAP1	Arina Puzriakova Tag for-review was removed from gene: CNTNAP1.
10 Mar 2022	Intellectual disability v3.1511	B9D2	Arina Puzriakova Tag for-review was removed from gene: B9D2.
10 Mar 2022	Intellectual disability v3.1511	ATAD1	Arina Puzriakova Tag for-review was removed from gene: ATAD1.
10 Mar 2022	Intellectual disability v3.1511	ADD3	Arina Puzriakova Tag for-review was removed from gene: ADD3.
10 Mar 2022	Intellectual disability v3.1511	ADARB1	Arina Puzriakova Tag for-review was removed from gene: ADARB1.
10 Mar 2022	Intellectual disability v3.1511	DLL1	Arina Puzriakova Tag for-review was removed from gene: DLL1.
10 Mar 2022	Severe microcephaly v2.287	DNMT3A	Eleanor Williams Tag for-review was removed from gene: DNMT3A.
10 Mar 2022	Severe microcephaly v2.287	ZNF335	Eleanor Williams Phenotypes for gene: ZNF335 were changed from Microcephaly 10, primary, autosomal recessive, 615095 to Microcephaly 10, primary, autosomal recessive, OMIM:615095
10 Mar 2022	Severe microcephaly v2.286	ZNF335	Eleanor Williams Tag for-review was removed from gene: ZNF335.
10 Mar 2022	Severe microcephaly v2.286	ATP1A2	Eleanor Williams Tag for-review was removed from gene: ATP1A2.
10 Mar 2022	Severe microcephaly v2.286	KIF14	Eleanor Williams Tag for-review was removed from gene: KIF14.
10 Mar 2022	Severe microcephaly v2.286	AP4E1	Eleanor Williams Tag for-review was removed from gene: AP4E1.
10 Mar 2022	Severe microcephaly v2.286	SVBP	Eleanor Williams Tag for-review was removed from gene: SVBP.
10 Mar 2022	Severe microcephaly v2.286	CEP55	Eleanor Williams Tag for-review was removed from gene: CEP55.
10 Mar 2022	Severe microcephaly v2.286	TMX2	Eleanor Williams Tag for-review was removed from gene: TMX2.
10 Mar 2022	Severe microcephaly v2.286	TUBGCP2	Eleanor Williams Phenotypes for gene: TUBGCP2 were changed from Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737 to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM:618737
10 Mar 2022	Severe microcephaly v2.285	TUBGCP2	Eleanor Williams Tag for-review was removed from gene: TUBGCP2.
10 Mar 2022	Severe microcephaly v2.285	TTC5	Eleanor Williams Tag for-review was removed from gene: TTC5.
10 Mar 2022	Severe microcephaly v2.285	NUP188	Eleanor Williams Phenotypes for gene: NUP188 were changed from Sandestig-Stefanova syndrome, 618804 to Sandestig-Stefanova syndrome, OMIM:618804
10 Mar 2022	Severe microcephaly v2.284	NUP188	Eleanor Williams Tag for-review was removed from gene: NUP188.
10 Mar 2022	Severe microcephaly v2.284	NCAPD2	Eleanor Williams Phenotypes for gene: NCAPD2 were changed from Microcephaly 21, primary, autosomal recessive, 617983 to Microcephaly 21, primary, autosomal recessive, OMIM:617983
10 Mar 2022	Severe microcephaly v2.283	NCAPD2	Eleanor Williams Tag for-review was removed from gene: NCAPD2.
10 Mar 2022	Severe microcephaly v2.283	ADARB1	Eleanor Williams Phenotypes for gene: ADARB1 were changed from Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862 to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, OMIM:618862
10 Mar 2022	Severe microcephaly v2.282	ADARB1	Eleanor Williams Tag for-review was removed from gene: ADARB1.
10 Mar 2022	Severe microcephaly v2.282	PPIL1	Eleanor Williams Tag for-review was removed from gene: PPIL1.
10 Mar 2022	Severe microcephaly v2.282	FBRSL1	Eleanor Williams Tag for-review was removed from gene: FBRSL1.
10 Mar 2022	Severe microcephaly v2.282	ANKLE2	Eleanor Williams Tag for-review was removed from gene: ANKLE2.
10 Mar 2022	Severe microcephaly v2.282	COASY	Eleanor Williams Tag watchlist was removed from gene: COASY. Tag for-review was removed from gene: COASY.
10 Mar 2022	Severe microcephaly v2.282	TRAPPC12	Eleanor Williams Tag for-review was removed from gene: TRAPPC12.
10 Mar 2022	Severe microcephaly v2.282	METTL5	Sarah Leigh commented on gene: METTL5
10 Mar 2022	Severe microcephaly v2.282	AP4S1	Sarah Leigh commented on gene: AP4S1: Comment from NHS Genomic Medicine Service: primary presentation is ID/DD/spasticity/hypotonia: green on ID and HSP and hypotonic infant panels - not clear if severe microephaly exists in absence of these.
10 Mar 2022	Severe microcephaly v2.282	AP4S1	Sarah Leigh commented on gene: AP4S1
10 Mar 2022	Severe microcephaly v2.282	AP4M1	Sarah Leigh commented on gene: AP4M1: Comment from NHS Genomic Medicine Service: primary presentation is ID/DD/spasticity/hypotonia: green on ID and HSP and hypotonic infant panels - not clear if severe microephaly exists in absence of these.
10 Mar 2022	Severe microcephaly v2.282	AP4M1	Sarah Leigh commented on gene: AP4M1
10 Mar 2022	Severe microcephaly v2.282	AP4B1	Sarah Leigh commented on gene: AP4B1: Comment from NHS Genomic Medicine Service: primary presentation is ID/DD/spasticity/hypotonia: green on ID and HSP and hypotonic infant panels - not clear if severe microephaly exists in absence of these
10 Mar 2022	Severe microcephaly v2.282	AP4B1	Sarah Leigh commented on gene: AP4B1
10 Mar 2022	Severe microcephaly v2.282	UBE3A	Sarah Leigh commented on gene: UBE3A: Comment from NHS Genomic Medicine Service: Primary presentation is ID/DD: green on ID & other panels - not clear if severe microephaly exists in absence of these other features? Microcephaly isn't listed as a key feature in Genereviews for females, ands is only present in some males (with severe epilepsy).
10 Mar 2022	Severe microcephaly v2.282	UBE3A	Sarah Leigh commented on gene: UBE3A: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.
10 Mar 2022	Severe microcephaly v2.282	ZNF526	Sarah Leigh commented on gene: ZNF526
10 Mar 2022	Severe microcephaly v2.282	SMG8	Sarah Leigh commented on gene: SMG8
10 Mar 2022	Severe microcephaly v2.282	NARS	Sarah Leigh commented on gene: NARS
10 Mar 2022	Severe microcephaly v2.282	MORC2	Sarah Leigh commented on gene: MORC2
10 Mar 2022	Severe microcephaly v2.282	LMNB2	Sarah Leigh commented on gene: LMNB2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	LMNB1	Sarah Leigh commented on gene: LMNB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	DNMT3A	Sarah Leigh commented on gene: DNMT3A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	ZNF335	Sarah Leigh commented on gene: ZNF335
10 Mar 2022	Severe microcephaly v2.282	ATP1A2	Sarah Leigh commented on gene: ATP1A2
10 Mar 2022	Severe microcephaly v2.282	KIF14	Sarah Leigh commented on gene: KIF14
10 Mar 2022	Severe microcephaly v2.282	AP4E1	Sarah Leigh commented on gene: AP4E1
10 Mar 2022	Severe microcephaly v2.282	SVBP	Sarah Leigh commented on gene: SVBP
10 Mar 2022	Severe microcephaly v2.282	CEP55	Sarah Leigh commented on gene: CEP55
10 Mar 2022	Severe microcephaly v2.282	TMX2	Sarah Leigh commented on gene: TMX2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	TUBGCP2	Sarah Leigh commented on gene: TUBGCP2
10 Mar 2022	Severe microcephaly v2.282	TTC5	Sarah Leigh commented on gene: TTC5: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	NUP188	Sarah Leigh commented on gene: NUP188
10 Mar 2022	Severe microcephaly v2.282	NCAPD2	Sarah Leigh commented on gene: NCAPD2
10 Mar 2022	Severe microcephaly v2.282	ADARB1	Sarah Leigh commented on gene: ADARB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	PPIL1	Sarah Leigh commented on gene: PPIL1
10 Mar 2022	Severe microcephaly v2.282	FBRSL1	Sarah Leigh commented on gene: FBRSL1
10 Mar 2022	Severe microcephaly v2.282	ANKLE2	Sarah Leigh commented on gene: ANKLE2
10 Mar 2022	Severe microcephaly v2.282	COASY	Sarah Leigh commented on gene: COASY: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
10 Mar 2022	Severe microcephaly v2.282	TRAPPC12	Sarah Leigh commented on gene: TRAPPC12
10 Mar 2022	Severe microcephaly v2.281	METTL5	Eleanor Williams Source Expert Review Green was added to METTL5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	ZNF526	Eleanor Williams Source Expert Review Green was added to ZNF526. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	SMG8	Eleanor Williams Source Expert Review Green was added to SMG8. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	NARS	Eleanor Williams Source Expert Review Green was added to NARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	MORC2	Eleanor Williams Source Expert Review Green was added to MORC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	LMNB2	Eleanor Williams Source Expert Review Green was added to LMNB2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	LMNB1	Eleanor Williams Source Expert Review Green was added to LMNB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	DNMT3A	Eleanor Williams Source Expert Review Green was added to DNMT3A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	ZNF335	Eleanor Williams Source Expert Review Green was added to ZNF335. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	ATP1A2	Eleanor Williams Source Expert Review Green was added to ATP1A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	KIF14	Eleanor Williams Source Expert Review Green was added to KIF14. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	AP4E1	Eleanor Williams Source Expert Review Green was added to AP4E1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	SVBP	Eleanor Williams Source Expert Review Green was added to SVBP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	CEP55	Eleanor Williams Source Expert Review Green was added to CEP55. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	TMX2	Eleanor Williams Source Expert Review Green was added to TMX2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	TUBGCP2	Eleanor Williams Source Expert Review Green was added to TUBGCP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	TTC5	Eleanor Williams Source Expert Review Green was added to TTC5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	NUP188	Eleanor Williams Source Expert Review Green was added to NUP188. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	NCAPD2	Eleanor Williams Source Expert Review Green was added to NCAPD2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	ADARB1	Eleanor Williams Source Expert Review Green was added to ADARB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	PPIL1	Eleanor Williams Source Expert Review Green was added to PPIL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	FBRSL1	Eleanor Williams Source Expert Review Green was added to FBRSL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	ANKLE2	Eleanor Williams Source Expert Review Green was added to ANKLE2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	COASY	Eleanor Williams Source Expert Review Green was added to COASY. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
10 Mar 2022	Severe microcephaly v2.281	TRAPPC12	Eleanor Williams Source Expert Review Green was added to TRAPPC12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ADGRG1	Eleanor Williams Tag Q2_21_phenotype was removed from gene: ADGRG1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AP1S2	Eleanor Williams Tag Q2_21_phenotype was removed from gene: AP1S2.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	XRCC1	Eleanor Williams Tag Q2_21_expert_review was removed from gene: XRCC1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	VPS41	Eleanor Williams Tag Q2_21_expert_review was removed from gene: VPS41. Tag Q2_21_NHS_review was removed from gene: VPS41.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	UCHL1	Eleanor Williams Tag Q2_21_expert_review was removed from gene: UCHL1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	TSEN15	Eleanor Williams Tag Q2_21_rating was removed from gene: TSEN15.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	TBC1D23	Eleanor Williams Tag Q2_21_phenotype was removed from gene: TBC1D23.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	SLC9A1	Eleanor Williams Tag Q2_21_phenotype was removed from gene: SLC9A1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	SCYL1	Eleanor Williams Tag Q2_21_phenotype was removed from gene: SCYL1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	RORA	Eleanor Williams Tag Q2_21_phenotype was removed from gene: RORA.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	PRICKLE1	Eleanor Williams Tag Q2_21_phenotype was removed from gene: PRICKLE1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	MAPK8IP3	Eleanor Williams Tag Q4_21_rating was removed from gene: MAPK8IP3.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ERCC4	Eleanor Williams Tag Q2_21_rating was removed from gene: ERCC4.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	EBF3	Eleanor Williams Tag Q2_21_phenotype was removed from gene: EBF3.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	CLP1	Eleanor Williams Tag Q2_21_phenotype was removed from gene: CLP1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	CHMP1A	Eleanor Williams Tag Q2_21_phenotype was removed from gene: CHMP1A.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	B4GAT1	Eleanor Williams Tag Q3_21_rating was removed from gene: B4GAT1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AUH	Eleanor Williams Tag Q2_21_rating was removed from gene: AUH.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ATP8A2	Eleanor Williams Tag Q2_21_phenotype was removed from gene: ATP8A2. Tag Q2_21_expert_review was removed from gene: ATP8A2.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AMPD2	Eleanor Williams Tag Q2_21_phenotype was removed from gene: AMPD2.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ADPRHL2	Eleanor Williams Tag Q2_21_expert_review was removed from gene: ADPRHL2.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ABCB7	Eleanor Williams Tag Q2_21_phenotype was removed from gene: ABCB7.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	XRCC1	Sarah Leigh commented on gene: XRCC1
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	VPS41	Sarah Leigh commented on gene: VPS41
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	UCHL1	Sarah Leigh commented on gene: UCHL1
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	TSEN15	Sarah Leigh commented on gene: TSEN15
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	TBC1D23	Sarah Leigh commented on gene: TBC1D23: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	SLC9A1	Sarah Leigh commented on gene: SLC9A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	SCYL1	Sarah Leigh commented on gene: SCYL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	RORA	Sarah Leigh commented on gene: RORA: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	PRICKLE1	Sarah Leigh commented on gene: PRICKLE1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	MAPK8IP3	Sarah Leigh commented on gene: MAPK8IP3
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ERCC4	Sarah Leigh commented on gene: ERCC4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	EBF3	Sarah Leigh commented on gene: EBF3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	CLP1	Sarah Leigh commented on gene: CLP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	CHMP1A	Sarah Leigh commented on gene: CHMP1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	B4GAT1	Sarah Leigh commented on gene: B4GAT1
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AUH	Sarah Leigh commented on gene: AUH
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ATP8A2	Sarah Leigh commented on gene: ATP8A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AP1S2	Sarah Leigh commented on gene: AP1S2
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	AMPD2	Sarah Leigh commented on gene: AMPD2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ADPRHL2	Sarah Leigh commented on gene: ADPRHL2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ADGRG1	Sarah Leigh commented on gene: ADGRG1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.144	ABCB7	Sarah Leigh commented on gene: ABCB7: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	UCHL1	Eleanor Williams Source Expert Review Amber was added to UCHL1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	TSEN15	Eleanor Williams Source Expert Review Red was added to TSEN15. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	TBC1D23	Eleanor Williams Source Expert Review Amber was added to TBC1D23. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	SLC9A1	Eleanor Williams Source Expert Review Amber was added to SLC9A1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	SCYL1	Eleanor Williams Source Expert Review Amber was added to SCYL1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	RORA	Eleanor Williams Source Expert Review Amber was added to RORA. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	PRICKLE1	Eleanor Williams Source Expert Review Amber was added to PRICKLE1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	MAPK8IP3	Eleanor Williams Source Expert Review Red was added to MAPK8IP3. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	ERCC4	Eleanor Williams Source Expert Review Green was added to ERCC4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	EBF3	Eleanor Williams Source Expert Review Amber was added to EBF3. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	CLP1	Eleanor Williams Source Expert Review Amber was added to CLP1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	CHMP1A	Eleanor Williams Source Expert Review Amber was added to CHMP1A. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	B4GAT1	Eleanor Williams Source Expert Review Red was added to B4GAT1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	AUH	Eleanor Williams Source Expert Review Green was added to AUH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	ATP8A2	Eleanor Williams Source Expert Review Amber was added to ATP8A2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	AP1S2	Eleanor Williams Source Expert Review Amber was added to AP1S2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	AMPD2	Eleanor Williams Source Expert Review Amber was added to AMPD2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	ADPRHL2	Eleanor Williams Source Expert Review Amber was added to ADPRHL2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	ADGRG1	Eleanor Williams Source Expert Review Amber was added to ADGRG1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.143	ABCB7	Eleanor Williams Source Expert Review Amber was added to ABCB7. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1511	RNF113A	Arina Puzriakova Tag for-review was removed from gene: RNF113A.
09 Mar 2022	Intellectual disability v3.1511	GAD1	Arina Puzriakova Tag for-review was removed from gene: GAD1.
09 Mar 2022	Intellectual disability v3.1511	ALG9	Arina Puzriakova Tag for-review was removed from gene: ALG9.
09 Mar 2022	Intellectual disability v3.1511	STT3A	Arina Puzriakova Tag for-review was removed from gene: STT3A.
09 Mar 2022	Intellectual disability v3.1511	NEDD4L	Arina Puzriakova Tag for-review was removed from gene: NEDD4L.
09 Mar 2022	Intellectual disability v3.1511	MADD	Arina Puzriakova Mode of inheritance for gene: MADD was changed from to BIALLELIC, autosomal or pseudoautosomal
09 Mar 2022	Intellectual disability v3.1510	MADD	Arina Puzriakova Tag for-review was removed from gene: MADD.
09 Mar 2022	Intellectual disability v3.1510	KDM6B	Arina Puzriakova Tag for-review was removed from gene: KDM6B.
09 Mar 2022	Intellectual disability v3.1510	HERC2	Arina Puzriakova Tag for-review was removed from gene: HERC2.
09 Mar 2022	Intellectual disability v3.1510	AHCY	Arina Puzriakova Tag for-review was removed from gene: AHCY.
09 Mar 2022	Intellectual disability v3.1510	PIGP	Arina Puzriakova Tag for-review was removed from gene: PIGP.
09 Mar 2022	Intellectual disability v3.1510	RNF13	Arina Puzriakova Tag watchlist was removed from gene: RNF13. Tag for-review was removed from gene: RNF13.
09 Mar 2022	Intellectual disability v3.1510	PTRHD1	Arina Puzriakova Tag for-review was removed from gene: PTRHD1.
09 Mar 2022	Intellectual disability v3.1510	XYLT1	Arina Puzriakova Tag for-review was removed from gene: XYLT1.
09 Mar 2022	Intellectual disability v3.1510	WDFY3	Arina Puzriakova Tag for-review was removed from gene: WDFY3.
09 Mar 2022	Intellectual disability v3.1510	USP7	Arina Puzriakova Tag for-review was removed from gene: USP7.
09 Mar 2022	Intellectual disability v3.1510	TRPM3	Arina Puzriakova Tag watchlist was removed from gene: TRPM3. Tag for-review was removed from gene: TRPM3.
09 Mar 2022	Intellectual disability v3.1510	NR4A2	Arina Puzriakova Tag watchlist was removed from gene: NR4A2. Tag for-review was removed from gene: NR4A2.
09 Mar 2022	Intellectual disability v3.1510	CEP104	Arina Puzriakova Tag for-review was removed from gene: CEP104.
09 Mar 2022	Intellectual disability v3.1510	C2CD3	Arina Puzriakova Tag for-review was removed from gene: C2CD3.
09 Mar 2022	Intellectual disability v3.1510	ATP1A2	Arina Puzriakova Tag for-review was removed from gene: ATP1A2.
09 Mar 2022	Intellectual disability v3.1510	ABAT	Arina Puzriakova Tag for-review was removed from gene: ABAT.
09 Mar 2022	Intellectual disability v3.1510	TCTN3	Arina Puzriakova Tag for-review was removed from gene: TCTN3.
09 Mar 2022	Intellectual disability v3.1510	TOR1A	Arina Puzriakova Tag for-review was removed from gene: TOR1A.
09 Mar 2022	Intellectual disability v3.1510	TANC2	Arina Puzriakova Tag for-review was removed from gene: TANC2.
09 Mar 2022	Intellectual disability v3.1510	ADAM22	Arina Puzriakova Tag for-review was removed from gene: ADAM22.
09 Mar 2022	Intellectual disability v3.1510	UBR7	Arina Puzriakova Tag for-review was removed from gene: UBR7.
09 Mar 2022	Intellectual disability v3.1510	VPS4A	Arina Puzriakova Tag for-review was removed from gene: VPS4A.
09 Mar 2022	Intellectual disability v3.1510	RNU7-1	Arina Puzriakova Tag for-review was removed from gene: RNU7-1.
09 Mar 2022	Intellectual disability v3.1510	PPIL1	Arina Puzriakova Tag for-review was removed from gene: PPIL1.
09 Mar 2022	Intellectual disability v3.1510	FBRSL1	Arina Puzriakova Tag for-review was removed from gene: FBRSL1.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.142	TMEM106B	Eleanor Williams Publications for gene: TMEM106B were set to
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.141	TMEM106B	Eleanor Williams Tag for-review was removed from gene: TMEM106B.
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.141	TMEM106B	Sarah Leigh commented on gene: TMEM106B
09 Mar 2022	Hereditary ataxia with onset in adulthood v2.140	TMEM106B	Eleanor Williams Source Expert Review Amber was added to TMEM106B. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	RNU7-1	Ivone Leong Tag for-review was removed from gene: RNU7-1.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	NUP188	Ivone Leong Tag watchlist was removed from gene: NUP188.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	NUP188	Ivone Leong Tag for-review was removed from gene: NUP188. Tag watchlist tag was added to gene: NUP188.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	SCAF4	Ivone Leong Tag for-review was removed from gene: SCAF4.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	AP4B1	Ivone Leong Tag for-review was removed from gene: AP4B1.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	TMEM106B	Ivone Leong Tag for-review was removed from gene: TMEM106B.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	STN1	Ivone Leong Tag for-review was removed from gene: STN1.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	STN1	Sarah Leigh commented on gene: STN1: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	TMEM106B	Sarah Leigh commented on gene: TMEM106B
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	AP4B1	Sarah Leigh commented on gene: AP4B1
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	SCAF4	Sarah Leigh commented on gene: SCAF4
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	NUP188	Sarah Leigh commented on gene: NUP188
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	RNU7-1	Sarah Leigh commented on gene: RNU7-1
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	STN1	Ivone Leong Source Expert Review Green was added to STN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	TMEM106B	Ivone Leong Source Expert Review Green was added to TMEM106B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	AP4B1	Ivone Leong Source Expert Review Green was added to AP4B1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	SCAF4	Ivone Leong Source Expert Review Green was added to SCAF4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	NUP188	Ivone Leong Source Expert Review Green was added to NUP188. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	White matter disorders and cerebral calcification - narrow panel v1.223	RNU7-1	Ivone Leong Source Expert Review Green was added to RNU7-1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Holoprosencephaly v2.25	SMC1A	Ivone Leong Tag for-review was removed from gene: SMC1A.
09 Mar 2022	Holoprosencephaly v2.25	STAG2	Ivone Leong Tag for-review was removed from gene: STAG2.
09 Mar 2022	Holoprosencephaly v2.25	STAG2	Sarah Leigh commented on gene: STAG2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Holoprosencephaly v2.25	SMC1A	Sarah Leigh commented on gene: SMC1A
09 Mar 2022	Holoprosencephaly v2.24	STAG2	Ivone Leong Source Expert Review Green was added to STAG2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Holoprosencephaly v2.24	SMC1A	Ivone Leong Source Expert Review Green was added to SMC1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	RNU7-1	Ivone Leong Tag for-review was removed from gene: RNU7-1.
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	PCYT2	Ivone Leong Tag for-review was removed from gene: PCYT2.
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	STN1	Ivone Leong Tag for-review was removed from gene: STN1.
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	STN1	Sarah Leigh commented on gene: STN1: The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	PCYT2	Sarah Leigh commented on gene: PCYT2
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.125	RNU7-1	Sarah Leigh commented on gene: RNU7-1
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.124	STN1	Ivone Leong Source Expert Review Green was added to STN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.124	PCYT2	Ivone Leong Source Expert Review Green was added to PCYT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Childhood onset hereditary spastic paraplegia v2.124	RNU7-1	Ivone Leong Source Expert Review Green was added to RNU7-1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Congenital myopathy v2.74	GFER	Ivone Leong Tag for-review was removed from gene: GFER.
09 Mar 2022	Congenital myopathy v2.74	KY	Ivone Leong Tag watchlist was removed from gene: KY. Tag for-review was removed from gene: KY.
09 Mar 2022	Congenital myopathy v2.74	UNC45B	Ivone Leong Tag for-review was removed from gene: UNC45B.
09 Mar 2022	Congenital myopathy v2.74	MYH2	Ivone Leong Tag for-review was removed from gene: MYH2.
09 Mar 2022	Congenital myopathy v2.74	MYH2	Sarah Leigh reviewed gene: MYH2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
09 Mar 2022	Congenital myopathy v2.74	UNC45B	Sarah Leigh commented on gene: UNC45B: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
09 Mar 2022	Congenital myopathy v2.74	KY	Sarah Leigh commented on gene: KY: The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
09 Mar 2022	Congenital myopathy v2.74	GFER	Sarah Leigh commented on gene: GFER
09 Mar 2022	Congenital myopathy v2.73	MYH2	Ivone Leong Source Expert list was added to MYH2. Mode of inheritance for gene MYH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
09 Mar 2022	Congenital myopathy v2.73	UNC45B	Ivone Leong Source Expert Review Green was added to UNC45B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Congenital myopathy v2.73	KY	Ivone Leong Source Expert Review Green was added to KY. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Congenital myopathy v2.73	GFER	Ivone Leong Source Expert Review Green was added to GFER. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1510	CACNB4	Sarah Leigh commented on gene: CACNB4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	CNOT3	Sarah Leigh commented on gene: CNOT3: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	ZNF335	Sarah Leigh commented on gene: ZNF335: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	MFSD2A	Sarah Leigh commented on gene: MFSD2A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	MAPRE2	Sarah Leigh commented on gene: MAPRE2: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	SCN1B	Sarah Leigh commented on gene: SCN1B
09 Mar 2022	Intellectual disability v3.1510	SCAMP5	Sarah Leigh commented on gene: SCAMP5: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	KAT8	Sarah Leigh commented on gene: KAT8: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	GPC4	Sarah Leigh commented on gene: GPC4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	KDM6B	Sarah Leigh commented on gene: KDM6B: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	CDK19	Sarah Leigh commented on gene: CDK19: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	EXT2	Sarah Leigh commented on gene: EXT2: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	TOR1A	Sarah Leigh commented on gene: TOR1A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	ABCA2	Sarah Leigh commented on gene: ABCA2
09 Mar 2022	Intellectual disability v3.1510	PIGH	Sarah Leigh commented on gene: PIGH
09 Mar 2022	Intellectual disability v3.1510	METTL5	Sarah Leigh commented on gene: METTL5
09 Mar 2022	Intellectual disability v3.1510	LMBRD2	Sarah Leigh commented on gene: LMBRD2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	LIAS	Sarah Leigh commented on gene: LIAS
09 Mar 2022	Intellectual disability v3.1510	CSNK1G1	Sarah Leigh commented on gene: CSNK1G1
09 Mar 2022	Intellectual disability v3.1510	ALG14	Sarah Leigh commented on gene: ALG14: After NHSGenomic Medicine Service consideration, the rating of this gene has not been changed.
09 Mar 2022	Intellectual disability v3.1510	SLC12A6	Sarah Leigh commented on gene: SLC12A6: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	COG4	Sarah Leigh commented on gene: COG4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	SCN8A	Sarah Leigh commented on gene: SCN8A: Just 2 families reported with possible AR inheritance: v rare - all het parents seem to have features so prob ok to keep as monoallelic only (source NHS Genomic Medicine Service).
09 Mar 2022	Intellectual disability v3.1510	SCN8A	Sarah Leigh commented on gene: SCN8A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
09 Mar 2022	Intellectual disability v3.1510	AGO2	Sarah Leigh commented on gene: AGO2: Green rating is for monoallelic MOI only, many cases reported with speech delay and variable ID (source NHS Genomic Medicine Service).
09 Mar 2022	Intellectual disability v3.1510	AGO2	Sarah Leigh commented on gene: AGO2
09 Mar 2022	Intellectual disability v3.1510	PNPT1	Sarah Leigh commented on gene: PNPT1
09 Mar 2022	Intellectual disability v3.1510	SCO1	Sarah Leigh commented on gene: SCO1
09 Mar 2022	Intellectual disability v3.1510	FA2H	Sarah Leigh commented on gene: FA2H: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	COX6B1	Sarah Leigh commented on gene: COX6B1
09 Mar 2022	Intellectual disability v3.1510	MPI	Sarah Leigh commented on gene: MPI
09 Mar 2022	Intellectual disability v3.1510	VAMP1	Sarah Leigh commented on gene: VAMP1
09 Mar 2022	Intellectual disability v3.1510	TRIM32	Sarah Leigh commented on gene: TRIM32
09 Mar 2022	Intellectual disability v3.1510	MGP	Sarah Leigh commented on gene: MGP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	LGI4	Sarah Leigh commented on gene: LGI4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	HYLS1	Sarah Leigh commented on gene: HYLS1
09 Mar 2022	Intellectual disability v3.1510	HADH	Sarah Leigh commented on gene: HADH
09 Mar 2022	Intellectual disability v3.1510	FLVCR1	Sarah Leigh commented on gene: FLVCR1
09 Mar 2022	Intellectual disability v3.1510	ATL1	Sarah Leigh commented on gene: ATL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	ANKH	Sarah Leigh commented on gene: ANKH: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	AFG3L2	Sarah Leigh commented on gene: AFG3L2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	KCNC3	Sarah Leigh commented on gene: KCNC3
09 Mar 2022	Intellectual disability v3.1510	ALKBH8	Sarah Leigh commented on gene: ALKBH8
09 Mar 2022	Intellectual disability v3.1510	SOX3	Sarah Leigh commented on gene: SOX3
09 Mar 2022	Intellectual disability v3.1510	PRKD1	Sarah Leigh commented on gene: PRKD1
09 Mar 2022	Intellectual disability v3.1510	GPSM2	Sarah Leigh commented on gene: GPSM2
09 Mar 2022	Intellectual disability v3.1510	DDOST	Sarah Leigh commented on gene: DDOST
09 Mar 2022	Intellectual disability v3.1510	CYP2U1	Sarah Leigh commented on gene: CYP2U1
09 Mar 2022	Intellectual disability v3.1510	AGPS	Sarah Leigh commented on gene: AGPS
09 Mar 2022	Intellectual disability v3.1510	TMEM106B	Sarah Leigh commented on gene: TMEM106B
09 Mar 2022	Intellectual disability v3.1510	NEMF	Sarah Leigh commented on gene: NEMF
09 Mar 2022	Intellectual disability v3.1510	MPP5	Sarah Leigh commented on gene: MPP5
09 Mar 2022	Intellectual disability v3.1510	MAPK1	Sarah Leigh commented on gene: MAPK1
09 Mar 2022	Intellectual disability v3.1510	LMNB1	Sarah Leigh commented on gene: LMNB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	KIF21B	Sarah Leigh commented on gene: KIF21B
09 Mar 2022	Intellectual disability v3.1510	JARID2	Sarah Leigh commented on gene: JARID2
09 Mar 2022	Intellectual disability v3.1510	FAM50A	Sarah Leigh commented on gene: FAM50A
09 Mar 2022	Intellectual disability v3.1510	CEP120	Sarah Leigh commented on gene: CEP120
09 Mar 2022	Intellectual disability v3.1510	ZNF526	Sarah Leigh commented on gene: ZNF526
09 Mar 2022	Intellectual disability v3.1510	TFE3	Sarah Leigh commented on gene: TFE3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PIGQ	Sarah Leigh commented on gene: PIGQ: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	KAT5	Sarah Leigh commented on gene: KAT5
09 Mar 2022	Intellectual disability v3.1510	ZNF335	Sarah Leigh commented on gene: ZNF335
09 Mar 2022	Intellectual disability v3.1510	ZIC1	Sarah Leigh commented on gene: ZIC1
09 Mar 2022	Intellectual disability v3.1510	SETD1A	Sarah Leigh commented on gene: SETD1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PET100	Sarah Leigh commented on gene: PET100
09 Mar 2022	Intellectual disability v3.1510	NUDT2	Sarah Leigh commented on gene: NUDT2
09 Mar 2022	Intellectual disability v3.1510	MFSD2A	Sarah Leigh commented on gene: MFSD2A
09 Mar 2022	Intellectual disability v3.1510	MAPRE2	Sarah Leigh commented on gene: MAPRE2
09 Mar 2022	Intellectual disability v3.1510	CDH2	Sarah Leigh commented on gene: CDH2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SMG8	Sarah Leigh commented on gene: SMG8
09 Mar 2022	Intellectual disability v3.1510	LSS	Sarah Leigh commented on gene: LSS
09 Mar 2022	Intellectual disability v3.1510	KCNMA1	Sarah Leigh commented on gene: KCNMA1
09 Mar 2022	Intellectual disability v3.1510	H3F3B	Sarah Leigh commented on gene: H3F3B
09 Mar 2022	Intellectual disability v3.1510	H3F3A	Sarah Leigh commented on gene: H3F3A
09 Mar 2022	Intellectual disability v3.1510	KDM4B	Sarah Leigh commented on gene: KDM4B
09 Mar 2022	Intellectual disability v3.1510	BICRA	Sarah Leigh commented on gene: BICRA
09 Mar 2022	Intellectual disability v3.1510	ZFHX4	Sarah Leigh commented on gene: ZFHX4
09 Mar 2022	Intellectual disability v3.1510	SHMT2	Sarah Leigh commented on gene: SHMT2
09 Mar 2022	Intellectual disability v3.1510	NARS	Sarah Leigh commented on gene: NARS
09 Mar 2022	Intellectual disability v3.1510	MORC2	Sarah Leigh commented on gene: MORC2
09 Mar 2022	Intellectual disability v3.1510	LARS	Sarah Leigh commented on gene: LARS
09 Mar 2022	Intellectual disability v3.1510	POLR1C	Sarah Leigh commented on gene: POLR1C
09 Mar 2022	Intellectual disability v3.1510	NUS1	Sarah Leigh commented on gene: NUS1
09 Mar 2022	Intellectual disability v3.1510	PUM1	Sarah Leigh commented on gene: PUM1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	RALGAPA1	Sarah Leigh commented on gene: RALGAPA1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	RARS	Sarah Leigh commented on gene: RARS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	CEP55	Sarah Leigh commented on gene: CEP55
09 Mar 2022	Intellectual disability v3.1510	CTU2	Sarah Leigh commented on gene: CTU2
09 Mar 2022	Intellectual disability v3.1510	TRAPPC4	Sarah Leigh commented on gene: TRAPPC4
09 Mar 2022	Intellectual disability v3.1510	UGP2	Sarah Leigh commented on gene: UGP2
09 Mar 2022	Intellectual disability v3.1510	CXorf56	Sarah Leigh commented on gene: CXorf56
09 Mar 2022	Intellectual disability v3.1510	KAT8	Sarah Leigh commented on gene: KAT8
09 Mar 2022	Intellectual disability v3.1510	SLC5A6	Sarah Leigh commented on gene: SLC5A6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SNX27	Sarah Leigh commented on gene: SNX27: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	WNT1	Sarah Leigh commented on gene: WNT1
09 Mar 2022	Intellectual disability v3.1510	YIF1B	Sarah Leigh commented on gene: YIF1B
09 Mar 2022	Intellectual disability v3.1510	VARS2	Sarah Leigh commented on gene: VARS2
09 Mar 2022	Intellectual disability v3.1510	UGDH	Sarah Leigh commented on gene: UGDH
09 Mar 2022	Intellectual disability v3.1510	TTC5	Sarah Leigh commented on gene: TTC5: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	TRNT1	Sarah Leigh commented on gene: TRNT1
09 Mar 2022	Intellectual disability v3.1510	TNRC6B	Sarah Leigh commented on gene: TNRC6B
09 Mar 2022	Intellectual disability v3.1510	TET3	Sarah Leigh commented on gene: TET3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	TENM3	Sarah Leigh commented on gene: TENM3
09 Mar 2022	Intellectual disability v3.1510	TASP1	Sarah Leigh commented on gene: TASP1
09 Mar 2022	Intellectual disability v3.1510	SUZ12	Sarah Leigh commented on gene: SUZ12: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SUPT16H	Sarah Leigh commented on gene: SUPT16H
09 Mar 2022	Intellectual disability v3.1510	SPTBN4	Sarah Leigh commented on gene: SPTBN4
09 Mar 2022	Intellectual disability v3.1510	SPOP	Sarah Leigh commented on gene: SPOP
09 Mar 2022	Intellectual disability v3.1510	SOX6	Sarah Leigh commented on gene: SOX6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SLC1A1	Sarah Leigh commented on gene: SLC1A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SLC12A2	Sarah Leigh commented on gene: SLC12A2
09 Mar 2022	Intellectual disability v3.1510	SFXN4	Sarah Leigh commented on gene: SFXN4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SBF1	Sarah Leigh commented on gene: SBF1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	SARS2	Sarah Leigh commented on gene: SARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	RSRC1	Sarah Leigh commented on gene: RSRC1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PPP1R12A	Sarah Leigh commented on gene: PPP1R12A
09 Mar 2022	Intellectual disability v3.1510	PIGS	Sarah Leigh commented on gene: PIGS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PIGK	Sarah Leigh commented on gene: PIGK: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PIBF1	Sarah Leigh commented on gene: PIBF1
09 Mar 2022	Intellectual disability v3.1510	PDHB	Sarah Leigh commented on gene: PDHB
09 Mar 2022	Intellectual disability v3.1510	OXR1	Sarah Leigh commented on gene: OXR1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	NRROS	Sarah Leigh commented on gene: NRROS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	NOVA2	Sarah Leigh commented on gene: NOVA2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	NDUFA2	Sarah Leigh commented on gene: NDUFA2
09 Mar 2022	Intellectual disability v3.1510	MTHFS	Sarah Leigh commented on gene: MTHFS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	MN1	Sarah Leigh commented on gene: MN1
09 Mar 2022	Intellectual disability v3.1510	LYRM7	Sarah Leigh commented on gene: LYRM7
09 Mar 2022	Intellectual disability v3.1510	LIPT1	Sarah Leigh commented on gene: LIPT1
09 Mar 2022	Intellectual disability v3.1510	KLF7	Sarah Leigh commented on gene: KLF7
09 Mar 2022	Intellectual disability v3.1510	KCNN3	Sarah Leigh commented on gene: KCNN3
09 Mar 2022	Intellectual disability v3.1510	HNRNPH1	Sarah Leigh commented on gene: HNRNPH1
09 Mar 2022	Intellectual disability v3.1510	GPC4	Sarah Leigh commented on gene: GPC4
09 Mar 2022	Intellectual disability v3.1510	GALNT2	Sarah Leigh commented on gene: GALNT2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	EIF2AK2	Sarah Leigh commented on gene: EIF2AK2
09 Mar 2022	Intellectual disability v3.1510	EARS2	Sarah Leigh commented on gene: EARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	DNM1L	Sarah Leigh commented on gene: DNM1L
09 Mar 2022	Intellectual disability v3.1510	DHX37	Sarah Leigh commented on gene: DHX37
09 Mar 2022	Intellectual disability v3.1510	CTNND1	Sarah Leigh commented on gene: CTNND1
09 Mar 2022	Intellectual disability v3.1510	CNTNAP1	Sarah Leigh commented on gene: CNTNAP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	B9D2	Sarah Leigh commented on gene: B9D2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	ATAD1	Sarah Leigh commented on gene: ATAD1
09 Mar 2022	Intellectual disability v3.1510	ADD3	Sarah Leigh commented on gene: ADD3
09 Mar 2022	Intellectual disability v3.1510	ADARB1	Sarah Leigh commented on gene: ADARB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	DLL1	Sarah Leigh commented on gene: DLL1
09 Mar 2022	Intellectual disability v3.1510	RNF113A	Sarah Leigh commented on gene: RNF113A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	GAD1	Sarah Leigh commented on gene: GAD1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	ALG9	Sarah Leigh commented on gene: ALG9: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	STT3A	Sarah Leigh commented on gene: STT3A
09 Mar 2022	Intellectual disability v3.1510	NEDD4L	Sarah Leigh commented on gene: NEDD4L
09 Mar 2022	Intellectual disability v3.1510	MADD	Sarah Leigh commented on gene: MADD
09 Mar 2022	Intellectual disability v3.1510	KDM6B	Sarah Leigh commented on gene: KDM6B
09 Mar 2022	Intellectual disability v3.1510	HERC2	Sarah Leigh commented on gene: HERC2
09 Mar 2022	Intellectual disability v3.1510	CDK19	Sarah Leigh commented on gene: CDK19: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	AHCY	Sarah Leigh commented on gene: AHCY: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	PIGP	Sarah Leigh commented on gene: PIGP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	RNF13	Sarah Leigh commented on gene: RNF13: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	EXT2	Sarah Leigh commented on gene: EXT2
09 Mar 2022	Intellectual disability v3.1510	PTRHD1	Sarah Leigh commented on gene: PTRHD1
09 Mar 2022	Intellectual disability v3.1510	XYLT1	Sarah Leigh commented on gene: XYLT1
09 Mar 2022	Intellectual disability v3.1510	WDFY3	Sarah Leigh commented on gene: WDFY3
09 Mar 2022	Intellectual disability v3.1510	USP7	Sarah Leigh commented on gene: USP7
09 Mar 2022	Intellectual disability v3.1510	TRPM3	Sarah Leigh commented on gene: TRPM3
09 Mar 2022	Intellectual disability v3.1510	NR4A2	Sarah Leigh commented on gene: NR4A2
09 Mar 2022	Intellectual disability v3.1510	CEP104	Sarah Leigh commented on gene: CEP104
09 Mar 2022	Intellectual disability v3.1510	C2CD3	Sarah Leigh commented on gene: C2CD3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	ATP1A2	Sarah Leigh commented on gene: ATP1A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	ABAT	Sarah Leigh commented on gene: ABAT: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	TCTN3	Sarah Leigh commented on gene: TCTN3
09 Mar 2022	Intellectual disability v3.1510	TOR1A	Sarah Leigh commented on gene: TOR1A
09 Mar 2022	Intellectual disability v3.1510	TANC2	Sarah Leigh commented on gene: TANC2
09 Mar 2022	Intellectual disability v3.1510	ADAM22	Sarah Leigh commented on gene: ADAM22: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
09 Mar 2022	Intellectual disability v3.1510	UBR7	Sarah Leigh commented on gene: UBR7
09 Mar 2022	Intellectual disability v3.1510	VPS4A	Sarah Leigh commented on gene: VPS4A
09 Mar 2022	Intellectual disability v3.1510	RNU7-1	Sarah Leigh commented on gene: RNU7-1
09 Mar 2022	Intellectual disability v3.1510	PPIL1	Sarah Leigh commented on gene: PPIL1
09 Mar 2022	Intellectual disability v3.1510	FBRSL1	Sarah Leigh commented on gene: FBRSL1
09 Mar 2022	Intellectual disability v3.1509	CACNB4	Arina Puzriakova Source NHS GMS was added to CACNB4.
09 Mar 2022	Intellectual disability v3.1509	CNOT3	Arina Puzriakova Source NHS GMS was added to CNOT3.
09 Mar 2022	Intellectual disability v3.1509	ZNF335	Arina Puzriakova Source NHS GMS was added to ZNF335.
09 Mar 2022	Intellectual disability v3.1509	MFSD2A	Arina Puzriakova Source NHS GMS was added to MFSD2A.
09 Mar 2022	Intellectual disability v3.1509	MAPRE2	Arina Puzriakova Source NHS GMS was added to MAPRE2.
09 Mar 2022	Intellectual disability v3.1509	SCN1B	Arina Puzriakova Source NHS GMS was added to SCN1B.
09 Mar 2022	Intellectual disability v3.1509	SCAMP5	Arina Puzriakova Source NHS GMS was added to SCAMP5.
09 Mar 2022	Intellectual disability v3.1509	KAT8	Arina Puzriakova Source NHS GMS was added to KAT8.
09 Mar 2022	Intellectual disability v3.1509	GPC4	Arina Puzriakova Source NHS GMS was added to GPC4.
09 Mar 2022	Intellectual disability v3.1509	KDM6B	Arina Puzriakova Source NHS GMS was added to KDM6B.
09 Mar 2022	Intellectual disability v3.1509	CDK19	Arina Puzriakova Source NHS GMS was added to CDK19.
09 Mar 2022	Intellectual disability v3.1509	EXT2	Arina Puzriakova Source NHS GMS was added to EXT2.
09 Mar 2022	Intellectual disability v3.1509	TOR1A	Arina Puzriakova Source NHS GMS was added to TOR1A.
09 Mar 2022	Intellectual disability v3.1509	ABCA2	Arina Puzriakova Source Expert Review Green was added to ABCA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIGH	Arina Puzriakova Source Expert Review Green was added to PIGH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	METTL5	Arina Puzriakova Source Expert Review Green was added to METTL5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LMBRD2	Arina Puzriakova Source Expert Review Green was added to LMBRD2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LIAS	Arina Puzriakova Source Expert Review Green was added to LIAS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CSNK1G1	Arina Puzriakova Source Expert Review Green was added to CSNK1G1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	AGO2	Arina Puzriakova Source Expert Review Green was added to AGO2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PNPT1	Arina Puzriakova Source Expert Review Green was added to PNPT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SCO1	Arina Puzriakova Source Expert Review Red was added to SCO1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	FA2H	Arina Puzriakova Source Expert Review Red was added to FA2H. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	COX6B1	Arina Puzriakova Source Expert Review Red was added to COX6B1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	MPI	Arina Puzriakova Source Expert Review Red was added to MPI. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	VAMP1	Arina Puzriakova Source Expert Review Red was added to VAMP1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	TRIM32	Arina Puzriakova Source Expert Review Red was added to TRIM32. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	MGP	Arina Puzriakova Source Expert Review Red was added to MGP. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	LGI4	Arina Puzriakova Source Expert Review Red was added to LGI4. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	HYLS1	Arina Puzriakova Source Expert Review Red was added to HYLS1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	HADH	Arina Puzriakova Source Expert Review Red was added to HADH. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	FLVCR1	Arina Puzriakova Source Expert Review Red was added to FLVCR1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	ATL1	Arina Puzriakova Source Expert Review Red was added to ATL1. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	ANKH	Arina Puzriakova Source Expert Review Red was added to ANKH. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	AFG3L2	Arina Puzriakova Source Expert Review Red was added to AFG3L2. Rating Changed from Green List (high evidence) to Red List (low evidence)
09 Mar 2022	Intellectual disability v3.1509	KCNC3	Arina Puzriakova Source Expert Review Amber was added to KCNC3. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	ALKBH8	Arina Puzriakova Source Expert Review Amber was added to ALKBH8. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	SOX3	Arina Puzriakova Source Expert Review Amber was added to SOX3. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	PRKD1	Arina Puzriakova Source Expert Review Amber was added to PRKD1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	GPSM2	Arina Puzriakova Source Expert Review Amber was added to GPSM2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	DDOST	Arina Puzriakova Source Expert Review Amber was added to DDOST. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	CYP2U1	Arina Puzriakova Source Expert Review Amber was added to CYP2U1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	AGPS	Arina Puzriakova Source Expert Review Amber was added to AGPS. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
09 Mar 2022	Intellectual disability v3.1509	TMEM106B	Arina Puzriakova Source Expert Review Green was added to TMEM106B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NEMF	Arina Puzriakova Source Expert Review Green was added to NEMF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MPP5	Arina Puzriakova Source Expert Review Green was added to MPP5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MAPK1	Arina Puzriakova Source Expert Review Green was added to MAPK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LMNB1	Arina Puzriakova Source Expert Review Green was added to LMNB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KIF21B	Arina Puzriakova Source Expert Review Green was added to KIF21B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	JARID2	Arina Puzriakova Source Expert Review Green was added to JARID2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	FAM50A	Arina Puzriakova Source Expert Review Green was added to FAM50A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CEP120	Arina Puzriakova Source Expert Review Green was added to CEP120. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ZNF526	Arina Puzriakova Source Expert Review Green was added to ZNF526. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TFE3	Arina Puzriakova Source Expert Review Green was added to TFE3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIGQ	Arina Puzriakova Source Expert Review Green was added to PIGQ. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KAT5	Arina Puzriakova Source Expert Review Green was added to KAT5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ZNF335	Arina Puzriakova Source Expert Review Green was added to ZNF335. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ZIC1	Arina Puzriakova Source Expert Review Green was added to ZIC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SETD1A	Arina Puzriakova Source Expert Review Green was added to SETD1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PET100	Arina Puzriakova Source Expert Review Green was added to PET100. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NUDT2	Arina Puzriakova Source Expert Review Green was added to NUDT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MFSD2A	Arina Puzriakova Source Expert Review Green was added to MFSD2A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MAPRE2	Arina Puzriakova Source Expert Review Green was added to MAPRE2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CDH2	Arina Puzriakova Source Expert Review Green was added to CDH2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SMG8	Arina Puzriakova Source Expert Review Green was added to SMG8. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LSS	Arina Puzriakova Source Expert Review Green was added to LSS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KCNMA1	Arina Puzriakova Source Expert Review Green was added to KCNMA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	H3F3B	Arina Puzriakova Source Expert Review Green was added to H3F3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	H3F3A	Arina Puzriakova Source Expert Review Green was added to H3F3A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KDM4B	Arina Puzriakova Source Expert Review Green was added to KDM4B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	BICRA	Arina Puzriakova Source Expert Review Green was added to BICRA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ZFHX4	Arina Puzriakova Source Expert Review Green was added to ZFHX4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SHMT2	Arina Puzriakova Source Expert Review Green was added to SHMT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NARS	Arina Puzriakova Source Expert Review Green was added to NARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MORC2	Arina Puzriakova Source Expert Review Green was added to MORC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LARS	Arina Puzriakova Source Expert Review Green was added to LARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	POLR1C	Arina Puzriakova Source Expert Review Green was added to POLR1C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NUS1	Arina Puzriakova Source Expert Review Green was added to NUS1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PUM1	Arina Puzriakova Source Expert Review Green was added to PUM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RALGAPA1	Arina Puzriakova Source Expert Review Green was added to RALGAPA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RARS	Arina Puzriakova Source Expert Review Green was added to RARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CEP55	Arina Puzriakova Source Expert Review Green was added to CEP55. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CTU2	Arina Puzriakova Source Expert Review Green was added to CTU2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TRAPPC4	Arina Puzriakova Source Expert Review Green was added to TRAPPC4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	UGP2	Arina Puzriakova Source Expert Review Green was added to UGP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CXorf56	Arina Puzriakova Source Expert Review Green was added to CXorf56. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KAT8	Arina Puzriakova Source Expert Review Green was added to KAT8. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SLC5A6	Arina Puzriakova Source Expert Review Green was added to SLC5A6. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SNX27	Arina Puzriakova Source Expert Review Green was added to SNX27. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	WNT1	Arina Puzriakova Source Expert Review Green was added to WNT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	YIF1B	Arina Puzriakova Source Expert Review Green was added to YIF1B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	VARS2	Arina Puzriakova Source Expert Review Green was added to VARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	UGDH	Arina Puzriakova Source Expert Review Green was added to UGDH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TTC5	Arina Puzriakova Source Expert Review Green was added to TTC5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TRNT1	Arina Puzriakova Source Expert Review Green was added to TRNT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TNRC6B	Arina Puzriakova Source Expert Review Green was added to TNRC6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TET3	Arina Puzriakova Source Expert Review Green was added to TET3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TENM3	Arina Puzriakova Source Expert Review Green was added to TENM3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TASP1	Arina Puzriakova Source Expert Review Green was added to TASP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SUZ12	Arina Puzriakova Source Expert Review Green was added to SUZ12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SUPT16H	Arina Puzriakova Source Expert Review Green was added to SUPT16H. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SPTBN4	Arina Puzriakova Source Expert Review Green was added to SPTBN4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SPOP	Arina Puzriakova Source Expert Review Green was added to SPOP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SOX6	Arina Puzriakova Source Expert Review Green was added to SOX6. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SLC1A1	Arina Puzriakova Source Expert Review Green was added to SLC1A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SLC12A2	Arina Puzriakova Source Expert Review Green was added to SLC12A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SFXN4	Arina Puzriakova Source Expert Review Green was added to SFXN4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SBF1	Arina Puzriakova Source Expert Review Green was added to SBF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	SARS2	Arina Puzriakova Source Expert Review Green was added to SARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RSRC1	Arina Puzriakova Source Expert Review Green was added to RSRC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PPP1R12A	Arina Puzriakova Source Expert Review Green was added to PPP1R12A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIGS	Arina Puzriakova Source Expert Review Green was added to PIGS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIGK	Arina Puzriakova Source Expert Review Green was added to PIGK. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIBF1	Arina Puzriakova Source Expert Review Green was added to PIBF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PDHB	Arina Puzriakova Source Expert Review Green was added to PDHB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	OXR1	Arina Puzriakova Source Expert Review Green was added to OXR1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NRROS	Arina Puzriakova Source Expert Review Green was added to NRROS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NOVA2	Arina Puzriakova Source Expert Review Green was added to NOVA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NDUFA2	Arina Puzriakova Source Expert Review Green was added to NDUFA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MTHFS	Arina Puzriakova Source Expert Review Green was added to MTHFS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MN1	Arina Puzriakova Source Expert Review Green was added to MN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LYRM7	Arina Puzriakova Source Expert Review Green was added to LYRM7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	LIPT1	Arina Puzriakova Source Expert Review Green was added to LIPT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KLF7	Arina Puzriakova Source Expert Review Green was added to KLF7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KCNN3	Arina Puzriakova Source Expert Review Green was added to KCNN3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	HNRNPH1	Arina Puzriakova Source Expert Review Green was added to HNRNPH1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	GPC4	Arina Puzriakova Source Expert Review Green was added to GPC4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	GALNT2	Arina Puzriakova Source Expert Review Green was added to GALNT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	EIF2AK2	Arina Puzriakova Source Expert Review Green was added to EIF2AK2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	EARS2	Arina Puzriakova Source Expert Review Green was added to EARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	DNM1L	Arina Puzriakova Source Expert Review Green was added to DNM1L. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	DHX37	Arina Puzriakova Source Expert Review Green was added to DHX37. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CTNND1	Arina Puzriakova Source Expert Review Green was added to CTNND1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CNTNAP1	Arina Puzriakova Source Expert Review Green was added to CNTNAP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	B9D2	Arina Puzriakova Source Expert Review Green was added to B9D2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ATAD1	Arina Puzriakova Source Expert Review Green was added to ATAD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ADD3	Arina Puzriakova Source Expert Review Green was added to ADD3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ADARB1	Arina Puzriakova Source Expert Review Green was added to ADARB1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	DLL1	Arina Puzriakova Source Expert Review Green was added to DLL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RNF113A	Arina Puzriakova Source Expert Review Green was added to RNF113A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	GAD1	Arina Puzriakova Source Expert Review Green was added to GAD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ALG9	Arina Puzriakova Source Expert Review Green was added to ALG9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	STT3A	Arina Puzriakova Source Expert Review Green was added to STT3A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NEDD4L	Arina Puzriakova Source Expert Review Green was added to NEDD4L. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	MADD	Arina Puzriakova Source Expert Review Green was added to MADD. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	KDM6B	Arina Puzriakova Source Expert Review Green was added to KDM6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	HERC2	Arina Puzriakova Source Expert Review Green was added to HERC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CDK19	Arina Puzriakova Source Expert Review Green was added to CDK19. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	AHCY	Arina Puzriakova Source Expert Review Green was added to AHCY. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PIGP	Arina Puzriakova Source Expert Review Green was added to PIGP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RNF13	Arina Puzriakova Source Expert Review Green was added to RNF13. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	EXT2	Arina Puzriakova Source Expert Review Green was added to EXT2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PTRHD1	Arina Puzriakova Source Expert Review Green was added to PTRHD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	XYLT1	Arina Puzriakova Source Expert Review Green was added to XYLT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	WDFY3	Arina Puzriakova Source Expert Review Green was added to WDFY3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	USP7	Arina Puzriakova Source Expert Review Green was added to USP7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TRPM3	Arina Puzriakova Source Expert Review Green was added to TRPM3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	NR4A2	Arina Puzriakova Source Expert Review Green was added to NR4A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	CEP104	Arina Puzriakova Source Expert Review Green was added to CEP104. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	C2CD3	Arina Puzriakova Source Expert Review Green was added to C2CD3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ATP1A2	Arina Puzriakova Source Expert Review Green was added to ATP1A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ABAT	Arina Puzriakova Source Expert Review Green was added to ABAT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TCTN3	Arina Puzriakova Source Expert Review Green was added to TCTN3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TOR1A	Arina Puzriakova Source Expert Review Green was added to TOR1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	TANC2	Arina Puzriakova Source Expert Review Green was added to TANC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	ADAM22	Arina Puzriakova Source Expert Review Green was added to ADAM22. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	UBR7	Arina Puzriakova Source Expert Review Green was added to UBR7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	VPS4A	Arina Puzriakova Source Expert Review Green was added to VPS4A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	RNU7-1	Arina Puzriakova Source Expert Review Green was added to RNU7-1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	PPIL1	Arina Puzriakova Source Expert Review Green was added to PPIL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Intellectual disability v3.1509	FBRSL1	Arina Puzriakova Source Expert Review Green was added to FBRSL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Rare genetic inflammatory skin disorders v1.53	ECM1	Arina Puzriakova Tag Q4_21_rating was removed from gene: ECM1. Tag Q4_21_NHS_review was removed from gene: ECM1.
09 Mar 2022	Rare genetic inflammatory skin disorders v1.53	ECM1	Arina Puzriakova commented on gene: ECM1
09 Mar 2022	Rare genetic inflammatory skin disorders v1.52	ECM1	Arina Puzriakova Source Expert Review Green was added to ECM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.43	USP9X	Arina Puzriakova Tag Q4_21_rating was removed from gene: USP9X. Tag Q4_21_NHS_review was removed from gene: USP9X.
09 Mar 2022	Pigmentary skin disorders v1.43	TFE3	Arina Puzriakova Tag Q4_21_rating was removed from gene: TFE3. Tag Q4_21_NHS_review was removed from gene: TFE3.
09 Mar 2022	Pigmentary skin disorders v1.43	SMARCAL1	Arina Puzriakova Tag Q4_21_rating was removed from gene: SMARCAL1. Tag Q4_21_NHS_review was removed from gene: SMARCAL1.
09 Mar 2022	Pigmentary skin disorders v1.43	PHF6	Arina Puzriakova Tag Q4_21_rating was removed from gene: PHF6. Tag Q4_21_NHS_review was removed from gene: PHF6.
09 Mar 2022	Pigmentary skin disorders v1.43	NDUFB11	Arina Puzriakova Tag Q4_21_expert_review was removed from gene: NDUFB11. Tag Q4_21_NHS_review was removed from gene: NDUFB11.
09 Mar 2022	Pigmentary skin disorders v1.43	HCCS	Arina Puzriakova Tag Q4_21_rating was removed from gene: HCCS. Tag Q4_21_NHS_review was removed from gene: HCCS.
09 Mar 2022	Pigmentary skin disorders v1.43	FLNA	Arina Puzriakova Classified gene: FLNA as Amber List (moderate evidence)
09 Mar 2022	Pigmentary skin disorders v1.43	FLNA	Arina Puzriakova Gene: flna has been classified as Amber List (Moderate Evidence).
09 Mar 2022	Pigmentary skin disorders v1.42	FLNA	Arina Puzriakova Tag Q3_21_expert_review was removed from gene: FLNA.
09 Mar 2022	Pigmentary skin disorders v1.42	DDX3X	Arina Puzriakova Tag Q4_21_rating was removed from gene: DDX3X. Tag Q4_21_NHS_review was removed from gene: DDX3X.
09 Mar 2022	Pigmentary skin disorders v1.42	COX7B	Arina Puzriakova Tag Q4_21_rating was removed from gene: COX7B. Tag Q4_21_NHS_review was removed from gene: COX7B.
09 Mar 2022	Pigmentary skin disorders v1.42	USP9X	Arina Puzriakova commented on gene: USP9X
09 Mar 2022	Pigmentary skin disorders v1.42	TFE3	Arina Puzriakova commented on gene: TFE3
09 Mar 2022	Pigmentary skin disorders v1.42	SMARCAL1	Arina Puzriakova commented on gene: SMARCAL1
09 Mar 2022	Pigmentary skin disorders v1.42	PHF6	Arina Puzriakova commented on gene: PHF6
09 Mar 2022	Pigmentary skin disorders v1.42	NDUFB11	Arina Puzriakova commented on gene: NDUFB11
09 Mar 2022	Pigmentary skin disorders v1.42	HCCS	Arina Puzriakova commented on gene: HCCS
09 Mar 2022	Pigmentary skin disorders v1.42	FLNA	Arina Puzriakova commented on gene: FLNA: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. It has been agreed that this gene should remain amber at this time.
09 Mar 2022	Pigmentary skin disorders v1.42	DDX3X	Arina Puzriakova commented on gene: DDX3X
09 Mar 2022	Pigmentary skin disorders v1.42	COX7B	Arina Puzriakova commented on gene: COX7B
09 Mar 2022	Pigmentary skin disorders v1.41	USP9X	Arina Puzriakova Source Expert Review Green was added to USP9X. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	TFE3	Arina Puzriakova Source Expert Review Green was added to TFE3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	SMARCAL1	Arina Puzriakova Source Expert Review Green was added to SMARCAL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	PHF6	Arina Puzriakova Source Expert Review Green was added to PHF6. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	HCCS	Arina Puzriakova Source Expert Review Green was added to HCCS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	DDX3X	Arina Puzriakova Source Expert Review Green was added to DDX3X. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Pigmentary skin disorders v1.41	COX7B	Arina Puzriakova Source Expert Review Green was added to COX7B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	PTPN11	Arina Puzriakova Tag Q4_21_rating was removed from gene: PTPN11. Tag Q4_21_NHS_review was removed from gene: PTPN11.
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	PORCN	Arina Puzriakova Tag Q4_21_rating was removed from gene: PORCN. Tag Q4_21_NHS_review was removed from gene: PORCN.
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	BRAF	Arina Puzriakova Tag Q4_21_rating was removed from gene: BRAF. Tag Q4_21_NHS_review was removed from gene: BRAF.
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	PTPN11	Arina Puzriakova commented on gene: PTPN11
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	PORCN	Arina Puzriakova commented on gene: PORCN
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.22	BRAF	Arina Puzriakova commented on gene: BRAF
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.21	PTPN11	Arina Puzriakova Source Expert Review Green was added to PTPN11. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.21	PORCN	Arina Puzriakova Source Expert Review Green was added to PORCN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Mosaic skin disorders - deep sequencing v1.21	BRAF	Arina Puzriakova Source Expert Review Green was added to BRAF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
09 Mar 2022	Adult onset leukodystrophy v1.40	LIG3	Eleanor Williams Tag Q2_21_rating was removed from gene: LIG3.
09 Mar 2022	Adult onset leukodystrophy v1.40	EPRS	Eleanor Williams Tag Q2_21_rating was removed from gene: EPRS.
09 Mar 2022	Adult onset leukodystrophy v1.40	EARS2	Eleanor Williams Tag Q4_21_expert_review was removed from gene: EARS2.
09 Mar 2022	Adult onset leukodystrophy v1.40	CYP7B1	Eleanor Williams Tag Q2_21_expert_review was removed from gene: CYP7B1.
09 Mar 2022	Adult onset leukodystrophy v1.40	CTC1	Eleanor Williams Tag Q3_21_expert_review was removed from gene: CTC1.
09 Mar 2022	Adult onset leukodystrophy v1.40	AUH	Eleanor Williams Tag Q2_21_rating was removed from gene: AUH.
09 Mar 2022	Adult onset leukodystrophy v1.40	LIG3	Sarah Leigh commented on gene: LIG3
09 Mar 2022	Adult onset leukodystrophy v1.40	EPRS	Sarah Leigh commented on gene: EPRS

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