{"count":221416,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=484","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=482","results":[{"created":"2024-03-07T11:53:00.801254+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1587","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SLC12A9 as Green List (high evidence)","entity_name":"SLC12A9","entity_type":"gene"},{"created":"2024-03-07T11:53:00.788642+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1587","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc12a9 has been classified as Green List (High Evidence).","entity_name":"SLC12A9","entity_type":"gene"},{"created":"2024-03-07T11:52:58.465812+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5715","user_name":"Elena Savva","item_type":"entity","text":"Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:52:44.071293+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2330","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Amber List (moderate evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:52:44.025425+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2330","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Amber List (Moderate Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:52:25.469305+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5715","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: POP1 were set to ","entity_name":"POP1","entity_type":"gene"},{"created":"2024-03-07T11:52:21.222672+11:00","panel_name":"Hypertrophic cardiomyopathy_HCM","panel_id":111,"panel_version":"0.177","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: CORIN as ready","entity_name":"CORIN","entity_type":"gene"},{"created":"2024-03-07T11:52:21.203469+11:00","panel_name":"Hypertrophic cardiomyopathy_HCM","panel_id":111,"panel_version":"0.177","user_name":"Seb Lunke","item_type":"entity","text":"Gene: corin has been classified as Red List (Low Evidence).","entity_name":"CORIN","entity_type":"gene"},{"created":"2024-03-07T11:51:40.298171+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1586","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: SNF8 as ready","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:40.285326+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1586","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:31.933059+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1586","user_name":"Zornitza Stark","item_type":"entity","text":"gene: SLC12A9 was added\ngene: SLC12A9 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC12A9 were set to 38334070\nPhenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related\nReview for gene: SLC12A9 was set to GREEN\nAdded comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopment phenotype, skeletal and brain abnormalities, hypopigmentation, dysmorphic features. \nSources: Literature","entity_name":"SLC12A9","entity_type":"gene"},{"created":"2024-03-07T11:51:29.049452+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.518","user_name":"Elena Savva","item_type":"entity","text":"Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:24.080057+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1586","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Green List (high evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:24.000522+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1586","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:07.698361+11:00","panel_name":"Hypertrophic cardiomyopathy_HCM","panel_id":111,"panel_version":"0.177","user_name":"Seb Lunke","item_type":"entity","text":"Classified gene: CORIN as Red List (low evidence)","entity_name":"CORIN","entity_type":"gene"},{"created":"2024-03-07T11:51:07.587660+11:00","panel_name":"Hypertrophic cardiomyopathy_HCM","panel_id":111,"panel_version":"0.177","user_name":"Seb Lunke","item_type":"entity","text":"Gene: corin has been classified as Red List (Low Evidence).","entity_name":"CORIN","entity_type":"gene"},{"created":"2024-03-07T11:51:07.458340+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.517","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Green List (high evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:51:07.377846+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.517","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:50:46.771362+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.517","user_name":"Elena Savva","item_type":"entity","text":"Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:50:37.652023+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Classified gene: TUBA4A as Amber List (moderate evidence)","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:50:37.618868+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Gene: tuba4a has been classified as Amber List (Moderate Evidence).","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:50:33.570538+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5714","user_name":"Zornitza Stark","item_type":"entity","text":"gene: SLC12A9 was added\ngene: SLC12A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC12A9 were set to 38334070\nPhenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related\nReview for gene: SLC12A9 was set to GREEN\nAdded comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopmental phenotype, skeletal abnormalities, brain abnormalities, hypopigmentation, dysmorphic features. \nSources: Literature","entity_name":"SLC12A9","entity_type":"gene"},{"created":"2024-03-07T11:50:33.511541+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2329","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Amber List (moderate evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:50:33.470810+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2329","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Amber List (Moderate Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:49:50.142616+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.517","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Green List (high evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:49:50.056738+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.517","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:49:08.599655+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: TUBA4A as ready","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:49:08.584070+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Gene: tuba4a has been classified as Amber List (Moderate Evidence).","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:48:47.644620+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Classified gene: TUBA4A as Amber List (moderate evidence)","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:48:47.564275+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.12","user_name":"Seb Lunke","item_type":"entity","text":"Gene: tuba4a has been classified as Amber List (Moderate Evidence).","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:48:40.446077+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.516","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: SNF8 as ready","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:40.428432+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.516","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been removed from the panel.","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:37.364247+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5714","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: SNF8 as ready","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:37.341346+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5714","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:10.918520+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5714","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Green List (high evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:10.896726+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5714","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Green List (High Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:10.449921+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2329","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Amber List (moderate evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:48:10.362135+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2329","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Amber List (Moderate Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:47:48.435751+11:00","panel_name":"Optic Atrophy","panel_id":149,"panel_version":"1.30","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: SNF8 as ready","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:47:48.353460+11:00","panel_name":"Optic Atrophy","panel_id":149,"panel_version":"1.30","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Amber List (Moderate Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:47:46.568284+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1585","user_name":"Chern Lim","item_type":"entity","text":"gene: SNF8 was added\ngene: SNF8 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNF8 were set to 38423010\nPhenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related\nReview for gene: SNF8 was set to GREEN\ngene: SNF8 was marked as current diagnostic\nAdded comment: PMID: 38423010\r\n- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.\r\n- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.\r\n- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. \nSources: Literature","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:47:42.282206+11:00","panel_name":"Aortopathy_Connective Tissue Disorders","panel_id":44,"panel_version":"1.80","user_name":"Chris Ciotta","item_type":"entity","text":"changed review comment from: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency. \r\n\r\nThis individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.\r\n\r\nNo other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.\r\n\r\nMouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice. \nSources: Literature; to: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency. \r\n\r\nThis individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.\r\n\r\nNo other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.\r\n\r\nMouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice. \r\nSources: Literature","entity_name":"THBS2","entity_type":"gene"},{"created":"2024-03-07T11:47:22.401297+11:00","panel_name":"Optic Atrophy","panel_id":149,"panel_version":"1.30","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: SNF8 as Amber List (moderate evidence)","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:47:22.390807+11:00","panel_name":"Optic Atrophy","panel_id":149,"panel_version":"1.30","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been classified as Amber List (Moderate Evidence).","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:46:54.095772+11:00","panel_name":"Aortopathy_Connective Tissue Disorders","panel_id":44,"panel_version":"1.80","user_name":"Chris Ciotta","item_type":"entity","text":"gene: THBS2 was added\ngene: THBS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: THBS2 were set to PMID: 38433265\nPhenotypes for gene: THBS2 were set to Ehlers-Danlos syndrome\nPenetrance for gene: THBS2 were set to Complete\nReview for gene: THBS2 was set to AMBER\nAdded comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency. \r\n\r\nThis individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.\r\n\r\nNo other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.\r\n\r\nMouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice. \nSources: Literature","entity_name":"THBS2","entity_type":"gene"},{"created":"2024-03-07T11:46:47.142778+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2328","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: SNF8 as ready","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:46:47.062943+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2328","user_name":"Elena Savva","item_type":"entity","text":"Gene: snf8 has been removed from the panel.","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:46:32.676001+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.200","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:46:30.137754+11:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.272","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:46:23.882834+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1585","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: TUBA4A as ready","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:46:23.871259+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1585","user_name":"Seb Lunke","item_type":"entity","text":"Gene: tuba4a has been classified as Amber List (Moderate Evidence).","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:46:22.777472+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.199","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: HSPG2 were set to ","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:46:12.164893+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1585","user_name":"Seb Lunke","item_type":"entity","text":"Classified gene: TUBA4A as Amber List (moderate evidence)","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:46:12.151976+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1585","user_name":"Seb Lunke","item_type":"entity","text":"Gene: tuba4a has been classified as Amber List (Moderate Evidence).","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:46:03.734189+11:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.272","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: HSPG2 were set to ","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:45:36.725882+11:00","panel_name":"Skeletal Dysplasia_Fetal","panel_id":28,"panel_version":"0.219","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: HSPG2 were set to ","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:44:08.228231+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.198","user_name":"Dean Phelan","item_type":"entity","text":"reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:43:19.376905+11:00","panel_name":"Optic Atrophy","panel_id":149,"panel_version":"1.29","user_name":"Chern Lim","item_type":"entity","text":"gene: SNF8 was added\ngene: SNF8 was added to Optic Atrophy. Sources: Literature\nMode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNF8 were set to 38423010\nPhenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related\nReview for gene: SNF8 was set to AMBER\ngene: SNF8 was marked as current diagnostic\nAdded comment: PMID: 38423010\r\n- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.\r\n- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.\r\n- Three of the patients (from two families) with the milder phenotype also have optic atrophy.\r\n\r\n- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. \nSources: Literature","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:42:41.557079+11:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.271","user_name":"Dean Phelan","item_type":"entity","text":"reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:41:21.985728+11:00","panel_name":"Skeletal Dysplasia_Fetal","panel_id":28,"panel_version":"0.218","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: HSPG2 were changed from  to Schwartz-Jampel syndrome, type 1, MIM#255800; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139)","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:40:51.291715+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.2328","user_name":"Chern Lim","item_type":"entity","text":"gene: SNF8 was added\ngene: SNF8 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNF8 were set to 38423010\nPhenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related\nReview for gene: SNF8 was set to AMBER\ngene: SNF8 was marked as current diagnostic\nAdded comment: PMID: 38423010\r\n- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.\r\n- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.\r\n- Two of the patients also had seizures.\r\n\r\n- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. \nSources: Literature","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:40:49.729789+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Dean Phelan","item_type":"entity","text":"reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:40:46.630882+11:00","panel_name":"Hypertrophic cardiomyopathy_HCM","panel_id":111,"panel_version":"0.176","user_name":"Daniel Flanagan","item_type":"entity","text":"gene: CORIN was added\ngene: CORIN was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list\nMode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CORIN were set to 37913506; 15637153\nPhenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)\nReview for gene: CORIN was set to RED\nAdded comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin. \r\n\r\nOne sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar. \r\n\r\nCor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension. \nSources: Expert list","entity_name":"CORIN","entity_type":"gene"},{"created":"2024-03-07T11:39:18.136941+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Suliman Khan","item_type":"entity","text":"gene: SNUPN was added\ngene: SNUPN was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623\nPhenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152\nReview for gene: SNUPN was set to GREEN\nAdded comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.\r\n\r\nPMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy. \nSources: Literature","entity_name":"SNUPN","entity_type":"gene"},{"created":"2024-03-07T11:39:15.780289+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Lucy Spencer","item_type":"entity","text":"gene: APOLD1 was added\ngene: APOLD1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: APOLD1 were set to 35638551\nPhenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)\nReview for gene: APOLD1 was set to AMBER\nAdded comment: PMID: 35638551\r\n1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.  \r\n\r\nThis gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein\r\n\r\nInterestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.\r\n\r\nImmunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. \nSources: Literature","entity_name":"APOLD1","entity_type":"gene"},{"created":"2024-03-07T11:38:22.121121+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.516","user_name":"Chern Lim","item_type":"entity","text":"edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:38:11.135679+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5713","user_name":"Chern Lim","item_type":"entity","text":"edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:37:26.174783+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: RGS6 as ready","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:37:26.164551+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Seb Lunke","item_type":"entity","text":"Gene: rgs6 has been classified as Red List (Low Evidence).","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:37:16.679685+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1584","user_name":"Seb Lunke","item_type":"entity","text":"gene: RGS6 was added\ngene: RGS6 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RGS6 were set to 38332109; 25525169\nPhenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149\nReview for gene: RGS6 was set to RED\nAdded comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice. \nSources: Literature","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:37:11.183467+11:00","panel_name":"Bleeding and Platelet Disorders","panel_id":54,"panel_version":"1.27","user_name":"Lucy Spencer","item_type":"entity","text":"gene: APOLD1 was added\ngene: APOLD1 was added to Bleeding and Platelet Disorders. Sources: Literature\nMode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: APOLD1 were set to 35638551\nPhenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)\nReview for gene: APOLD1 was set to AMBER\nAdded comment: PMID: 35638551\r\n1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.  \r\n\r\nThis gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein\r\n\r\nInterestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.\r\n\r\nImmunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. \nSources: Literature","entity_name":"APOLD1","entity_type":"gene"},{"created":"2024-03-07T11:36:35.200154+11:00","panel_name":"Skeletal Dysplasia_Fetal","panel_id":28,"panel_version":"0.217","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: HSPG2 as ready","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:36:35.186371+11:00","panel_name":"Skeletal Dysplasia_Fetal","panel_id":28,"panel_version":"0.217","user_name":"Ain Roesley","item_type":"entity","text":"Gene: hspg2 has been classified as Green List (High Evidence).","entity_name":"HSPG2","entity_type":"gene"},{"created":"2024-03-07T11:36:22.976531+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5713","user_name":"Melanie Marty","item_type":"entity","text":"gene: DIP2C was added\ngene: DIP2C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: DIP2C were set to PMID: 38421105\nPhenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related\nReview for gene: DIP2C was set to GREEN\nAdded comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).  \r\nAll patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve) \nSources: Literature","entity_name":"DIP2C","entity_type":"gene"},{"created":"2024-03-07T11:35:52.773199+11:00","panel_name":"Cataract","panel_id":66,"panel_version":"0.362","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: RGS6 as ready","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:35:52.761447+11:00","panel_name":"Cataract","panel_id":66,"panel_version":"0.362","user_name":"Seb Lunke","item_type":"entity","text":"Gene: rgs6 has been classified as Red List (Low Evidence).","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:35:49.455673+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Naomi Baker","item_type":"entity","text":"gene: TOGARAM2 was added\ngene: TOGARAM2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TOGARAM2 were set to PMID:38374469\nPhenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related\nReview for gene: TOGARAM2 was set to RED\nAdded comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells. \nSources: Literature","entity_name":"TOGARAM2","entity_type":"gene"},{"created":"2024-03-07T11:34:53.067374+11:00","panel_name":"Cataract","panel_id":66,"panel_version":"0.362","user_name":"Seb Lunke","item_type":"entity","text":"gene: RGS6 was added\ngene: RGS6 was added to Cataract. Sources: Literature\nMode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RGS6 were set to 38332109; 25525169\nPhenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149\nReview for gene: RGS6 was set to RED\nAdded comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice. \nSources: Literature","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:34:46.177346+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.11","user_name":"Suliman Khan","item_type":"entity","text":"gene: SNUPN was added\ngene: SNUPN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature\nMode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623\nPhenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152\nPenetrance for gene: SNUPN were set to unknown\nAdded comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.\r\n\r\nPMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy. \nSources: Literature","entity_name":"SNUPN","entity_type":"gene"},{"created":"2024-03-07T11:33:54.829093+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Melanie Marty","item_type":"entity","text":"gene: DIP2C was added\ngene: DIP2C was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: DIP2C were set to PMID: 38421105\nPhenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related\nReview for gene: DIP2C was set to GREEN\nAdded comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).  \r\nAll patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve) \nSources: Literature","entity_name":"DIP2C","entity_type":"gene"},{"created":"2024-03-07T11:32:57.155844+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.249","user_name":"Seb Lunke","item_type":"entity","text":"Marked gene: RGS6 as ready","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:32:57.143929+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.249","user_name":"Seb Lunke","item_type":"entity","text":"Gene: rgs6 has been classified as Red List (Low Evidence).","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:32:51.197175+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5713","user_name":"Elena Savva","item_type":"entity","text":"Publications for gene: DENND5B were set to ","entity_name":"DENND5B","entity_type":"gene"},{"created":"2024-03-07T11:32:47.420904+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.249","user_name":"Seb Lunke","item_type":"entity","text":"gene: RGS6 was added\ngene: RGS6 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RGS6 were set to 38332109; 25525169\nPhenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149\nReview for gene: RGS6 was set to RED\nAdded comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice. \nSources: Literature","entity_name":"RGS6","entity_type":"gene"},{"created":"2024-03-07T11:32:28.693765+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5713","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: DENND5B was changed from None to None","entity_name":"DENND5B","entity_type":"gene"},{"created":"2024-03-07T11:32:01.701704+11:00","panel_name":"Leukodystrophy - paediatric","panel_id":298,"panel_version":"0.306","user_name":"Elena Savva","item_type":"entity","text":"Publications for gene: DENND5B were set to ","entity_name":"DENND5B","entity_type":"gene"},{"created":"2024-03-07T11:30:58.389918+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: NIT1 as ready","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:58.378169+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Ain Roesley","item_type":"entity","text":"Gene: nit1 has been classified as Green List (High Evidence).","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:52.081685+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NIT1 as ready","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:52.068361+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nit1 has been classified as Green List (High Evidence).","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:48.970288+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: NIT1 as Green List (high evidence)","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:48.944818+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1583","user_name":"Ain Roesley","item_type":"entity","text":"Gene: nit1 has been classified as Green List (High Evidence).","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:43.258112+11:00","panel_name":"Limb-Girdle Muscular Dystrophy and Distal Myopathy","panel_id":3071,"panel_version":"1.26","user_name":"Suliman Khan","item_type":"entity","text":"gene: SNUPN was added\ngene: SNUPN was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature\nMode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623\nPhenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152\nPenetrance for gene: SNUPN were set to unknown\nReview for gene: SNUPN was set to GREEN\nAdded comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.\r\n\r\nPMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy. \nSources: Literature","entity_name":"SNUPN","entity_type":"gene"},{"created":"2024-03-07T11:30:42.797670+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1582","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NIT1 as Green List (high evidence)","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:42.789766+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1582","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nit1 has been classified as Green List (High Evidence).","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:30:14.841214+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.516","user_name":"Chern Lim","item_type":"entity","text":"gene: SNF8 was added\ngene: SNF8 was added to Callosome. Sources: Literature\nMode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNF8 were set to 38423010\nPhenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia\nReview for gene: SNF8 was set to GREEN\ngene: SNF8 was marked as current diagnostic\nAdded comment: PMID: 38423010\r\n-\tNine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.\r\n-\tThe phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.\r\n-\tFunctional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. \nSources: Literature","entity_name":"SNF8","entity_type":"gene"},{"created":"2024-03-07T11:29:15.608247+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1581","user_name":"Paul De Fazio","item_type":"entity","text":"edited their review of gene: NIT1: Changed rating: GREEN","entity_name":"NIT1","entity_type":"gene"},{"created":"2024-03-07T11:29:02.884611+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1581","user_name":"Sarah Pantaleo","item_type":"entity","text":"gene: TUBA4A was added\ngene: TUBA4A was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: TUBA4A were set to PMID: 38413182\nPhenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952\nReview for gene: TUBA4A was set to AMBER\nAdded comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy. \r\n\r\nIdentified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.\r\n\r\nThe variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model. \r\n\r\nPatient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.\r\n\r\nPatient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.\r\n\r\nNo likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification. \nSources: Literature","entity_name":"TUBA4A","entity_type":"gene"},{"created":"2024-03-07T11:28:55.857927+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1581","user_name":"Elena Savva","item_type":"entity","text":"Publications for gene: DENND5B were set to ","entity_name":"DENND5B","entity_type":"gene"},{"created":"2024-03-07T11:28:49.102004+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5712","user_name":"Chern Lim","item_type":"entity","text":"gene: SNF8 was added\ngene: SNF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SNF8 were set to 38423010\nPhenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia\nReview for gene: SNF8 was set to GREEN\ngene: SNF8 was marked as current diagnostic\nAdded comment: PMID: 38423010\r\n-\tNine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.\r\n-\tThe phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.\r\n-\tFunctional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. \nSources: Literature","entity_name":"SNF8","entity_type":"gene"}]}