{"count":220309,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=891","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=889","results":[{"created":"2022-04-07T11:54:04.316123+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12729","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TTC21B were changed from Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome; Glomerular disorder MONDO:0019722, TTC21B-related","entity_name":"TTC21B","entity_type":"gene"},{"created":"2022-04-07T11:53:59.575119+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4658","user_name":"Daniel Flanagan","item_type":"entity","text":"changed review comment from: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance.  9 missense and 3 nonsense. Supporting functional analysis for missense. \nSources: Expert list; to: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), dissimilar forms of seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance.  9 missense and 3 nonsense. Supporting functional analysis for missense. \r\nSources: Expert list","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:53:54.281610+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1540","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: CACNA2D1 as Green List (high evidence)","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:53:54.276459+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1540","user_name":"Alison Yeung","item_type":"entity","text":"Added comment: Comment on list classification: Two affected individuals with very similar and specific phenotypes. Functional studies in patient cells showed reduced protein expression. Two variants are frameshift, one missense variant shown to affect channel function.","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:53:54.237145+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1540","user_name":"Alison Yeung","item_type":"entity","text":"Gene: cacna2d1 has been classified as Green List (High Evidence).","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:52:43.094286+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12728","user_name":"Belinda Chong","item_type":"entity","text":"reviewed gene: RSPO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29769720, 32457899; Phenotypes: Tetraamelia syndrome 2, MIM# 618021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"RSPO2","entity_type":"gene"},{"created":"2022-04-07T11:52:09.012070+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1539","user_name":"Daniel Flanagan","item_type":"entity","text":"gene: ATP2B1 was added\ngene: ATP2B1 was added to Genetic Epilepsy. Sources: Expert list\nMode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: ATP2B1 were set to PMID: 35358416\nPhenotypes for gene: ATP2B1 were set to Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related\nReview for gene: ATP2B1 was set to GREEN\nAdded comment: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), dissimilar forms of seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance. 9 missense and 3 nonsense reported. Supporting functional analysis for missense. \nSources: Expert list","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:50:31.545446+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4658","user_name":"Naomi Baker","item_type":"entity","text":"gene: TRAPPC10 was added\ngene: TRAPPC10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: TRAPPC10 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRAPPC10 were set to PMID: 35298461; 30167849\nPhenotypes for gene: TRAPPC10 were set to neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related\nReview for gene: TRAPPC10 was set to GREEN\nAdded comment: PMID: 35298461 – two Pakistani families reported with homozygous variants.  Family 1 has frameshift variant in 8 affected individual and family 2 has missense variant in 2 affected individuals. Patients present with microcephaly, short stature, hypotonia, severe ID and behavioural abnormalities.  Seizures also reported in 4/10 individuals. Paper also reported brain abnormalities in null mouse model and other functional in transfected cell lines.\r\n\r\nPMID: 30167849 – initial report of family 2 above. \nSources: Literature","entity_name":"TRAPPC10","entity_type":"gene"},{"created":"2022-04-07T11:48:37.126213+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12728","user_name":"Naomi Baker","item_type":"entity","text":"gene: TRAPPC10 was added\ngene: TRAPPC10 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TRAPPC10 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRAPPC10 were set to PMID: 35298461; 30167849\nPhenotypes for gene: TRAPPC10 were set to neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related\nReview for gene: TRAPPC10 was set to GREEN\nAdded comment: PMID: 35298461 – two Pakistani families reported with homozygous variants.  Family 1 has frameshift variant in 8 affected individual and family 2 has missense variant in 2 affected individuals. Patients present with microcephaly, short stature, hypotonia, severe ID and behavioural abnormalities.  Seizures also reported in 4/10 individuals. Paper also reported brain abnormalities in null mouse model and other functional in transfected cell lines.\r\n\r\nPMID: 30167849 – initial report of family 2 above. \nSources: Literature","entity_name":"TRAPPC10","entity_type":"gene"},{"created":"2022-04-07T11:48:26.982671+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12728","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FUZ were changed from {Neural tube defects, susceptibility to}\tMIM#182940 to {Neural tube defects, susceptibility to}\tMIM#182940; craniosynostosis, FUZ-related MONDO#0015469","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:48:05.366280+10:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"1.47","user_name":"Alison Yeung","item_type":"entity","text":"Marked gene: ADAM22 as ready","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:48:05.348101+10:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"1.47","user_name":"Alison Yeung","item_type":"entity","text":"Gene: adam22 has been classified as Green List (High Evidence).","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:48:03.196895+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12727","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: FUZ was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:47:55.707779+10:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"1.47","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: ADAM22 as Green List (high evidence)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:47:55.698476+10:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"1.47","user_name":"Alison Yeung","item_type":"entity","text":"Gene: adam22 has been classified as Green List (High Evidence).","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:47:50.711216+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Paul De Fazio","item_type":"entity","text":"reviewed gene: ATP11A: Rating: AMBER; Mode of pathogenicity: None; Publications: 35278131; Phenotypes: Deafness, autosomal dominant 84 MIM#619810; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes","entity_name":"ATP11A","entity_type":"gene"},{"created":"2022-04-07T11:47:11.678477+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1539","user_name":"Michelle Torres","item_type":"entity","text":"changed review comment from: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.\r\n\r\nPatient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts.\r\n\r\nPatient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Functional of the p.(Gly209Asp) showed it affects channel function due to impaired localisation. \nSources: Literature; to: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.\r\n\r\nPatient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts.\r\n\r\nPatient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Mutagenesis of the p.(Gly209Asp) showed it affects channel function due to impaired localisation. \r\nSources: Literature","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:47:10.756489+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4658","user_name":"Daniel Flanagan","item_type":"entity","text":"gene: ATP2B1 was added\ngene: ATP2B1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list\nMode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: ATP2B1 were set to PMID: 35358416\nPhenotypes for gene: ATP2B1 were set to Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related\nReview for gene: ATP2B1 was set to GREEN\nAdded comment: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance.  9 missense and 3 nonsense. Supporting functional analysis for missense. \nSources: Expert list","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:47:05.084875+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4658","user_name":"Alison Yeung","item_type":"entity","text":"Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM#\t617933 to Developmental and epileptic encephalopathy 61 (MIM#617933)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:46:38.181612+10:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.117","user_name":"Naomi Baker","item_type":"entity","text":"gene: TRAPPC10 was added\ngene: TRAPPC10 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: TRAPPC10 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRAPPC10 were set to PMID: 35298461; 30167849\nPhenotypes for gene: TRAPPC10 were set to neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related\nReview for gene: TRAPPC10 was set to GREEN\nAdded comment: PMID: 35298461 – two Pakistani families reported with homozygous variants.  Family 1 has frameshift variant in 8 affected individual and family 2 has missense variant in 2 affected individuals. Patients present with microcephaly, short stature, hypotonia, severe ID and behavioural abnormalities.  Seizures also reported in 4/10 individuals. Paper also reported brain abnormalities in null mouse model and other functional in transfected cell lines.\r\nPMID: 30167849 – initial report of family 2 above. \nSources: Literature","entity_name":"TRAPPC10","entity_type":"gene"},{"created":"2022-04-07T11:46:23.383200+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4657","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: ADAM22 as Green List (high evidence)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:46:23.371709+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4657","user_name":"Alison Yeung","item_type":"entity","text":"Gene: adam22 has been classified as Green List (High Evidence).","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:45:40.377369+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1539","user_name":"Alison Yeung","item_type":"entity","text":"Phenotypes for gene: ADAM22 were changed from Developmental and epileptic encephalopathy 61 (MIM#617933) to Developmental and epileptic encephalopathy 61 (MIM#617933)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:45:13.920901+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.15","user_name":"Belinda Chong","item_type":"entity","text":"gene: MDFIC was added\ngene: MDFIC was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MDFIC were set to 35235341\nPhenotypes for gene: MDFIC were set to Hydrops fetalis MONDO:0015193\nReview for gene: MDFIC was set to GREEN\nAdded comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. \r\n\r\nSeven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax. \nSources: Literature","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:45:04.605859+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1538","user_name":"Alison Yeung","item_type":"entity","text":"Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM#\t617933 to Developmental and epileptic encephalopathy 61 (MIM#617933)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:45:02.264040+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Anna Ritchie","item_type":"entity","text":"reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: craniosynostosis, FUZ-related MONDO#0015469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:44:35.369754+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Belinda Chong","item_type":"entity","text":"edited their review of gene: MDFIC: Changed phenotypes: Hydrops fetalis MONDO:0015193","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:44:16.705001+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TNNI1 as ready","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:44:16.695860+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:44:15.685190+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1537","user_name":"Alison Yeung","item_type":"entity","text":"Publications for gene: ADAM22 were set to 27066583; 30237576","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:44:03.404986+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TNNI1 as Amber List (moderate evidence)","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:44:03.396054+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12726","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:43:39.130595+10:00","panel_name":"Hydrops fetalis","panel_id":116,"panel_version":"0.244","user_name":"Belinda Chong","item_type":"entity","text":"gene: MDFIC was added\ngene: MDFIC was added to Hydrops fetalis. Sources: Literature\nMode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MDFIC were set to 35235341\nPhenotypes for gene: MDFIC were set to Hydrops fetalis MONDO:0015193\nAdded comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. \r\n\r\nSeven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax. \nSources: Literature","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:43:37.976438+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12725","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:43:33.439561+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1536","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: ADAM22 as Green List (high evidence)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:43:33.430550+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1536","user_name":"Alison Yeung","item_type":"entity","text":"Gene: adam22 has been classified as Green List (High Evidence).","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:42:50.105127+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TNNI1 as ready","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:42:50.094468+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:42:45.549541+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TNNI1 as Amber List (moderate evidence)","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:42:45.535270+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:42:13.061632+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:42:11.865067+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12724","user_name":"Alison Yeung","item_type":"entity","text":"Marked gene: SLC35B2 as ready","entity_name":"SLC35B2","entity_type":"gene"},{"created":"2022-04-07T11:42:11.850830+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12724","user_name":"Alison Yeung","item_type":"entity","text":"Gene: slc35b2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC35B2","entity_type":"gene"},{"created":"2022-04-07T11:41:07.363566+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12724","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: SLC35B2 as Amber List (moderate evidence)","entity_name":"SLC35B2","entity_type":"gene"},{"created":"2022-04-07T11:41:07.346162+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12724","user_name":"Alison Yeung","item_type":"entity","text":"Gene: slc35b2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC35B2","entity_type":"gene"},{"created":"2022-04-07T11:40:01.693624+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.15","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TNNI1 as ready","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:40:01.662018+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.15","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:39:55.468246+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.15","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TNNI1 as Amber List (moderate evidence)","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:39:55.459671+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.15","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tnni1 has been classified as Amber List (Moderate Evidence).","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:39:53.196716+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Anna Ritchie","item_type":"entity","text":"Deleted their review","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:39:42.768304+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.14","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:37:53.926770+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Anna Ritchie","item_type":"entity","text":"commented on gene: FUZ","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:37:29.771085+10:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"1.46","user_name":"Lucy Spencer","item_type":"entity","text":"gene: ADAM22 was added\ngene: ADAM22 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature\nMode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ADAM22 were set to 35373813\nPhenotypes for gene: ADAM22 were set to Developmental and epileptic encephalopathy 61 (MIM#617933)\nReview for gene: ADAM22 was set to GREEN\nAdded comment: 19 additional patients (some related) all with compound het or homozygous ADAM22 variants. Including the previously described cases there are now 16 families with biallelic ADAM22 variants causing developmental epileptic encephalopathy.  All had infantile onset epilepsy and moderate to profound global dev delay and ID. Cerebellar atrophy on MRI and hypotonia were seen in over half of the individuals. \r\n\r\nFunctional studies suggest LOF- reduced protein expression/protein retained in ER and reduced cell surface expression. Variants described are a mix of missense and PTC. \nSources: Literature","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:37:01.419802+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ATP2B1 as ready","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:37:01.408405+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: atp2b1 has been classified as Green List (High Evidence).","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:36:47.632512+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ATP2B1 as Green List (high evidence)","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:36:47.615855+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12723","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: atp2b1 has been classified as Green List (High Evidence).","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:36:37.188599+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12722","user_name":"Anna Ritchie","item_type":"entity","text":"Deleted their review","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:36:30.144532+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12722","user_name":"Melanie Marty","item_type":"entity","text":"changed review comment from: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.\r\n\r\nFunctional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein. \nSources: Literature; to: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.\r\n\r\nFunctional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein. \r\nSources: Literature","entity_name":"SLC35B2","entity_type":"gene"},{"created":"2022-04-07T11:36:21.963419+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12722","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ATP2B1 were changed from Neurodevelopmental delay; autism; seizures; distal limb abnormalities to Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related","entity_name":"ATP2B1","entity_type":"gene"},{"created":"2022-04-07T11:36:04.730488+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4656","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: 35373813; Phenotypes: Developmental and epileptic encephalopathy 61 (MIM#617933); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:35:31.882742+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1535","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: 35373813; Phenotypes: Developmental and epileptic encephalopathy 61 (MIM#617933); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:34:06.645662+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12721","user_name":"Alison Yeung","item_type":"entity","text":"Phenotypes for gene: ADAM22 were changed from Developmental and epileptic encephalopathy 61 (MIM#617933) to Developmental and epileptic encephalopathy 61 (MIM#617933)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:34:00.700460+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12721","user_name":"Alison Yeung","item_type":"entity","text":"Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM#\t617933 to Developmental and epileptic encephalopathy 61 (MIM#617933)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:33:49.136289+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12720","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MDFIC as ready","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:33:49.123698+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12720","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mdfic has been classified as Green List (High Evidence).","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:33:41.057837+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12720","user_name":"Dean Phelan","item_type":"entity","text":"reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35289079; Phenotypes: early onset hypertension, proteinuria, progressive kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"TTC21B","entity_type":"gene"},{"created":"2022-04-07T11:33:34.514946+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12720","user_name":"Anna Ritchie","item_type":"entity","text":"changed review comment from: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.; to: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:33:28.256627+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12720","user_name":"Alison Yeung","item_type":"entity","text":"Publications for gene: ADAM22 were set to 27066583; 30237576","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:32:58.168685+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12719","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: ADAM22 as Green List (high evidence)","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:32:58.147968+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12719","user_name":"Alison Yeung","item_type":"entity","text":"Gene: adam22 has been classified as Green List (High Evidence).","entity_name":"ADAM22","entity_type":"gene"},{"created":"2022-04-07T11:32:54.786951+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1535","user_name":"Michelle Torres","item_type":"entity","text":"edited their review of gene: CACNA2D1: Changed phenotypes: developmental and epileptic encephalopathy disorder MONDO:0100062 CACNA2D1-related","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:32:19.057968+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4656","user_name":"Elena Savva","item_type":"entity","text":"gene: AHSG was added\ngene: AHSG was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: AHSG was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: AHSG were set to PMID: 28054173; 9395485; 31288248; 17389622\nPhenotypes for gene: AHSG were set to ?Alopecia-intellectual disability syndrome 1 MIM#203650; infantile cortical hyperostosis\nReview for gene: AHSG was set to RED\nAdded comment: PMID: 28054173 - 7 relatives within a large consanguinous fam w/ alopecia and ID, and a hom missense (p.Arg317His). Modelling predicts this variant to be a phosphorylation site, functional studies show a difference in protein size. Unclear biological significance.\r\nAlt change with stronger GS (p.(Arg317Cys)) is a common poly with 19 homozygotes in gnomAD.\r\n\r\nNo hom PTCs in gnomAD\r\n\r\nPMID: 9395485 - K/O mouse model shows no gross anatomical abnormalities, were fertile and \"healthy\". No mentioned of ID, alopecia\r\nPMID: 17389622 - K/O mouse model on the calcification resistant genetic background C57BL/6, shows uraemia and phosphate challenge. No mentioned of ID, alopecia\r\n\r\nPMID: 31288248 - 1 hom infant (p.K2*, within 5' NMD escape region) with infantile cortical hyperostosis, loss of enzyme in patient serum shown by ELISA. No mentioned of ID, alopecia \nSources: Literature","entity_name":"AHSG","entity_type":"gene"},{"created":"2022-04-07T11:32:01.384581+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12718","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MDFIC were changed from Central conducting lymphatic anomaly with lymphedema to Hydrops fetalis MONDO:0015193","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:30:46.465308+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4655","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: VPS16 as Green List (high evidence)","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:30:46.456302+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4655","user_name":"Ain Roesley","item_type":"entity","text":"Gene: vps16 has been classified as Green List (High Evidence).","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:30:39.307519+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12717","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MDFIC as Green List (high evidence)","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:30:39.295821+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12717","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mdfic has been classified as Green List (High Evidence).","entity_name":"MDFIC","entity_type":"gene"},{"created":"2022-04-07T11:30:26.299095+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4655","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: VPS16 as Green List (high evidence)","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:30:26.277832+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4655","user_name":"Ain Roesley","item_type":"entity","text":"Gene: vps16 has been classified as Green List (High Evidence).","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:30:22.892340+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1535","user_name":"Michelle Torres","item_type":"entity","text":"gene: CACNA2D1 was added\ngene: CACNA2D1 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CACNA2D1 were set to 35293990\nReview for gene: CACNA2D1 was set to GREEN\nAdded comment: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.\r\n\r\nPatient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts.\r\n\r\nPatient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Functional of the p.(Gly209Asp) showed it affects channel function due to impaired localisation. \nSources: Literature","entity_name":"CACNA2D1","entity_type":"gene"},{"created":"2022-04-07T11:30:13.507002+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4654","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: VPS16 as ready","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:30:13.497243+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4654","user_name":"Ain Roesley","item_type":"entity","text":"Gene: vps16 has been classified as Red List (Low Evidence).","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:29:55.365922+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12716","user_name":"Anna Ritchie","item_type":"entity","text":"reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: Craniosynostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"FUZ","entity_type":"gene"},{"created":"2022-04-07T11:29:46.215681+10:00","panel_name":"Iron metabolism disorders","panel_id":3469,"panel_version":"0.29","user_name":"Alison Yeung","item_type":"entity","text":"Marked gene: PIGA as ready","entity_name":"PIGA","entity_type":"gene"},{"created":"2022-04-07T11:29:46.204355+10:00","panel_name":"Iron metabolism disorders","panel_id":3469,"panel_version":"0.29","user_name":"Alison Yeung","item_type":"entity","text":"Gene: piga has been classified as Green List (High Evidence).","entity_name":"PIGA","entity_type":"gene"},{"created":"2022-04-07T11:29:42.843471+10:00","panel_name":"Iron metabolism disorders","panel_id":3469,"panel_version":"0.29","user_name":"Alison Yeung","item_type":"entity","text":"Classified gene: PIGA as Green List (high evidence)","entity_name":"PIGA","entity_type":"gene"},{"created":"2022-04-07T11:29:42.803920+10:00","panel_name":"Iron metabolism disorders","panel_id":3469,"panel_version":"0.29","user_name":"Alison Yeung","item_type":"entity","text":"Gene: piga has been classified as Green List (High Evidence).","entity_name":"PIGA","entity_type":"gene"},{"created":"2022-04-07T11:29:24.527011+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4654","user_name":"Ain Roesley","item_type":"entity","text":"gene: VPS16 was added\ngene: VPS16 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS16 were set to 33938619; 34013567; 34901436\nPhenotypes for gene: VPS16 were set to mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365\nReview for gene: VPS16 was set to GREEN\ngene: VPS16 was marked as current diagnostic\nAdded comment: for AR MPS - developmental delay reported\r\n3 unrelated families - 2x hom c.2272‐18C>A and 1x hom p.Trp180Cys\r\n\r\nRNA and functional studies done on the splice variant\r\n\r\nalso associated with AD dystonia\r\nPMID:34901436 suggests dystonia is transcript specific \nSources: Literature","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:29:23.495909+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12716","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TNNC1 were set to ","entity_name":"TNNC1","entity_type":"gene"},{"created":"2022-04-07T11:29:02.339939+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12715","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: TNNC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TNNC1","entity_type":"gene"},{"created":"2022-04-07T11:28:48.106164+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12714","user_name":"Krithika Murali","item_type":"entity","text":"gene: TNNI1 was added\ngene: TNNI1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: TNNI1 were set to 34934811\nPhenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures\nReview for gene: TNNI1 was set to AMBER\nAdded comment: No OMIM gene disease association reported\r\n\r\nPMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.\r\n\r\nThe proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.\r\n\r\nTrio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.\r\n\r\nThe affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts. \nSources: Literature","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:28:44.514566+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.12714","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TNNC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33947203, 31983221, 17977476, 19808376, 11385718, 8572189, 21262074, 22815480, 26779504; Phenotypes: Cardiomyopathy, dilated, 1Z, MIM# 611879, Cardiomyopathy, hypertrophic, 13 (MIM# 613243); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TNNC1","entity_type":"gene"},{"created":"2022-04-07T11:28:41.649416+10:00","panel_name":"Arthrogryposis","panel_id":47,"panel_version":"0.332","user_name":"Krithika Murali","item_type":"entity","text":"gene: TNNI1 was added\ngene: TNNI1 was added to Arthrogryposis. Sources: Literature\nMode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: TNNI1 were set to 34934811\nPhenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures\nReview for gene: TNNI1 was set to AMBER\nAdded comment: No OMIM gene disease association reported\r\n\r\nPMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.\r\n\r\nThe proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.\r\n\r\nTrio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.\r\n\r\nThe affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts. \nSources: Literature","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:28:33.068977+10:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.13","user_name":"Krithika Murali","item_type":"entity","text":"gene: TNNI1 was added\ngene: TNNI1 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: TNNI1 were set to 34934811\nPhenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures\nReview for gene: TNNI1 was set to AMBER\nAdded comment: No OMIM gene disease association reported\r\n\r\nPMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.\r\n\r\nThe proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.\r\n\r\nTrio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.\r\n\r\nThe affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts. \nSources: Literature","entity_name":"TNNI1","entity_type":"gene"},{"created":"2022-04-07T11:28:29.739494+10:00","panel_name":"Lysosomal Storage Disorder","panel_id":181,"panel_version":"1.6","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: VPS16 as Green List (high evidence)","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:28:29.721937+10:00","panel_name":"Lysosomal Storage Disorder","panel_id":181,"panel_version":"1.6","user_name":"Ain Roesley","item_type":"entity","text":"Gene: vps16 has been classified as Green List (High Evidence).","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:27:59.453685+10:00","panel_name":"Lysosomal Storage Disorder","panel_id":181,"panel_version":"1.6","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: VPS16 as Green List (high evidence)","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:27:59.442026+10:00","panel_name":"Lysosomal Storage Disorder","panel_id":181,"panel_version":"1.6","user_name":"Ain Roesley","item_type":"entity","text":"Gene: vps16 has been classified as Green List (High Evidence).","entity_name":"VPS16","entity_type":"gene"},{"created":"2022-04-07T11:27:31.602456+10:00","panel_name":"Lysosomal Storage Disorder","panel_id":181,"panel_version":"1.6","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: VPS16 as Green List (high evidence)","entity_name":"VPS16","entity_type":"gene"}]}