{"count":221763,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=478","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=476","results":[{"created":"2024-04-04T07:10:45.689896+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5737","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:10:12.090545+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5736","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: USP27X were set to 25644381","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:09:39.265713+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5735","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP27X as Green List (high evidence)","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:09:39.253880+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5735","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp27x has been classified as Green List (High Evidence).","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:09:01.331725+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5734","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:08:29.852772+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1643","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:08:10.505357+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1642","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: USP27X were set to 25644381","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:07:49.589404+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1641","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP27X as Green List (high evidence)","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:07:49.580855+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1641","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp27x has been classified as Green List (High Evidence).","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-04T07:07:30.757765+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1640","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984","entity_name":"USP27X","entity_type":"gene"},{"created":"2024-04-03T19:23:34.511850+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1640","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: ZNF143 as Amber List (moderate evidence)","entity_name":"ZNF143","entity_type":"gene"},{"created":"2024-04-03T19:23:34.503269+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1640","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: znf143 has been classified as Amber List (Moderate Evidence).","entity_name":"ZNF143","entity_type":"gene"},{"created":"2024-04-03T19:23:16.477717+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1639","user_name":"Bryony Thompson","item_type":"entity","text":"reviewed gene: ZNF143: Rating: AMBER; Mode of pathogenicity: None; Publications: 27349184, 33845046, 9009278, 22268977, 27349184, 27349184; Phenotypes: methylmalonic aciduria and homocystinuria MONDO:0016826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ZNF143","entity_type":"gene"},{"created":"2024-04-03T19:20:38.211972+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1639","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: TCN1 as ready","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T19:20:38.202383+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1639","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: tcn1 has been classified as Amber List (Moderate Evidence).","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T19:20:25.258184+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1639","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TCN1 as Amber List (moderate evidence)","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T19:20:25.244806+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1639","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: tcn1 has been classified as Amber List (Moderate Evidence).","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T19:20:05.829469+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1638","user_name":"Bryony Thompson","item_type":"entity","text":"gene: TCN1 was added\ngene: TCN1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TCN1 were set to 29764838; 19686235\nPhenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659\nReview for gene: TCN1 was set to AMBER\nAdded comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease \nSources: Literature","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T17:41:32.428001+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1637","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: FEM1B as Green List (high evidence)","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:41:32.420375+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1637","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: fem1b has been classified as Green List (High Evidence).","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:41:11.184818+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1636","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: FEM1B were set to PMID: 31036916","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:40:45.783124+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1635","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:40:40.756899+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5734","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:40:04.728241+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5733","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: FEM1B were set to 31036916","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:39:49.460834+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:39:13.081750+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5732","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: FEM1B as Green List (high evidence)","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:39:13.069468+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5732","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: fem1b has been classified as Green List (High Evidence).","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:38:34.970668+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5731","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related","entity_name":"FEM1B","entity_type":"gene"},{"created":"2024-04-03T17:36:38.255024+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5731","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: USP14 as ready","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:36:38.246277+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5731","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Amber List (Moderate Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:36:27.562384+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5731","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP14 as Amber List (moderate evidence)","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:36:27.546654+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5731","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Amber List (Moderate Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:35:29.314292+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5730","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP14 as Amber List (moderate evidence)","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:35:29.283982+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5730","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Amber List (Moderate Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:34:49.449890+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5729","user_name":"Zornitza Stark","item_type":"entity","text":"gene: USP14 was added\ngene: USP14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: USP14 were set to 38469793; 35066879\nPhenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related\nReview for gene: USP14 was set to AMBER\nAdded comment: AMBER rating as two of the families had affected fetuses, one had a severely affected newborn, and fourth had a progressive course: none fit well with ID, though there's likely to be a continuum.\r\n\r\nPMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.\r\n\r\nPMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations. \nSources: Literature","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T17:29:29.993887+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: DISP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 38529886; Phenotypes: Holoprosencephaly (MONDO:0016296); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"DISP1","entity_type":"gene"},{"created":"2024-04-03T15:49:42.469460+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"gene: TRPV5 was added\ngene: TRPV5 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRPV5 were set to PMID: 38528055\nPhenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)\nReview for gene: TRPV5 was set to RED\nAdded comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.\r\n\r\nPMID: 38528055\r\n3 individuals from the same family affected with hypercalciuria. \r\nBiallelic Met598Val variant was identified in the proband and his two affect sibs\r\n\r\nFunctional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used. \nSources: Other","entity_name":"TRPV5","entity_type":"gene"},{"created":"2024-04-03T15:01:55.262779+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5728","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: DOCK4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38526744; Phenotypes: DOCK4-related neurodevelopmental disorder (MONDO:0060490); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown","entity_name":"DOCK4","entity_type":"gene"},{"created":"2024-04-03T13:54:00.830559+11:00","panel_name":"Metabolic Disorders Superpanel","panel_id":3465,"panel_version":"8.125","user_name":"Bryony Thompson","item_type":"panel","text":"Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia","entity_name":null,"entity_type":null},{"created":"2024-04-03T12:37:28.620948+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.44","user_name":"Bryony Thompson","item_type":"entity","text":"Tag pharmacogenomic tag was added to gene: DPYD.","entity_name":"DPYD","entity_type":"gene"},{"created":"2024-04-03T11:29:45.753208+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.521","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: USP14 were set to PMID: 35066879","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:27:12.549192+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP14 as Green List (high evidence)","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:27:12.539083+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Green List (High Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:22:29.941446+11:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.519","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:21:25.185129+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.222","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: USP14 were set to PMID: 35066879","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:20:09.492229+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.221","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP14 as Green List (high evidence)","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:20:09.483474+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.221","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Green List (High Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:19:56.950159+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.220","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:19:13.094635+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: USP14 as ready","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:19:13.086965+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Green List (High Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:19:01.900436+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP14 as Green List (high evidence)","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:19:01.889503+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1634","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp14 has been classified as Green List (High Evidence).","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T11:18:31.360657+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1633","user_name":"Zornitza Stark","item_type":"entity","text":"gene: USP14 was added\ngene: USP14 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: USP14 were set to 38469793; 35066879\nPhenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related\nReview for gene: USP14 was set to GREEN\nAdded comment: PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.\r\n\r\nPMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations. \nSources: Literature","entity_name":"USP14","entity_type":"gene"},{"created":"2024-04-03T10:17:22.443540+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"1.0","user_name":"Bryony Thompson","item_type":"panel","text":"promoted panel to version 1.0","entity_name":null,"entity_type":null},{"created":"2024-04-03T10:00:41.613997+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.44","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:THAP11 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:59:32.627054+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.43","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:ZNF143 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:57:17.710697+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.42","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:TCN2 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:55:22.245995+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.41","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:MTR from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:53:58.673367+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.40","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:MMADHC from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:53:41.262378+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.36","user_name":"Bryony Thompson","item_type":"entity","text":"Tag treatable tag was added to gene: MMADHC.","entity_name":"MMADHC","entity_type":"gene"},{"created":"2024-04-03T09:53:27.802035+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.39","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:MMACHC from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:53:12.779242+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.36","user_name":"Bryony Thompson","item_type":"entity","text":"Tag treatable tag was added to gene: MMACHC.","entity_name":"MMACHC","entity_type":"gene"},{"created":"2024-04-03T09:52:25.177924+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.38","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:LMBRD1 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:52:07.162044+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.36","user_name":"Bryony Thompson","item_type":"entity","text":"Tag treatable tag was added to gene: LMBRD1.","entity_name":"LMBRD1","entity_type":"gene"},{"created":"2024-04-03T09:51:30.664900+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.37","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:HCFC1 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:50:33.998615+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.36","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:GIF from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:43:31.924173+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.35","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:CUBN from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:40:51.123897+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.36","user_name":"Bryony Thompson","item_type":"entity","text":"Tag treatable tag was added to gene: CUBN.","entity_name":"CUBN","entity_type":"gene"},{"created":"2024-04-03T09:40:32.789595+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.34","user_name":"Bryony Thompson","item_type":"entity","text":"Phenotypes for gene: CBS were changed from Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism; metabolic disorder of sulfur metabolism","entity_name":"CBS","entity_type":"gene"},{"created":"2024-04-03T09:38:06.846419+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.33","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:AMN from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:36:49.951104+11:00","panel_name":"Miscellaneous Metabolic Disorders","panel_id":3468,"panel_version":"1.32","user_name":"Bryony Thompson","item_type":"panel","text":"removed gene:ABCD4 from the panel","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:36:14.434569+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.36","user_name":"Bryony Thompson","item_type":"entity","text":"Phenotypes for gene: ABCD4 were changed from Methylmalonic aciduria and homocystinuria, cblJ type\tMIM#614857 to Methylmalonic aciduria and homocystinuria, cblJ type\tMIM#614857; disorder of vitamin B12 metabolism","entity_name":"ABCD4","entity_type":"gene"},{"created":"2024-04-03T09:28:21.875858+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.35","user_name":"Bryony Thompson","item_type":"panel","text":"Panel status changed from internal to public","entity_name":null,"entity_type":null},{"created":"2024-04-03T09:27:36.569958+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: TCN1 as ready","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:27:36.560708+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: tcn1 has been classified as Amber List (Moderate Evidence).","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:27:24.360926+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"changed review comment from: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels \nSources: Literature; to: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease\r\nSources: Literature","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:23:01.671905+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"edited their review of gene: TCN1: Changed publications: 29764838, 19686235","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:19:26.563067+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TCN1 as Amber List (moderate evidence)","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:19:26.555124+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.34","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: tcn1 has been classified as Amber List (Moderate Evidence).","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T09:19:10.124525+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.33","user_name":"Bryony Thompson","item_type":"entity","text":"gene: TCN1 was added\ngene: TCN1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature\nMode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TCN1 were set to 19686235\nPhenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659\nReview for gene: TCN1 was set to AMBER\nAdded comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels \nSources: Literature","entity_name":"TCN1","entity_type":"gene"},{"created":"2024-04-03T08:45:42.814477+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.5728","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118","entity_name":"ZFX","entity_type":"gene"},{"created":"2024-04-03T08:44:57.708622+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1632","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118","entity_name":"ZFX","entity_type":"gene"},{"created":"2024-04-03T08:44:01.071776+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.1631","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ZFX: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118","entity_name":"ZFX","entity_type":"gene"},{"created":"2024-04-03T08:25:51.006517+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.32","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: MTRR as ready","entity_name":"MTRR","entity_type":"gene"},{"created":"2024-04-03T08:25:50.986293+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.32","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mtrr has been classified as Green List (High Evidence).","entity_name":"MTRR","entity_type":"gene"},{"created":"2024-04-03T08:25:48.805602+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.32","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: MTRR as Green List (high evidence)","entity_name":"MTRR","entity_type":"gene"},{"created":"2024-04-03T08:25:48.795026+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.32","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mtrr has been classified as Green List (High Evidence).","entity_name":"MTRR","entity_type":"gene"},{"created":"2024-04-03T08:25:38.711309+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.31","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: MTR as ready","entity_name":"MTR","entity_type":"gene"},{"created":"2024-04-03T08:25:38.697110+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.31","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mtr has been classified as Green List (High Evidence).","entity_name":"MTR","entity_type":"gene"},{"created":"2024-04-03T08:25:35.857191+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.31","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: MTR as Green List (high evidence)","entity_name":"MTR","entity_type":"gene"},{"created":"2024-04-03T08:25:35.848051+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.31","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mtr has been classified as Green List (High Evidence).","entity_name":"MTR","entity_type":"gene"},{"created":"2024-04-03T08:25:28.518041+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: MMADHC as ready","entity_name":"MMADHC","entity_type":"gene"},{"created":"2024-04-03T08:25:28.506360+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mmadhc has been classified as Green List (High Evidence).","entity_name":"MMADHC","entity_type":"gene"},{"created":"2024-04-03T08:25:17.602963+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: MMADHC as Green List (high evidence)","entity_name":"MMADHC","entity_type":"gene"},{"created":"2024-04-03T08:25:17.577236+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mmadhc has been classified as Green List (High Evidence).","entity_name":"MMADHC","entity_type":"gene"},{"created":"2024-04-03T08:24:57.685954+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.29","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: MMACHC as ready","entity_name":"MMACHC","entity_type":"gene"},{"created":"2024-04-03T08:24:57.677295+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.29","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mmachc has been classified as Green List (High Evidence).","entity_name":"MMACHC","entity_type":"gene"},{"created":"2024-04-03T08:24:49.636421+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.29","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: MMACHC as Green List (high evidence)","entity_name":"MMACHC","entity_type":"gene"},{"created":"2024-04-03T08:24:49.628827+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.29","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: mmachc has been classified as Green List (High Evidence).","entity_name":"MMACHC","entity_type":"gene"},{"created":"2024-04-03T08:24:36.553030+11:00","panel_name":"Inherited vitamin B12 or cobalamin deficiency","panel_id":4257,"panel_version":"0.28","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: LMBRD1 as ready","entity_name":"LMBRD1","entity_type":"gene"}]}