{"count":221304,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1692","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1690","results":[{"created":"2020-08-03T15:33:23.818657+10:00","panel_name":"Polymicrogyria and Schizencephaly","panel_id":18,"panel_version":"0.90","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MCF2 was added\ngene: MCF2 was added to Polymicrogyria and Schizencephaly. Sources: Literature\nMode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: MCF2 were set to 31846234\nPhenotypes for gene: MCF2 were set to Perisylvian polymicrogyria\nReview for gene: MCF2 was set to RED\nAdded comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model. \nSources: Literature","entity_name":"MCF2","entity_type":"gene"},{"created":"2020-08-03T15:33:07.300154+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2806","user_name":"Crystle Lee","item_type":"entity","text":"gene: SCAF4 was added\ngene: SCAF4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review\nMode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: SCAF4 were set to 32730804\nPhenotypes for gene: SCAF4 were set to Mild intellectual disability; seizures; behavioral abnormalities\nReview for gene: SCAF4 was set to GREEN\nAdded comment: > 5 variants reported in individuals with variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. \nSources: Expert Review","entity_name":"SCAF4","entity_type":"gene"},{"created":"2020-08-03T15:32:21.599919+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3644","user_name":"Crystle Lee","item_type":"entity","text":"gene: SCAF4 was added\ngene: SCAF4 was added to Mendeliome. Sources: Expert Review\nMode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: SCAF4 were set to 32730804\nPhenotypes for gene: SCAF4 were set to Mild intellectual disability; seizures; behavioral abnormalities\nReview for gene: SCAF4 was set to GREEN\nAdded comment: > 5 variants reported in individuals with variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. \nSources: Expert Review","entity_name":"SCAF4","entity_type":"gene"},{"created":"2020-08-03T13:22:19.354148+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"gene: DSC2 was added\ngene: DSC2 was added to Dilated Cardiomyopathy. Sources: Literature\nMode of inheritance for gene: DSC2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: DSC2 were set to 21859740\nPhenotypes for gene: DSC2 were set to Arrhythmogenic right ventricular dysplasia 11 with or without mild palmoplantar keratoderma and woolly hair MIM#610476\nReview for gene: DSC2 was set to AMBER\ngene: DSC2 was marked as current diagnostic\nAdded comment: ClinGen \"Definitive\" for ARVC. I can find no specific association with DCM, but this gene is green on the PanelApp GEL DCM panel for phenotypic overlap with DCM.\r\n\r\nOne VUS in DSC2 was identified in a patient who had undergone transplant for DCM (PMID: 21859740) (24 hets in gnomAD). \nSources: Literature","entity_name":"DSC2","entity_type":"gene"},{"created":"2020-08-03T12:55:29.358452+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"gene: DOLK was added\ngene: DOLK was added to Dilated Cardiomyopathy. Sources: Literature\nMode of inheritance for gene: DOLK was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: DOLK were set to 31741824; 28816422; 24144945; 22242004\nPhenotypes for gene: DOLK were set to Congenital disorder of glycosylation, type Im\tMIM#610768\nReview for gene: DOLK was set to AMBER\ngene: DOLK was marked as current diagnostic\nAdded comment: Not curated by ClinGen.\r\n\r\nThis is a CDG gene. Patients may present with DCM (among other phenotypes).\r\n\r\nPMID 22242004 describes 11 young (5-13) patients with \"predominantly nonsyndromic presentation of DCM\". \nSources: Literature","entity_name":"DOLK","entity_type":"gene"},{"created":"2020-08-03T11:47:30.696931+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"reviewed gene: CSRP3: Rating: RED; Mode of pathogenicity: None; Publications: 12507422, 14567970, 19412328; Phenotypes: ?Cardiomyopathy, dilated, 1M MIM#607482; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes","entity_name":"CSRP3","entity_type":"gene"},{"created":"2020-08-03T11:20:34.045215+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"changed review comment from: Not curated by ClinGen as of this review. Associated with DCM in OMIM but also myopathy and congenital cataracts (the association with the latter phenotypes is stronger).\r\n\r\n3 independent individuals/families with DCM reported that I could find. 1 additional report of RCM.\r\n\r\nPMID 16793013: 1 heterozygous missense variant in an individual with mild, late-onset DCM (200 patient cohort)\r\nPMID 16793013: 1 heterozygous missense variant in a 71-year-old individual with DCM (130 patient cohort). Functional studies showed impared binding to TTN.\r\nPMID 23590293: 1 heterozygous stop-loss variant identified in a family with congenital cataracts and DCM, although not all members of the family with the variant had DCM.\r\nPMID 29253866: variant identified in an individual with restrictive cardiomyopathy (cohort study)\r\n\r\nAmber in PanelApp GEL\r\n\r\nI don't think there's sufficient evidence for an association with DCM so I am marking this red.; to: Not curated by ClinGen as of this review. Associated with DCM in OMIM but also myopathy and congenital cataracts (the association with the latter phenotypes is stronger).\r\n\r\n3 independent individuals/families with DCM reported that I could find. 1 additional report of RCM.\r\n\r\nPMID 16793013: 1 heterozygous missense variant in an individual with mild, late-onset DCM (200 patient cohort) (253 hets in gnomAD)\r\nPMID 16483541: 1 heterozygous missense variant in a 71-year-old individual with DCM (130 patient cohort). Functional studies showed impared binding to TTN  (18 hets in gnomad). \r\nPMID 23590293: 1 heterozygous stop-loss variant identified in a family with congenital cataracts and DCM, although not all members of the family with the variant had DCM.\r\nPMID 29253866: variant identified in an individual with restrictive cardiomyopathy (cohort study)\r\n\r\nAmber in PanelApp GEL\r\n\r\nI don't think there's sufficient evidence for an association with DCM so I am marking this red.","entity_name":"CRYAB","entity_type":"gene"},{"created":"2020-08-03T11:12:31.362621+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"reviewed gene: CRYAB: Rating: RED; Mode of pathogenicity: None; Publications: 16793013, 16483541, 23590293, 29253866; Phenotypes: Cardiomyopathy, dilated, 1II MIM#615184; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes","entity_name":"CRYAB","entity_type":"gene"},{"created":"2020-08-03T10:31:49.612604+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"changed review comment from: Associated with ARVC. \"Limited evidence\" for ARVC by ClinGen. \r\n\r\nCardiac cell-specific knockout mice develop DCM (PMID: 15662031) but I can find no evidence of disease in humans.\r\n\r\nGreen in PanelApp GEL but did not achieve consensus green rating. \nSources: Literature; to: Associated with ARVC. \"Limited evidence\" for ARVC by ClinGen. \r\n\r\nCardiac cell-specific knockout mice develop DCM (PMID: 15662031) but I can find no evidence of DCM in humans.\r\n\r\nGreen in PanelApp GEL but did not achieve consensus green rating. \r\nSources: Literature","entity_name":"CDH2","entity_type":"gene"},{"created":"2020-08-03T10:31:31.780873+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"gene: CDH2 was added\ngene: CDH2 was added to Dilated Cardiomyopathy. Sources: Literature\nMode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: CDH2 were set to 28280076; 15662031\nPhenotypes for gene: CDH2 were set to Arrhythmogenic right ventricular dysplasia, familial, 14 MIM#618920\nReview for gene: CDH2 was set to RED\ngene: CDH2 was marked as current diagnostic\nAdded comment: Associated with ARVC. \"Limited evidence\" for ARVC by ClinGen. \r\n\r\nCardiac cell-specific knockout mice develop DCM (PMID: 15662031) but I can find no evidence of disease in humans.\r\n\r\nGreen in PanelApp GEL but did not achieve consensus green rating. \nSources: Literature","entity_name":"CDH2","entity_type":"gene"},{"created":"2020-08-03T10:12:10.450606+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"0.43","user_name":"Paul De Fazio","item_type":"entity","text":"gene: ACTN2 was added\ngene: ACTN2 was added to Dilated Cardiomyopathy. Sources: Literature\nMode of inheritance for gene: ACTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: ACTN2 were set to 20474083; 25224718; 22253474; 14567970:\nPhenotypes for gene: ACTN2 were set to Intrinsic cardiomyopathy\nReview for gene: ACTN2 was set to AMBER\ngene: ACTN2 was marked as current diagnostic\nAdded comment: Moderate evidence for \"intrinsic cardiomyopathy\" according to ClinGen. Associated with both HCM and DCM (same MIM# for both). \r\n\r\nAccording to ClinGen; 12 unique heterozygous variants have been identified in the context of diverse cardiac phenotypes (HCM, DCM, LVNC, ventricular fibrillation).\r\n\r\nIn DCM:\r\nPMID 20474083: 3 \"variants of likely clinical significance\" and 1 VUS, cohort study\r\nPMID 14567970: missense variant in a child who died of DCM\r\nPMID 25224718: 2 families with the same missense variant (same haplotype)\r\n\r\nRescues a DCM phenotype in Zebrafish (PMID: 22253474).\r\n\r\nGreen on PanelApp GEL but did not achieve consensus Green rating. Amber on PanelApp Aus HCM panel. \nSources: Literature","entity_name":"ACTN2","entity_type":"gene"},{"created":"2020-08-03T09:04:18.747833+10:00","panel_name":"Hereditary Neuropathy - complex","panel_id":3070,"panel_version":"0.77","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NARS as ready","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:04:18.739574+10:00","panel_name":"Hereditary Neuropathy - complex","panel_id":3070,"panel_version":"0.77","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:04:13.762981+10:00","panel_name":"Hereditary Neuropathy - complex","panel_id":3070,"panel_version":"0.77","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NARS as Green List (high evidence)","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:04:13.753030+10:00","panel_name":"Hereditary Neuropathy - complex","panel_id":3070,"panel_version":"0.77","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:04:04.287597+10:00","panel_name":"Hereditary Neuropathy - complex","panel_id":3070,"panel_version":"0.76","user_name":"Zornitza Stark","item_type":"entity","text":"gene: NARS was added\ngene: NARS was added to Hereditary Neuropathy - complex. Sources: Literature\nnew gene name tags were added to gene: NARS.\nMode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: NARS were set to 32738225\nPhenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy\nReview for gene: NARS was set to GREEN\nAdded comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). \nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:02:32.511221+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3644","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NARS as ready","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:02:32.500141+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3644","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:02:24.669281+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3644","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NARS as Green List (high evidence)","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:02:24.658939+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3644","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:02:08.117881+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3643","user_name":"Zornitza Stark","item_type":"entity","text":"gene: NARS was added\ngene: NARS was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: NARS were set to 32738225\nPhenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy\nReview for gene: NARS was set to GREEN\nAdded comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). \nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:00:17.970595+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.767","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NARS as ready","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:00:17.957685+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.767","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:00:14.779356+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.767","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NARS as Green List (high evidence)","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T09:00:14.771150+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.767","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:59:52.636006+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.766","user_name":"Zornitza Stark","item_type":"entity","text":"Tag new gene name tag was added to gene: NARS.","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:59:37.333817+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2806","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NARS as ready","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:59:37.319924+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2806","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:59:30.141289+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2806","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NARS as Green List (high evidence)","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:59:30.131075+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2806","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nars has been classified as Green List (High Evidence).","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T08:58:45.091038+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Tag new gene name tag was added to gene: NARS.","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T00:10:27.930465+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"changed review comment from: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. \r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. \r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \nSources: Literature; to: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. \r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. \r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \r\nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T00:09:42.475604+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.766","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"changed review comment from: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.\r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.\r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \nSources: Literature; to: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.\r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.\r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \r\nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T00:06:46.690310+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.766","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: NARS was added\ngene: NARS was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: NARS were set to 32738225\nPhenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy\nPenetrance for gene: NARS were set to Complete\nReview for gene: NARS was set to GREEN\nAdded comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.\r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.\r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-03T00:03:51.781144+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: NARS was added\ngene: NARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: NARS were set to 32738225\nPhenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy\nPenetrance for gene: NARS were set to Complete\nReview for gene: NARS was set to GREEN\nAdded comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]\r\n\r\nManole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. \r\n\r\nSimilar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. \r\n\r\nNARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.\r\n\r\nSome variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].\r\n\r\nThe authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).\r\n\r\nAs also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy. \nSources: Literature","entity_name":"NARS","entity_type":"gene"},{"created":"2020-08-02T21:08:25.216968+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3642","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ZNF407 as ready","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:08:25.206848+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3642","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: znf407 has been classified as Amber List (Moderate Evidence).","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:08:18.577990+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3642","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ZNF407 were changed from  to Global developmental delay; Intellectual disability","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:07:54.441917+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3641","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ZNF407 were set to ","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:07:34.393273+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3640","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: ZNF407 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:07:13.574251+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3639","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ZNF407 as Amber List (moderate evidence)","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:07:13.565854+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3639","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: znf407 has been classified as Amber List (Moderate Evidence).","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:06:55.935491+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3638","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ZNF407: Rating: AMBER; Mode of pathogenicity: None; Publications: 24907849, 32737394, 23195952; Phenotypes: Global developmental delay, Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:05:16.714806+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ZNF407 as ready","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:05:16.711262+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: Evidence both for mono allelic and bi-allelic disease, though neither sufficient for Green rating at present.","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:05:16.683815+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: znf407 has been classified as Amber List (Moderate Evidence).","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:04:39.853546+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ZNF407 as Amber List (moderate evidence)","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:04:39.845119+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2805","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: znf407 has been classified as Amber List (Moderate Evidence).","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T21:02:23.670080+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2804","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: ZNF407 was added\ngene: ZNF407 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: ZNF407 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: ZNF407 were set to 24907849; 32737394; 23195952\nPhenotypes for gene: ZNF407 were set to Global developmental delay; Intellectual disability\nPenetrance for gene: ZNF407 were set to unknown\nReview for gene: ZNF407 was set to AMBER\nAdded comment: You may consider inclusion of this gene probably with amber rating (or green if the evidence for biallelic variants is considered sufficient).\r\n\r\nBiallelic variants:\r\n\r\n- Kambouris et al. (2014 - PMID: 24907849) described 2 brothers with severe DD and ID, born to first cousin parents. Homozygosity mapping, following other non-diagnostic investigations (incl. aCGH), revealed 4 major homozygosity intervals. Exome sequencing in one identified 5 variants within these intervals, ZNF407 (c.5054C>G, p.Ser1685Trp) being the best candidate, supported also by segregation studies. The authors commented that zinc finger proteins act as transcriptional regulators, with mutations in genes encoding for other zinc finger proteins interfering with normal brain development.\r\n\r\n- Zahra et al. (2020 - PMID: 32737394) report on 7 affected individuals (from 3 families) homozygous or compound heterozygous for ZNF407 variants. Features included hypotonia, DD and ID (in all) and variable occurrence of short stature (6/6), microcephaly (in at least 5), behavioural, visual problems and deafness.  Linkage analysis in the first family revealed a 4.4 Mb shared homozygosity region and exome (30x) revealed a 3-bp duplication, confirmed by Sanger sequencing and segregating with the disease (NM_001146189:c.2814_2816dup, p.Val939dup). Affected subjects from the 2 other families were each found to be homozygous (c.2405G>T) or compound heterozygous (c.2884C>G, c.3642G>C) for other variants. Segregation was compatible in all families. Other studies were not performed. The authors comment than only the 3-bp duplication fullfilled ACMG criteria for classification as LP, the other variants being all formally classified as VUS (also due to in silico predictions predicting a LB effect). In addition, while several features such as DD/ID and short stature appeared to be frequent among all patients reported, Zahra et all comment that there was partial clinical overlap with the sibs described by Kambouris et al (additional variants?).\r\n\r\n\r\nMonoallelic disruption of ZNF407:\r\n\r\n- Ren et al (2013 - PMID: 23195952) described an 8 y.o. boy with ID and ASD. The boy was found to harbor a de novo translocation between chromosomes 3 and 18 [46,XY,t(3;18)(p13;q22.3)]. Array CGH did not reveal any P/LP CNV. Delineation of the breakpoints (FISH, long-range PCR) revealed that the chr18 breakpoint disrupted intron 3 of ZNF407 (isoform 1) with the other breakpoint within a gene-free region of exon 3. There was a loss of 4-8 nt in chr18 and 2-6 in chr3. Sequencing of ZNF407 did not reveal additional variants. RNA isolation in blood followed by RT-PCR studied expression of all 3 ZNF407 isoforms (the intronic region being shared by isoforms 1 and 2). Expression of isoform 1 was shown to be significantly reduced compared to controls. Isoform 2 was undetectable (in blood) while isoform 3 expression was similar to controls. Sequencing of 105 additional patients with similar clinical presentation (ID & ASD) revealed 2 further individuals with de novo missense variants.\r\n\r\n- Based on the discussion by Kambouris et al (PMID: 24907849 - cited literature not here reviewed) ZNF407 may be deleted in patients with congenital aural atresia due to deletion of a critical region of 18q22.3 (though TSHZ1 is responsible for this phenotype) or 18q- although such deletions span several other genes (cited PMID: 16639285). In one case the breakpoint was shown to be disrupting ZNF407 (cited PMID: 24092497).  \r\n\r\n- The denovo db and Decipher (research variant tab) list few individuals with de novo ZNF407 SNVs although these do not seem to allow conclusions.\r\n\r\nhttps://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=ZNF407\r\nhttps://decipher.sanger.ac.uk/search/ddd-research-variants/results?q=znf407 \nSources: Literature","entity_name":"ZNF407","entity_type":"gene"},{"created":"2020-08-02T20:35:43.978297+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.46","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: OCRL as ready","entity_name":"OCRL","entity_type":"gene"},{"created":"2020-08-02T20:35:43.967983+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.46","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ocrl has been classified as Green List (High Evidence).","entity_name":"OCRL","entity_type":"gene"},{"created":"2020-08-02T20:33:35.197020+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.46","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: OCRL as Green List (high evidence)","entity_name":"OCRL","entity_type":"gene"},{"created":"2020-08-02T20:33:35.186665+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.46","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ocrl has been classified as Green List (High Evidence).","entity_name":"OCRL","entity_type":"gene"},{"created":"2020-08-02T20:33:13.748285+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.45","user_name":"Zornitza Stark","item_type":"entity","text":"gene: OCRL was added\ngene: OCRL was added to Glaucoma congenital. Sources: Expert list\nMode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPhenotypes for gene: OCRL were set to Lowe syndrome, MIM#\t309000\nReview for gene: OCRL was set to GREEN\nAdded comment: Glaucoma present in ~50%, GeneReviews. \nSources: Expert list","entity_name":"OCRL","entity_type":"gene"},{"created":"2020-08-02T20:27:09.748678+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.44","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: IFIH1 as ready","entity_name":"IFIH1","entity_type":"gene"},{"created":"2020-08-02T20:27:09.739749+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.44","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ifih1 has been classified as Green List (High Evidence).","entity_name":"IFIH1","entity_type":"gene"},{"created":"2020-08-02T20:26:58.813685+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.44","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: IFIH1 as Green List (high evidence)","entity_name":"IFIH1","entity_type":"gene"},{"created":"2020-08-02T20:26:58.805468+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.44","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ifih1 has been classified as Green List (High Evidence).","entity_name":"IFIH1","entity_type":"gene"},{"created":"2020-08-02T20:26:34.745486+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.43","user_name":"Zornitza Stark","item_type":"entity","text":"gene: IFIH1 was added\ngene: IFIH1 was added to Glaucoma congenital. Sources: Expert list\nMode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: IFIH1 were set to Singleton-Merten syndrome 1, MIM#\t182250\nReview for gene: IFIH1 was set to GREEN\nAdded comment: Glaucoma is a feature of this condition. \nSources: Expert list","entity_name":"IFIH1","entity_type":"gene"},{"created":"2020-08-02T20:24:53.306206+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3638","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: DDX58 as ready","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:24:53.298180+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3638","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ddx58 has been classified as Green List (High Evidence).","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:24:32.588650+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3638","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: DDX58 were changed from  to Singleton-Merten syndrome 2, MIM# 616298","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:24:12.470796+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3637","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DDX58 were set to ","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:23:56.992127+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3636","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: DDX58 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:23:38.821191+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3635","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.; to: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies. At least 3 families reported.","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:21:05.412174+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3635","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620203; Phenotypes: Singleton-Merten syndrome 2, MIM# 616298; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:19:08.724967+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: DDX58 as ready","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:19:08.713573+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ddx58 has been classified as Amber List (Moderate Evidence).","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:18:49.489115+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: DDX58 as Amber List (moderate evidence)","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:18:49.478277+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ddx58 has been classified as Amber List (Moderate Evidence).","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T20:18:21.831135+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.41","user_name":"Zornitza Stark","item_type":"entity","text":"gene: DDX58 was added\ngene: DDX58 was added to Glaucoma congenital. Sources: Expert list\nMode of inheritance for gene: DDX58 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: DDX58 were set to 25620203\nPhenotypes for gene: DDX58 were set to Singleton-Merten syndrome 2, MIM#\t616298\nReview for gene: DDX58 was set to AMBER\nAdded comment: At least two families reported where glaucoma was a feature of the presenting phenotype. \nSources: Expert list","entity_name":"DDX58","entity_type":"gene"},{"created":"2020-08-02T19:18:23.823780+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.40","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TEK were changed from  to Glaucoma 3, primary congenital, E, MIM# 617272","entity_name":"TEK","entity_type":"gene"},{"created":"2020-08-02T19:18:03.519301+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.39","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TEK were set to ","entity_name":"TEK","entity_type":"gene"},{"created":"2020-08-02T19:17:26.732514+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.38","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: TEK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TEK","entity_type":"gene"},{"created":"2020-08-02T19:17:04.364733+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.37","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TEK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27270174; Phenotypes: Glaucoma 3, primary congenital, E, MIM# 617272; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TEK","entity_type":"gene"},{"created":"2020-08-02T19:13:12.949118+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.37","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SH3PXD2B as ready","entity_name":"SH3PXD2B","entity_type":"gene"},{"created":"2020-08-02T19:13:12.940479+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.37","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sh3pxd2b has been classified as Green List (High Evidence).","entity_name":"SH3PXD2B","entity_type":"gene"},{"created":"2020-08-02T19:13:10.308406+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.37","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SH3PXD2B were changed from  to Frank-ter Haar syndrome, MIM# 249420","entity_name":"SH3PXD2B","entity_type":"gene"},{"created":"2020-08-02T19:12:43.906085+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.36","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SH3PXD2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SH3PXD2B","entity_type":"gene"},{"created":"2020-08-02T19:12:17.607075+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.35","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SH3PXD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Frank-ter Haar syndrome, MIM# 249420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SH3PXD2B","entity_type":"gene"},{"created":"2020-08-02T19:10:01.085629+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.35","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SBF2 as ready","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:10:01.076136+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.35","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sbf2 has been classified as Green List (High Evidence).","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:09:58.222260+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.35","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SBF2 were changed from  to Charcot-Marie-Tooth disease, type 4B2, MIM# 604563","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:09:33.333104+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.34","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SBF2 were set to ","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:09:13.007804+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.33","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SBF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:08:50.561137+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.32","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SBF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12687498, 15304601; Phenotypes: Charcot-Marie-Tooth disease, type 4B2, MIM# 604563; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SBF2","entity_type":"gene"},{"created":"2020-08-02T19:05:36.709456+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.32","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: POMGNT1 as ready","entity_name":"POMGNT1","entity_type":"gene"},{"created":"2020-08-02T19:05:36.690247+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.32","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pomgnt1 has been classified as Green List (High Evidence).","entity_name":"POMGNT1","entity_type":"gene"},{"created":"2020-08-02T19:05:32.256598+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.32","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: POMGNT1 as Green List (high evidence)","entity_name":"POMGNT1","entity_type":"gene"},{"created":"2020-08-02T19:05:32.248639+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.32","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pomgnt1 has been classified as Green List (High Evidence).","entity_name":"POMGNT1","entity_type":"gene"},{"created":"2020-08-02T19:05:10.275067+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.31","user_name":"Zornitza Stark","item_type":"entity","text":"gene: POMGNT1 was added\ngene: POMGNT1 was added to Glaucoma congenital. Sources: Expert list\nMode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, MIM#\t253280\nReview for gene: POMGNT1 was set to GREEN\nAdded comment: Glaucoma is part of the ocular phenotype. \nSources: Expert list","entity_name":"POMGNT1","entity_type":"gene"},{"created":"2020-08-02T19:04:04.983742+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.30","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: POMT1 as ready","entity_name":"POMT1","entity_type":"gene"},{"created":"2020-08-02T19:04:04.966412+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.30","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pomt1 has been classified as Green List (High Evidence).","entity_name":"POMT1","entity_type":"gene"},{"created":"2020-08-02T19:03:04.495286+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.30","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: POMT1 were changed from  to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, MIM# 236670","entity_name":"POMT1","entity_type":"gene"},{"created":"2020-08-02T19:02:33.426058+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.29","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: POMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"POMT1","entity_type":"gene"},{"created":"2020-08-02T19:02:06.906086+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, MIM# 236670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"POMT1","entity_type":"gene"},{"created":"2020-08-02T19:01:04.204242+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PIK3R1 as ready","entity_name":"PIK3R1","entity_type":"gene"},{"created":"2020-08-02T19:01:04.193644+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pik3r1 has been classified as Green List (High Evidence).","entity_name":"PIK3R1","entity_type":"gene"},{"created":"2020-08-02T18:58:56.064762+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PIK3R1 were changed from  to SHORT syndrome, MIM# 269880","entity_name":"PIK3R1","entity_type":"gene"},{"created":"2020-08-02T18:58:32.312515+10:00","panel_name":"Glaucoma congenital","panel_id":105,"panel_version":"0.27","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: PIK3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"PIK3R1","entity_type":"gene"}]}