{"count":220459,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1527","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1525","results":[{"created":"2020-10-25T12:49:39.376865+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.890","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from  to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T12:49:10.450342+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.889","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:51:42.029223+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.888","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:51:16.767769+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.887","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SCO1 as Amber List (moderate evidence)","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:51:16.757911+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.887","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Amber List (Moderate Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:50:48.387898+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.886","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:55.592795+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.29","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SCO1 as Amber List (moderate evidence)","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:55.584445+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.29","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Amber List (Moderate Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:46.672899+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCO1 as ready","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:46.662147+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Green List (High Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:44.384911+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.28","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:31.264795+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.27","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:44:18.947642+11:00","panel_name":"Cardiomyopathy_Paediatric","panel_id":3270,"panel_version":"0.26","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:43:07.825523+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3106","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCO1 as ready","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:43:07.812575+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3106","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Red List (Low Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:42:14.647724+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3106","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from  to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:41:30.365208+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3105","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:41:04.204711+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3104","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:40:37.702995+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3103","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SCO1 as Red List (low evidence)","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:40:37.695402+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3103","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Red List (Low Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:40:06.356119+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T10:06:20.494825+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5102","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACB was added\ngene: PRKACB was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACB were set to 33058759\nPhenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACB were set to unknown\nMode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACB was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T10:06:16.016292+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5102","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACA was added\ngene: PRKACA was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACA were set to 33058759; 31130284\nPhenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACA were set to unknown\nMode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACA was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACA","entity_type":"gene"},{"created":"2020-10-25T10:03:29.687942+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.180","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"commented on gene: PRKACA: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]","entity_name":"PRKACA","entity_type":"gene"},{"created":"2020-10-25T10:02:17.498528+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.180","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"commented on gene: PRKACB: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T09:59:28.975106+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.78","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACA was added\ngene: PRKACA was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACA were set to 33058759; 31130284\nPhenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACA were set to unknown\nMode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACA was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACA","entity_type":"gene"},{"created":"2020-10-25T09:57:32.575148+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.78","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACB was added\ngene: PRKACB was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACB were set to 33058759\nPhenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACB were set to Complete\nMode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACB was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T09:55:09.472486+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.180","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACB was added\ngene: PRKACB was added to Polydactyly. Sources: Literature\nMode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACB were set to 33058759\nPhenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACB were set to Complete\nMode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACB was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T09:54:30.884680+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.180","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACA was added\ngene: PRKACA was added to Polydactyly. Sources: Literature\nMode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACA were set to 33058759; 31130284\nPhenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACA were set to Complete\nMode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: PRKACA was set to GREEN\nAdded comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).\r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACA","entity_type":"gene"},{"created":"2020-10-25T09:50:58.791897+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"edited their review of gene: PRKACB: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T09:49:12.465308+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PRKACB was added\ngene: PRKACB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRKACB were set to 33058759\nPhenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability\nPenetrance for gene: PRKACB were set to Complete\nReview for gene: PRKACB was set to AMBER\nAdded comment: ID was a feature in 2/4 individuals with PRKACB pathogenic variant reported to date.\r\n------\r\nPalencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.\r\n\r\nThe most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.\r\n\r\nOther variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.\r\n\r\nIntellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.\r\n\r\nAs the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.\r\n\r\nWES was carried out in all.\r\n\r\nPRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).\r\n\r\nPRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.\r\n\r\nProtein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.\r\n\r\nThe authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).  \r\n\r\nBy performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors  demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.\r\n\r\nAs for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). \nSources: Literature","entity_name":"PRKACB","entity_type":"gene"},{"created":"2020-10-25T09:15:57.364103+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.180","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: SHANK3 was added\ngene: SHANK3 was added to Regression. Sources: Literature\nMode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SHANK3 were set to 32050889, 29719671\nPhenotypes for gene: SHANK3 were set to # 606232. PHELAN-MCDERMID SYNDROME - PHMDS\nPenetrance for gene: SHANK3 were set to Complete\nReview for gene: SHANK3 was set to GREEN\nAdded comment: Regression has been reported in several individuals with Phelan-McDermid syndrome due to SHANK3 variants or deletions encompassing this gene. \nSources: Literature","entity_name":"SHANK3","entity_type":"gene"},{"created":"2020-10-25T08:30:53.981963+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.180","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCO1 as ready","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:30:53.973427+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.180","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Red List (Low Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:30:49.592820+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.180","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from  to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:30:22.750287+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.179","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:29:49.536303+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.178","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:29:23.907409+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.177","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SCO1 as Red List (low evidence)","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:29:23.896472+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.177","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Red List (Low Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:28:56.129051+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.176","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:28:03.068088+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5102","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCO1 as ready","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:28:03.060633+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5102","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Green List (High Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:27:56.377098+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5102","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from  to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:26:30.531460+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5101","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:26:14.073839+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5100","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:25:55.863441+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5099","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:25:28.111187+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.523","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCO1 as ready","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:25:28.100285+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.523","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sco1 has been classified as Green List (High Evidence).","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:25:19.384980+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.523","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCO1 were changed from  to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:24:51.006258+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.522","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SCO1 were set to ","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:24:23.736230+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.521","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:23:55.221232+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SCO1","entity_type":"gene"},{"created":"2020-10-25T08:18:06.653723+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: COX10 as ready","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:18:06.642808+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cox10 has been classified as Green List (High Evidence).","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:18:01.762615+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3102","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: COX10 were changed from  to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:17:28.884504+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3101","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: COX10 were set to ","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:16:52.908271+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3100","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:16:21.337229+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3099","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:13:29.750671+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.176","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: COX10 as ready","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:13:29.739739+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.176","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cox10 has been classified as Green List (High Evidence).","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:13:26.694649+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.176","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: COX10 were changed from  to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:13:00.221492+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.175","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: COX10 were set to ","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:12:33.498790+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.174","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:12:03.840764+11:00","panel_name":"Regression","panel_id":206,"panel_version":"0.173","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:11:01.545457+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5099","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: COX10 as ready","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:11:01.529527+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5099","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cox10 has been classified as Green List (High Evidence).","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:10:54.760957+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5099","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: COX10 were changed from  to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:10:37.225929+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5098","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: COX10 were set to ","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:10:20.317319+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5097","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:10:01.888871+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5096","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:09:08.376455+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: COX10 as ready","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:09:08.355747+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cox10 has been classified as Green List (High Evidence).","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:09:01.909585+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.520","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: COX10 were changed from  to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:08:34.578341+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.519","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: COX10 were set to ","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:08:06.349322+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.518","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-25T08:07:36.259267+11:00","panel_name":"Mitochondrial disease","panel_id":203,"panel_version":"0.517","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"COX10","entity_type":"gene"},{"created":"2020-10-24T20:08:08.673707+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.43","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RAPSN as ready","entity_name":"RAPSN","entity_type":"gene"},{"created":"2020-10-24T20:08:08.664739+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.43","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rapsn has been classified as Green List (High Evidence).","entity_name":"RAPSN","entity_type":"gene"},{"created":"2020-10-24T20:08:05.006935+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.43","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RAPSN were set to ","entity_name":"RAPSN","entity_type":"gene"},{"created":"2020-10-24T20:07:56.213973+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Tag SV/CNV tag was added to gene: RAPSN.\nTag founder tag was added to gene: RAPSN.","entity_name":"RAPSN","entity_type":"gene"},{"created":"2020-10-24T20:07:44.403522+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 11791205, 14504330, 20930056, 25194721; Phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RAPSN","entity_type":"gene"},{"created":"2020-10-24T20:04:46.085987+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: LRP4 as ready","entity_name":"LRP4","entity_type":"gene"},{"created":"2020-10-24T20:04:46.078224+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: lrp4 has been classified as Green List (High Evidence).","entity_name":"LRP4","entity_type":"gene"},{"created":"2020-10-24T20:04:24.155552+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.42","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: LRP4 were set to ","entity_name":"LRP4","entity_type":"gene"},{"created":"2020-10-24T20:04:13.877126+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.41","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24234652, 26052878, 24200689; Phenotypes: Myasthenic syndrome, congenital, 17, MIM# 616304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"LRP4","entity_type":"gene"},{"created":"2020-10-24T19:58:32.262914+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.41","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: LAMA5 as ready","entity_name":"LAMA5","entity_type":"gene"},{"created":"2020-10-24T19:58:32.255655+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.41","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: lama5 has been classified as Red List (Low Evidence).","entity_name":"LAMA5","entity_type":"gene"},{"created":"2020-10-24T19:58:29.796934+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.41","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: LAMA5 were changed from muscle weakness, myopia, and facial tics to Presynaptic congenital myasthenic syndrome","entity_name":"LAMA5","entity_type":"gene"},{"created":"2020-10-24T19:58:19.272836+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.40","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: LAMA5 were set to 28544784","entity_name":"LAMA5","entity_type":"gene"},{"created":"2020-10-24T19:58:06.840508+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.39","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: LAMA5: Rating: RED; Mode of pathogenicity: None; Publications: 28544784, 29377152; Phenotypes: Presynaptic congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"LAMA5","entity_type":"gene"},{"created":"2020-10-24T19:55:11.135010+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.39","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: DPAGT1 as ready","entity_name":"DPAGT1","entity_type":"gene"},{"created":"2020-10-24T19:55:11.121835+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.39","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: dpagt1 has been classified as Green List (High Evidence).","entity_name":"DPAGT1","entity_type":"gene"},{"created":"2020-10-24T19:55:07.720220+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.39","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DPAGT1 were set to ","entity_name":"DPAGT1","entity_type":"gene"},{"created":"2020-10-24T19:54:49.954727+11:00","panel_name":"Congenital Myasthenia","panel_id":3078,"panel_version":"0.38","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22742743, 29356258, 28712839, 28662078; Phenotypes: Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"DPAGT1","entity_type":"gene"},{"created":"2020-10-24T19:51:30.248126+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.173","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.\r\n\r\nThe GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation.; to: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.\r\n\r\nThe GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation, suggesting this is a disorder of glycosylation. However, there is also some data put forward in PMID 30635494 that this may be a mitochondrial condition.","entity_name":"GFPT1","entity_type":"gene"},{"created":"2020-10-24T19:50:36.220452+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.173","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: GFPT1 as ready","entity_name":"GFPT1","entity_type":"gene"},{"created":"2020-10-24T19:50:36.211566+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.173","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: gfpt1 has been classified as Green List (High Evidence).","entity_name":"GFPT1","entity_type":"gene"},{"created":"2020-10-24T19:50:33.573357+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.173","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: GFPT1 were changed from  to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy","entity_name":"GFPT1","entity_type":"gene"},{"created":"2020-10-24T19:50:06.666953+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.172","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: GFPT1 were set to ","entity_name":"GFPT1","entity_type":"gene"},{"created":"2020-10-24T19:49:39.914223+11:00","panel_name":"Congenital Disorders of Glycosylation","panel_id":68,"panel_version":"0.171","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"GFPT1","entity_type":"gene"}]}