{"count":221304,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1732","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1730","results":[{"created":"2020-07-14T10:06:06.706957+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3314","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ALOX12 as Red List (low evidence)","entity_name":"ALOX12","entity_type":"gene"},{"created":"2020-07-14T10:06:06.692995+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3314","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: alox12 has been classified as Red List (Low Evidence).","entity_name":"ALOX12","entity_type":"gene"},{"created":"2020-07-14T10:05:50.401221+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3313","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ALOX12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None","entity_name":"ALOX12","entity_type":"gene"},{"created":"2020-07-14T10:01:04.010160+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3313","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ETF1 as ready","entity_name":"ETF1","entity_type":"gene"},{"created":"2020-07-14T10:01:04.003067+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3313","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: etf1 has been classified as Red List (Low Evidence).","entity_name":"ETF1","entity_type":"gene"},{"created":"2020-07-14T10:00:56.062765+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3313","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ETF1 as Red List (low evidence)","entity_name":"ETF1","entity_type":"gene"},{"created":"2020-07-14T10:00:56.053033+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3313","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: etf1 has been classified as Red List (Low Evidence).","entity_name":"ETF1","entity_type":"gene"},{"created":"2020-07-14T10:00:37.669970+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3312","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ETF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None","entity_name":"ETF1","entity_type":"gene"},{"created":"2020-07-14T09:56:19.793617+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Zornitza Stark","item_type":"entity","text":"commented on gene: TTI1: Two unrelated consanguineous families previously described with homozygous missense variants, both in large cohort papers with multiple candidate genes in inbred population. No functional evidence provided, segregation uninformative.","entity_name":"TTI1","entity_type":"gene"},{"created":"2020-07-14T09:55:56.656082+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3312","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TTI1 were changed from  to Intellectual disability","entity_name":"TTI1","entity_type":"gene"},{"created":"2020-07-14T09:55:35.281112+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3311","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TTI1 were set to ","entity_name":"TTI1","entity_type":"gene"},{"created":"2020-07-14T09:54:54.879398+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3310","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: TTI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"TTI1","entity_type":"gene"},{"created":"2020-07-14T05:30:41.765768+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: CNPY3 was added\ngene: CNPY3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CNPY3 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CNPY3 were set to 29394991; 30237576\nPhenotypes for gene: CNPY3 were set to Epileptic encephalopathy, early infantile, 60 (MIM 617929)\nPenetrance for gene: CNPY3 were set to Complete\nReview for gene: CNPY3 was set to GREEN\nAdded comment: Biallelic CNPY3 mutations cause Epileptic encephalopathy, early infantile, 60 (MIM 617929).\r\n\r\nThe phenotype including among others hypotonia, intractable seizures, DD and ID has been first reported by Mutoh et al (2018 - PMID: 29394991) in 3 subjects from 2 families. Evidence was provided for the role of the gene (incl. mouse model) and pathogenicity of the identified variants (resulting in LoF). \r\n\r\nAnother subject with similar features of hypotonia, DD, intractable epilepsy, feeding problems has been described briefly by Maddirevula et al (2019 - PMID: 30237576). \nSources: Literature","entity_name":"CNPY3","entity_type":"gene"},{"created":"2020-07-14T05:30:36.277796+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.745","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"CNPY3","entity_type":"gene"},{"created":"2020-07-14T05:25:12.926855+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: KIF21B was added\ngene: KIF21B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: KIF21B were set to 32415109\nPhenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly\nPenetrance for gene: KIF21B were set to unknown\nMode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN\nAdded comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors). \nSources: Literature","entity_name":"KIF21B","entity_type":"gene"},{"created":"2020-07-14T05:18:54.765709+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PAX1 was added\ngene: PAX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Radboud University Medical Center, Nijmegen\nMode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PAX1 were set to 29681087; 23851939; 28657137\nPhenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560\nPenetrance for gene: PAX1 were set to Complete\nReview for gene: PAX1 was set to AMBER\nAdded comment: Biallelic PAX1 pathogenic variants cause Otofaciocervical syndrome 2 (OMIM 615560).\r\n\r\nBrief review of the literature suggests 3 relevant publications to date (04-07-2020).\r\n\r\n2 individuals with DD and ID have been reported (Patil et al, 2018 - PMID: 29681087 and Pohl et al, 2013 - PMID: 23851939). Other subjects reported were only evaluated as newborns(mostly)/infants [Paganini et al, 2017 - PMID: 28657137, Patil et al, 2018 - PMID: 29681087].\r\n\r\nWhile the first report by Pohl et al identified a homozygous missense variant supported by functional studies [NM_006192.5:c.497G>T - p.(Gly166Val)] subsequent ones identified homozygosity for pLoF mutations [Patil et al: NM_006192.4:c.1173_1174insGCCCG / Paganini et al: NM_006192:c.1104C>A - p.(Cys368*)].\r\n\r\nAs discussed by Pohl et al:\r\n\r\nPAX1 encodes a transcription factor with critical role in pattern formation during embryogenesis. Study of the mouse Gly157Val (equivalent to human Gly166Val) Pax1 variant suggested reduced binding affinity (reduced transactivation of a regulatory sequence of the Nkx3-2 promoter) and hypofunctional nature of this variant.\r\n\r\nMouse models seem to recapitulate features of the disorder (skeletal, immunodeficiency) while the role of Pax1 in hearing process was thought to be supported by early expression (P6) in mouse cochlea. \r\n\r\nOverall this gene can be considered for inclusion in the ID panel with amber/green rating. \nSources: Literature, Radboud University Medical Center, Nijmegen","entity_name":"PAX1","entity_type":"gene"},{"created":"2020-07-14T05:12:31.861199+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: TMEM106B was added\ngene: TMEM106B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: TMEM106B were set to 29186371; 29444210; 32595021\nPhenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)\nPenetrance for gene: TMEM106B were set to Complete\nMode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to GREEN\nAdded comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 -  PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021). \r\n\r\nWhile a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].\r\n\r\nAll harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).\r\n\r\nAs discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.\r\n\r\nRecurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.  \r\n\r\nGenes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.\r\n\r\nOverall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating. \nSources: Literature","entity_name":"TMEM106B","entity_type":"gene"},{"created":"2020-07-14T05:12:27.627874+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.745","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: TMEM106B was added\ngene: TMEM106B was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: TMEM106B were set to 29186371; 29444210; 32595021\nPhenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)\nPenetrance for gene: TMEM106B were set to Complete\nMode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to AMBER\nAdded comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 -  PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021). \r\n\r\nWhile a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].\r\n\r\nAll harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).\r\n\r\nAs discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.\r\n\r\nRecurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.  \r\n\r\nGenes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.\r\n\r\nOverall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating. \nSources: Literature","entity_name":"TMEM106B","entity_type":"gene"},{"created":"2020-07-14T05:01:19.751584+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.745","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: TBC1D2B was added\ngene: TBC1D2B was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TBC1D2B were set to 32623794\nPhenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality\nPenetrance for gene: TBC1D2B were set to Complete\nReview for gene: TBC1D2B was set to GREEN\nAdded comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. \r\n\r\nFeatures included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. \r\n\r\nAll were born to non-consanguineous couples and additional investigations were performed in some. \r\n\r\nVariants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. \r\n\r\nIn line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. \r\n\r\nTBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. \r\n\r\nGenes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. \r\n\r\nOverall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel. \nSources: Literature","entity_name":"TBC1D2B","entity_type":"gene"},{"created":"2020-07-14T04:59:24.545333+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: TBC1D2B was added\ngene: TBC1D2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TBC1D2B were set to 32623794\nPhenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality\nPenetrance for gene: TBC1D2B were set to Complete\nReview for gene: TBC1D2B was set to AMBER\nAdded comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. \r\n\r\nFeatures included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. \r\n\r\nAll were born to non-consanguineous couples and additional investigations were performed in some. \r\n\r\nVariants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. \r\n\r\nIn line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. \r\n\r\nTBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. \r\n\r\nGenes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. \r\n\r\nOverall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel. \nSources: Literature","entity_name":"TBC1D2B","entity_type":"gene"},{"created":"2020-07-14T04:46:59.579610+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: EXOC2 was added\ngene: EXOC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: EXOC2 were set to 32639540\nPhenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology\nPenetrance for gene: EXOC2 were set to Complete\nReview for gene: EXOC2 was set to AMBER\nAdded comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. \r\n\r\nClinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). \r\n\r\nPrevious investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. \r\n\r\nEXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. \r\n\r\nAffected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. \r\n\r\nAn exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2.\r\n\r\nMutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome).\r\n\r\nThe authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants). \nSources: Literature","entity_name":"EXOC2","entity_type":"gene"},{"created":"2020-07-14T04:37:28.808231+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: CEP120 was added\ngene: CEP120 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CEP120 were set to 27208211\nPhenotypes for gene: CEP120 were set to Joubert syndrome 31 (MIM 617761); Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300)\nPenetrance for gene: CEP120 were set to Complete\nReview for gene: CEP120 was set to GREEN\nAdded comment: Pathogenic CEP120 variants have been reported in recessive ciliopathies, namely Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) and Joubert syndrome 31 (MIM 617761). \r\n\r\nThe former is associated with a severe/lethal outcome (4 unrelated infants described by Shaheen et al 2015 - PMID: 25361962, 2 fetuses reported by Roosing et al 2016 - PMID: 27208211). \r\n\r\nRoosing et al however, also provided details on 4 unrelated subjects with Joubert syndrome diagnosis. All presented with a neurologic phenotype of hypotonia, DD, cognitive impairment and exhibited a molar tooth sign.\r\n\r\nAs a result, this gene can be considered for inclusion in the ID panel with green rating (>3 individuals/variants, consistent ciliopathy phenotype). \nSources: Literature","entity_name":"CEP120","entity_type":"gene"},{"created":"2020-07-14T04:33:07.131365+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: CCDC174 was added\ngene: CCDC174 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CCDC174 were set to 26358778\nPhenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816\nPenetrance for gene: CCDC174 were set to Complete\nMode of pathogenicity for gene: CCDC174 was set to Other\nReview for gene: CCDC174 was set to AMBER\nAdded comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816).\r\n\r\nVolodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. \r\n\r\nOverall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports. \nSources: Literature","entity_name":"CCDC174","entity_type":"gene"},{"created":"2020-07-14T04:29:03.465356+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: ACOX2 was added\ngene: ACOX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ACOX2 were set to 27647924; 27884763; 29287774\nPhenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6 - 617308\nPenetrance for gene: ACOX2 were set to unknown\nReview for gene: ACOX2 was set to RED\nAdded comment: Biallelic pathogenic ACOX2 variants cause Bile acid synthesis defect, congenital, 6 (MIM 617308). Overall the phenotype corresponds to an IEM/peroxisomal disorder.\r\n\r\nAs per 01-07-2020 there are 3 reports, briefly reviewed :\r\n\r\n- Vilarinho et al [2016 - PMID: 27647924] provided details on an 8-year-old boy with ID.\r\n- Monte et al [2017 - PMID: 27884763] described a 16 year old male with sustained elevation of transaminases *without* accompanying neurologic symptomatology (as they comment).\r\n- Ferdinandusse et al [2018 - PMID: 29287774] reported on a girl deceased at the age of few months.\r\n\r\nPlease consider inclusion in the ID panel with amber/red rating pending further reports. \nSources: Literature","entity_name":"ACOX2","entity_type":"gene"},{"created":"2020-07-14T04:22:48.043463+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.745","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: ABCA2 was added\ngene: ABCA2 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ABCA2 were set to 30237576; 29302074; 31047799\nPhenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808\nPenetrance for gene: ABCA2 were set to Complete\nReview for gene: ABCA2 was set to GREEN\nAdded comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). \r\n\r\nThere are 3 relevant publications (01-07-2020) :\r\n- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.\r\n- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.\r\n- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.\r\n\r\nAll subjects harbored biallelic pLoF variants.\r\n\r\nN.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.\r\n\r\nOverall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). \nSources: Literature","entity_name":"ABCA2","entity_type":"gene"},{"created":"2020-07-14T04:20:57.951032+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: ABCA2 was added\ngene: ABCA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ABCA2 were set to 30237576; 29302074; 31047799\nPhenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808\nPenetrance for gene: ABCA2 were set to Complete\nReview for gene: ABCA2 was set to GREEN\nAdded comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). \r\n\r\nThere are 3 relevant publications (01-07-2020) :\r\n- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.\r\n- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.\r\n- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.\r\n\r\nAll subjects harbored biallelic pLoF variants.\r\n\r\nN.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.\r\n\r\nOverall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). \nSources: Literature","entity_name":"ABCA2","entity_type":"gene"},{"created":"2020-07-14T04:08:46.759024+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.745","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: HERC2 was added\ngene: HERC2 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: HERC2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: HERC2 were set to 23065719; 23243086; 30902390; 32571899; 27848944; 26077850; 27759030\nPhenotypes for gene: HERC2 were set to Mental retardation, autosomal recessive 38 (MIM 615516)\nPenetrance for gene: HERC2 were set to Complete\nReview for gene: HERC2 was set to GREEN\nAdded comment: Biallelic pathogenic HERC2 variants cause Mental retardation, autosomal recessive 38 (MIM 615516). \r\n\r\nThe current review is based mostly on the information provided by Elpidorou et al (2020 - PMID: 32571899) summarizing the findings in several affected individuals as published in the literature. ID was a universal feature among them (27/27) and seizures were reported in some (9/27):\r\n- 22 subjects from Amish/Mennonite families were homozygous for p.Pro594Leu [NM_004667.5(HERC2):c.1781C>T] (Puffenberger et al 2012 - PMID: 23065719, Harlalka et al 2013 - PMID: 23243086, Abraham et al - PMID: 30902390)\r\n- 2 additional patients were homozygous for another missense SNV [NM_004667.5(HERC2):c.4625G>A - p.Arg1542His] (Abraham et al 2019 - PMID: 30902390)\r\n- 3 sibs born to consanguineous parents, homozygous for NM_004667.5:c.13767_13770delTGAA - p.(Asn4589LysTer4598)] as described by Elpidorou et al. \r\n- 1 male homozygous 286 kb deletion spanning several 5' exons of HERC2 as well as the first exons of OCA2 was described by Morice-Picard et al (2016 - PMID: 27759030). Despite a neurological presentation (axial hypotonia, peripheral hypertonia, extrapyramidal symptoms and uncoordinated movements) further information was not available.\r\n\r\nApart from the cases summarized by Elpidorou et al, there have been few additional ones e.g. :\r\n- Trujillano et al (2017 - PMID: 27848944) reported briefly on a patient, homozygous for NM_004667.5:c.4676-1G>A displaying seizures, hypotonia, global DD, \"Encephalopathy\" and abnormality of the liver.\r\n- Yavarna et al (2015 - PMID: 26077850) provided few details with on an individual with primarily 'neurocognitive' phenotype but rather atypical presentation (MRI abnormalities, TGA, VSD, renal anomaly, growth retardation, hearing loss) due to p.Q3164X variant (recessive inheritance was specified). \r\n\r\nSeveral lines of evidence support an important role for the protein encoded (an E3 ubiquitin protein ligase, interacting also with UBE3A, involved in several cellular processes incl. cell cycle regulation, spindle formation during mitosis, mitochondrial functions, DNA damage responses by targeting proteins such as XPA) as well as the effect of the reported variants (mRNA studies, Western blot, detection of a fusion transcript in the case of the deletion, etc). \r\n\r\nIndividuals from the Amish families displayed Angelman-like features (in line with HERC2-UBE3A interaction) with - among others - gait instability. Mouse models recapitulate some of these features (e.g. the movement disorder) as extensively discussed by Abraham et al.\r\n\r\nOverall this gene can be included in the ID and epilepsy panels with green rating. \nSources: Literature","entity_name":"HERC2","entity_type":"gene"},{"created":"2020-07-14T04:07:11.444320+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"HERC2","entity_type":"gene"},{"created":"2020-07-13T18:50:32.427735+10:00","panel_name":"Aortopathy_Connective Tissue Disorders","panel_id":44,"panel_version":"0.160","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PTDSS1 as ready","entity_name":"PTDSS1","entity_type":"gene"},{"created":"2020-07-13T18:50:32.407990+10:00","panel_name":"Aortopathy_Connective Tissue Disorders","panel_id":44,"panel_version":"0.160","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ptdss1 has been classified as Green List (High Evidence).","entity_name":"PTDSS1","entity_type":"gene"},{"created":"2020-07-13T18:49:28.056563+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.69","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: PCSK1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:44.199757+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.69","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PCSK1 as ready","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:44.185850+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.69","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pcsk1 has been classified as Amber List (Moderate Evidence).","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:42.183640+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.69","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PCSK1 were changed from  to Obesity with impaired prohormone processing (MIM#600955)","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:25.804952+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.68","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: PCSK1 were set to ","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:04.595973+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PCSK1 as Amber List (moderate evidence)","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:48:04.584951+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pcsk1 has been classified as Amber List (Moderate Evidence).","entity_name":"PCSK1","entity_type":"gene"},{"created":"2020-07-13T18:45:18.299677+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.66","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PROK2 as ready","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:45:18.294831+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.66","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: Evidence supporting association between bi-allelic variants causing IHH is stronger than for mono-allelic disease.","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:45:18.261514+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.66","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: prok2 has been classified as Green List (High Evidence).","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:44:39.777570+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.66","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PROK2 were changed from  to Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628)","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:44:22.416753+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.65","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: PROK2 were set to ","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:43:49.999063+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.64","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: PROK2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"PROK2","entity_type":"gene"},{"created":"2020-07-13T18:42:36.546768+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.63","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PROP1 as ready","entity_name":"PROP1","entity_type":"gene"},{"created":"2020-07-13T18:42:36.539393+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.63","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: prop1 has been classified as Green List (High Evidence).","entity_name":"PROP1","entity_type":"gene"},{"created":"2020-07-13T18:42:33.507772+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.63","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PROP1 were changed from  to Pituitary hormone deficiency, combined, 2 (MIM#262600)","entity_name":"PROP1","entity_type":"gene"},{"created":"2020-07-13T18:42:06.166548+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.62","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: PROP1 were set to ","entity_name":"PROP1","entity_type":"gene"},{"created":"2020-07-13T18:41:45.881791+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.61","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PROP1","entity_type":"gene"},{"created":"2020-07-13T18:41:00.804137+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RPL10 as ready","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:41:00.796520+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rpl10 has been classified as Green List (High Evidence).","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:40:56.837949+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2750","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RPL10 were changed from  to Mental retardation, X-linked, syndromic, 35 (MIM#300998)","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:40:32.795190+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2749","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RPL10 were set to ","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:40:07.491181+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.2748","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:39:25.286634+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.60","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RPL10 as ready","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:39:25.256851+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.60","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rpl10 has been classified as Green List (High Evidence).","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:39:21.332796+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.60","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RPL10 as Green List (high evidence)","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:39:21.325588+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.60","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rpl10 has been classified as Green List (High Evidence).","entity_name":"RPL10","entity_type":"gene"},{"created":"2020-07-13T18:38:29.522605+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.59","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SAMD9 as ready","entity_name":"SAMD9","entity_type":"gene"},{"created":"2020-07-13T18:38:29.512803+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.59","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: samd9 has been classified as Green List (High Evidence).","entity_name":"SAMD9","entity_type":"gene"},{"created":"2020-07-13T18:38:24.617208+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.59","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SAMD9 as Green List (high evidence)","entity_name":"SAMD9","entity_type":"gene"},{"created":"2020-07-13T18:38:24.610397+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.59","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: samd9 has been classified as Green List (High Evidence).","entity_name":"SAMD9","entity_type":"gene"},{"created":"2020-07-13T18:37:17.647086+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.58","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SEMA3E as ready","entity_name":"SEMA3E","entity_type":"gene"},{"created":"2020-07-13T18:37:17.640368+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.58","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sema3e has been classified as Red List (Low Evidence).","entity_name":"SEMA3E","entity_type":"gene"},{"created":"2020-07-13T18:37:13.566856+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.58","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SEMA3E as Red List (low evidence)","entity_name":"SEMA3E","entity_type":"gene"},{"created":"2020-07-13T18:37:13.560918+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.58","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sema3e has been classified as Red List (Low Evidence).","entity_name":"SEMA3E","entity_type":"gene"},{"created":"2020-07-13T18:36:38.564092+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.57","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SGPL1 as ready","entity_name":"SGPL1","entity_type":"gene"},{"created":"2020-07-13T18:36:38.553576+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.57","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sgpl1 has been classified as Green List (High Evidence).","entity_name":"SGPL1","entity_type":"gene"},{"created":"2020-07-13T18:36:35.189626+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.57","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SGPL1 as Green List (high evidence)","entity_name":"SGPL1","entity_type":"gene"},{"created":"2020-07-13T18:36:35.179886+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.57","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sgpl1 has been classified as Green List (High Evidence).","entity_name":"SGPL1","entity_type":"gene"},{"created":"2020-07-13T18:35:58.730003+10:00","panel_name":"Deafness","panel_id":209,"panel_version":"0.365","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SOX10 as ready","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:35:58.717334+10:00","panel_name":"Deafness","panel_id":209,"panel_version":"0.365","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox10 has been classified as Green List (High Evidence).","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:35:56.375577+10:00","panel_name":"Deafness","panel_id":209,"panel_version":"0.365","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SOX10 were changed from  to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:35:36.331157+10:00","panel_name":"Deafness","panel_id":209,"panel_version":"0.364","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SOX10 were set to ","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:35:14.408557+10:00","panel_name":"Deafness","panel_id":209,"panel_version":"0.363","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SOX10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:34:33.356844+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.56","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SOX10 as ready","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:34:33.348994+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.56","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox10 has been classified as Green List (High Evidence).","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:34:30.454570+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.56","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SOX10 were changed from PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266) to Kallman syndrome; PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:33:23.109365+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.55","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SOX10 as Green List (high evidence)","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:33:23.102328+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.55","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox10 has been classified as Green List (High Evidence).","entity_name":"SOX10","entity_type":"gene"},{"created":"2020-07-13T18:32:28.056832+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.54","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TAC3 as ready","entity_name":"TAC3","entity_type":"gene"},{"created":"2020-07-13T18:32:28.049626+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.54","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tac3 has been classified as Green List (High Evidence).","entity_name":"TAC3","entity_type":"gene"},{"created":"2020-07-13T18:31:56.575915+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.54","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TAC3 were changed from  to Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839)","entity_name":"TAC3","entity_type":"gene"},{"created":"2020-07-13T18:31:17.917546+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.53","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TAC3 were set to ","entity_name":"TAC3","entity_type":"gene"},{"created":"2020-07-13T18:30:50.181295+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.52","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: TAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"TAC3","entity_type":"gene"},{"created":"2020-07-13T18:29:43.002355+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.51","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TOE1 as ready","entity_name":"TOE1","entity_type":"gene"},{"created":"2020-07-13T18:29:42.985960+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.51","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: toe1 has been classified as Green List (High Evidence).","entity_name":"TOE1","entity_type":"gene"},{"created":"2020-07-13T18:29:38.560987+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.51","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TOE1 as Green List (high evidence)","entity_name":"TOE1","entity_type":"gene"},{"created":"2020-07-13T18:29:38.553910+10:00","panel_name":"Disorders of Sex Differentiation","panel_id":99,"panel_version":"0.51","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: toe1 has been classified as Green List (High Evidence).","entity_name":"TOE1","entity_type":"gene"},{"created":"2020-07-13T18:16:28.667575+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3309","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: SGMS2 as ready","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:16:28.660689+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3309","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgms2 has been classified as Green List (High Evidence).","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:16:17.086112+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3309","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: SGMS2 as Green List (high evidence)","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:16:17.076740+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3309","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgms2 has been classified as Green List (High Evidence).","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:15:54.673119+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.3308","user_name":"Bryony Thompson","item_type":"entity","text":"gene: SGMS2 was added\ngene: SGMS2 was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SGMS2 were set to 30779713; 32028018\nPhenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550\nReview for gene: SGMS2 was set to GREEN\nAdded comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. \nSources: Expert list","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:14:59.752757+10:00","panel_name":"Osteopetrosis","panel_id":150,"panel_version":"0.3","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: SGMS2 as ready","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:14:59.746085+10:00","panel_name":"Osteopetrosis","panel_id":150,"panel_version":"0.3","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgms2 has been classified as Green List (High Evidence).","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:14:39.780236+10:00","panel_name":"Osteopetrosis","panel_id":150,"panel_version":"0.3","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: SGMS2 as Green List (high evidence)","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:14:39.773447+10:00","panel_name":"Osteopetrosis","panel_id":150,"panel_version":"0.3","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgms2 has been classified as Green List (High Evidence).","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:13:40.636647+10:00","panel_name":"Osteopetrosis","panel_id":150,"panel_version":"0.2","user_name":"Bryony Thompson","item_type":"entity","text":"gene: SGMS2 was added\ngene: SGMS2 was added to Osteopetrosis. Sources: Literature\nMode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SGMS2 were set to 30779713; 32028018\nPhenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550\nReview for gene: SGMS2 was set to GREEN\nAdded comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. \nSources: Literature","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:10:43.718269+10:00","panel_name":"Osteogenesis Imperfecta","panel_id":147,"panel_version":"0.26","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: SGMS2 as ready","entity_name":"SGMS2","entity_type":"gene"},{"created":"2020-07-13T18:10:43.709893+10:00","panel_name":"Osteogenesis Imperfecta","panel_id":147,"panel_version":"0.26","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgms2 has been classified as Green List (High Evidence).","entity_name":"SGMS2","entity_type":"gene"}]}