{"count":220725,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=151","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=149","results":[{"created":"2025-10-11T18:34:08.148398+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3369","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TRIM49 as Amber List (moderate evidence)","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:34:08.136747+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3369","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: trim49 has been classified as Amber List (Moderate Evidence).","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:33:52.999857+11:00","panel_name":"Retinitis pigmentosa_Autosomal Recessive/X-linked","panel_id":277,"panel_version":"0.179","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TRIM49 as Amber List (moderate evidence)","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:33:52.988537+11:00","panel_name":"Retinitis pigmentosa_Autosomal Recessive/X-linked","panel_id":277,"panel_version":"0.179","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: trim49 has been classified as Amber List (Moderate Evidence).","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:33:41.866855+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3368","user_name":"Bryony Thompson","item_type":"entity","text":"changed review comment from: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families. \nSources: Literature; to: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not. This constitutes convincing functional evidence for pathogenicity in two families. \r\nSources: Literature","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:33:30.063334+11:00","panel_name":"Retinitis pigmentosa_Autosomal Recessive/X-linked","panel_id":277,"panel_version":"0.178","user_name":"Bryony Thompson","item_type":"entity","text":"gene: TRIM49 was added\ngene: TRIM49 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature\nMode of inheritance for gene: TRIM49 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRIM49 were set to 40956390\nPhenotypes for gene: TRIM49 were set to retinitis pigmentosa MONDO:0019200\nReview for gene: TRIM49 was set to AMBER\nAdded comment: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not. This constitutes convincing functional evidence for pathogenicity in two families. \nSources: Literature","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T18:33:19.329561+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3368","user_name":"Bryony Thompson","item_type":"entity","text":"gene: TRIM49 was added\ngene: TRIM49 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: TRIM49 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TRIM49 were set to 40956390\nPhenotypes for gene: TRIM49 were set to retinitis pigmentosa MONDO:0019200\nReview for gene: TRIM49 was set to AMBER\nAdded comment: Two unrelated families (consanguineous marriage in Family 2; possible maternal uniparental disomy in Family 1) carry rare biallelic TRIM49 variants (c.1184C>A and c.1134_1137delTCTT) that are absent from 7 283 in‑house controls and have extremely low gnomAD frequencies. Functional experiments in human RPE cell lines demonstrate that loss of TRIM49 impairs autophagic flux, ULK1 expression and POS phagocytosis, and that overexpression of wild‑type TRIM49 rescues these defects whereas mutant TRIM49 (M1/M2) does not (Box 438, Box 440, Box 439). This constitutes convincing functional evidence for pathogenicity in two families. \nSources: Literature","entity_name":"TRIM49","entity_type":"gene"},{"created":"2025-10-11T16:46:55.412511+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3367","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: PCDHA9 as ready","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T16:46:55.404389+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3367","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: pcdha9 has been classified as Red List (Low Evidence).","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T16:46:46.933358+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3367","user_name":"Bryony Thompson","item_type":"entity","text":"gene: PCDHA9 was added\ngene: PCDHA9 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PCDHA9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PCDHA9 were set to 29477871; 40988636\nPhenotypes for gene: PCDHA9 were set to Hirschsprung disease MONDO:0018309; root resorption MONDO:0001997\nReview for gene: PCDHA9 was set to RED\nAdded comment: Single publication reporting an association with Hirschsprung disease, including a missense in a family (p.Gly572Arg) that is too common in gnomAD to be associated with disease and 2 rare missense in 2 sporadic cases. Knockdown in a cell line increased proliferation and\r\nmigration, but suppressed apoptosis. A single publication with a single missense reported in association with short root anomaly. \nSources: Literature","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:58:00.180193+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.349","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: PCDHA9 as ready","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:58:00.172074+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.349","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: pcdha9 has been classified as Amber List (Moderate Evidence).","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:50.464459+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.349","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: PCDHA9 as Amber List (moderate evidence)","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:50.457103+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.349","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: pcdha9 has been classified as Amber List (Moderate Evidence).","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:25.213413+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.38","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: PCDHA9 as ready","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:25.206552+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.38","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: pcdha9 has been classified as Amber List (Moderate Evidence).","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:07.595737+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.38","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: PCDHA9 as Amber List (moderate evidence)","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:57:07.584811+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.38","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: pcdha9 has been classified as Amber List (Moderate Evidence).","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:55:50.724598+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.348","user_name":"Bryony Thompson","item_type":"entity","text":"gene: PCDHA9 was added\ngene: PCDHA9 was added to Incidentalome. Sources: Literature\nMode of inheritance for gene: PCDHA9 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PCDHA9 were set to 38467605\nPhenotypes for gene: PCDHA9 were set to amyotrophic lateral sclerosis MONDO:0004976\nReview for gene: PCDHA9 was set to AMBER\nAdded comment: Three unrelated families (one consanguineous and 2 living in close proximity) carry a homozygous c.2099T>C (p.Leu700Pro) missense variant in the transmembrane domain of PCDHA9; detailed clinical data: age at onset 36‑42 yr, limb weakness, UMN/LMN signs, EMG abnormalities, disease duration <4 yr; the variant is rare (gnomAD East Asian MAF≈0.00022, no homozygotes) and absent in 392 ALS controls; functional studies (mouse knock‑in and deletion models, HEK293 protein‑stability assays) demonstrate loss‑of‑function effects supporting pathogenicity. \nSources: Literature","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-11T14:55:50.719750+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.37","user_name":"Bryony Thompson","item_type":"entity","text":"gene: PCDHA9 was added\ngene: PCDHA9 was added to Motor Neurone Disease. Sources: Literature\nMode of inheritance for gene: PCDHA9 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PCDHA9 were set to 38467605\nPhenotypes for gene: PCDHA9 were set to amyotrophic lateral sclerosis MONDO:0004976\nReview for gene: PCDHA9 was set to AMBER\nAdded comment: Three unrelated families (one consanguineous and 2 living in close proximity) carry a homozygous c.2099T>C (p.Leu700Pro) missense variant in the transmembrane domain of PCDHA9; detailed clinical data: age at onset 36‑42 yr, limb weakness, UMN/LMN signs, EMG abnormalities, disease duration <4 yr; the variant is rare (gnomAD East Asian MAF≈0.00022, no homozygotes) and absent in 392 ALS controls; functional studies (mouse knock‑in and deletion models, HEK293 protein‑stability assays) demonstrate loss‑of‑function effects supporting pathogenicity. \nSources: Literature","entity_name":"PCDHA9","entity_type":"gene"},{"created":"2025-10-10T17:06:04.309715+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.242","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNU6ATAC as Red List (low evidence)","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:06:04.298268+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.242","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnu6atac has been classified as Red List (Low Evidence).","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:03:29.237594+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3366","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RNU6ATAC as ready","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:03:29.231008+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3366","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnu6atac has been classified as Red List (Low Evidence).","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:03:18.436608+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3366","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNU6ATAC as Red List (low evidence)","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:03:18.429114+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3366","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnu6atac has been classified as Red List (Low Evidence).","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:02:56.611097+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.346","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RNU6ATAC as ready","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:02:56.602970+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.346","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnu6atac has been classified as Red List (Low Evidence).","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:02:52.113464+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.346","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNU6ATAC as Red List (low evidence)","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:02:52.101232+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.346","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnu6atac has been classified as Red List (Low Evidence).","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:02:26.456287+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.345","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RNU6ATAC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T17:00:04.583668+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3365","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: HYPK were set to Clinical Genetics Early View","entity_name":"HYPK","entity_type":"gene"},{"created":"2025-10-10T16:59:24.915453+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.352","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: HYPK were set to Clinical Genetics Early View","entity_name":"HYPK","entity_type":"gene"},{"created":"2025-10-10T16:57:44.986299+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3364","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None","entity_name":"DNAH14","entity_type":"gene"},{"created":"2025-10-10T16:53:31.229905+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3364","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TLN1 were set to 30888838; 35861643","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T16:52:47.121593+11:00","panel_name":"Bleeding and Platelet Disorders","panel_id":54,"panel_version":"1.62","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TLN1 were set to 35861643","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T16:52:18.188135+11:00","panel_name":"Bleeding and Platelet Disorders","panel_id":54,"panel_version":"1.61","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TLN1 as Amber List (moderate evidence)","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T16:52:18.176269+11:00","panel_name":"Bleeding and Platelet Disorders","panel_id":54,"panel_version":"1.61","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tln1 has been classified as Amber List (Moderate Evidence).","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T16:51:00.478916+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3363","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: BCAT1 as ready","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:51:00.467613+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3363","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: bcat1 has been classified as Red List (Low Evidence).","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:52.372299+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3363","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: BCAT1 as Red List (low evidence)","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:52.365229+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3363","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: bcat1 has been classified as Red List (Low Evidence).","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:33.212412+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.351","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: BCAT1 as ready","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:33.194361+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.351","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: bcat1 has been classified as Red List (Low Evidence).","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:26.234037+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.351","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: BCAT1 as Red List (low evidence)","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:50:26.223107+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.351","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: bcat1 has been classified as Red List (Low Evidence).","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:47:27.906975+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Lucy Spencer","item_type":"entity","text":"gene: BCAT1 was added\ngene: BCAT1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: BCAT1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: BCAT1 were set to 41029903\nPhenotypes for gene: BCAT1 were set to Neurodevelopmental disorder (MONDO:0700092), BCAT1-related\nReview for gene: BCAT1 was set to RED\nAdded comment: PMID: 41029903 One patient with a suspected neurometabolic disorder; congenital blindness and suspected Leber Congenital Amaurosis, microcephaly, failure to thrive, profound global developmental delay and extensive delayed myelination on MRI. AT 10 he was non-verbal and non-ambulatory with regression of motor skills and -3SD for height and weight. Compound heterozygous for Phe264Leu (539 hets but no homs in gnomad v4)  and Glu348Lys (over 8000 hets and 24 homs in gnomad v4).\r\n\r\nin compound heterozygous iPSCs a severe 75% reduction in BCAT1 protein levels was seen, but mRNA levels were normal suggesting the variants affect protein stability or increased degradation. \nSources: Literature","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:44:49.287560+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"gene: BCAT1 was added\ngene: BCAT1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: BCAT1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: BCAT1 were set to 41029903\nPhenotypes for gene: BCAT1 were set to Neurodevelopmental disorder (MONDO:0700092), BCAT1-related\nReview for gene: BCAT1 was set to RED\nAdded comment: PMID: 41029903 One patient with a suspected neurometabolic disorder; congenital blindness and suspected Leber Congenital Amaurosis, microcephaly, failure to thrive, profound global developmental delay and extensive delayed myelination on MRI. AT 10 he was non-verbal and non-ambulatory with regression of motor skills and -3SD for height and weight. Compound heterozygous for Phe264Leu (539 hets but no homs in gnomad v4)  and Glu348Lys (over 8000 hets and 24 homs in gnomad v4).\r\n\r\nin compound heterozygous iPSCs a severe 75% reduction in BCAT1 protein levels was seen, but mRNA levels were normal suggesting the variants affect protein stability or increased degradation. \nSources: Literature","entity_name":"BCAT1","entity_type":"gene"},{"created":"2025-10-10T16:17:27.554541+11:00","panel_name":"Bleeding and Platelet Disorders","panel_id":54,"panel_version":"1.60","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: TLN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 40960860; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T16:16:08.389872+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"edited their review of gene: TLN1: Added comment: PMID: 40960860 de novo L353F identified in a patient with increased nuchal translucency, leukopenia, thrombocytopenia, congenital cataracts, multiple episodes of acute bronchitis, skin lesions and swelling after exercise in cold weather. Overlapping authors with PMID: 35861643, and they are postulating this is a 2nd case of the condition reported there. Some functional studies showing decreased thermal stability, has slower cellular migration and that it was slightly more aggregation-prone than WT.\r\n\r\nShared symptoms between both patients; leukopenia, thrombocytopenia, congenital cataract, and recurring episodes of acute bronchitis. Both mutations situated in the talin-1 head F2F3 domains and both have been shown to have defects in cellular migration and integrin activation.; Changed rating: AMBER; Changed publications: 40960860; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T15:54:41.188977+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: TLN1: Rating: RED; Mode of pathogenicity: None; Publications: 39704176; Phenotypes: Capillary leak syndrome MONDO:0001956, TLN1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown","entity_name":"TLN1","entity_type":"gene"},{"created":"2025-10-10T14:19:52.531711+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: DNAH14: Rating: AMBER; Mode of pathogenicity: None; Publications: 36344539, 41002930; Phenotypes: Neurodevelopmental disorder MONDO:0700092, DNAH14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"DNAH14","entity_type":"gene"},{"created":"2025-10-10T14:19:50.023051+11:00","panel_name":"Transplant Co-Morbidity","panel_id":4126,"panel_version":"0.20","user_name":"Bryony Thompson","item_type":"panel","text":"Panel name changed from Transplant Co-Morbidity Superpanel to Transplant Co-Morbidity","entity_name":null,"entity_type":null},{"created":"2025-10-10T14:06:21.065038+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: HYPK: Rating: ; Mode of pathogenicity: None; Publications: 40986405; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, HYPK-related; Mode of inheritance: None","entity_name":"HYPK","entity_type":"gene"},{"created":"2025-10-10T14:05:48.774207+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: HYPK: Rating: ; Mode of pathogenicity: None; Publications: 40986405; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, HYPK-related; Mode of inheritance: None","entity_name":"HYPK","entity_type":"gene"},{"created":"2025-10-10T13:56:42.331108+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.345","user_name":"Lucy Spencer","item_type":"entity","text":"gene: RNU6ATAC was added\ngene: RNU6ATAC was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RNU6ATAC were set to 40975062\nPhenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related\nReview for gene: RNU6ATAC was set to AMBER\nAdded comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC. \nSources: Literature","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T13:55:56.336541+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.241","user_name":"Lucy Spencer","item_type":"entity","text":"gene: RNU6ATAC was added\ngene: RNU6ATAC was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RNU6ATAC were set to 40975062\nPhenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related\nReview for gene: RNU6ATAC was set to RED\nAdded comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC. \nSources: Literature","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T13:55:17.541703+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Lucy Spencer","item_type":"entity","text":"gene: RNU6ATAC was added\ngene: RNU6ATAC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RNU6ATAC were set to 40975062\nPhenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related\nReview for gene: RNU6ATAC was set to RED\nAdded comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC. \nSources: Literature","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T13:53:28.447061+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"gene: RNU6ATAC was added\ngene: RNU6ATAC was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RNU6ATAC were set to 40975062\nPhenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related\nReview for gene: RNU6ATAC was set to RED\nAdded comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC. \nSources: Literature","entity_name":"RNU6ATAC","entity_type":"gene"},{"created":"2025-10-10T12:02:32.952692+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"gene: NFXL1 was added\ngene: NFXL1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: NFXL1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NFXL1 were set to 40430072; 41024252\nPhenotypes for gene: NFXL1 were set to Syndromic disease (MONDO:0002254), NFXL1-related\nReview for gene: NFXL1 was set to AMBER\nAdded comment: PMID: 40430072 2 siblings with psychosis and schizophrenia, homozygous for Cys441Tyr. Some modelling suggested a deleterious affect but no functional studies performed. \r\n\r\nPMID: 41024252 8 patients from 7 families with joint hyperlaxity, with or without short stature and renal disease. 6 families were homozygous for p.(Cys539Trpfs*64) while the other two were homozygous for p.(Lys681*). Paper described both as founder variants but they are rare/absent in gnomad. \r\n\r\nJoint hyperlaxity (7), chronic kidney disease/FSGS (2) small echogenic kidneys (3), acute kidney injury (1), dysmorphic features (6), short stature (6), speech delay (3).\r\n\r\nOne patient also had epilepsy, developmental delay and spasticity however c.728+1G>A in WDR45 explained this part of her phenotype. Other patients also had more severe outlying symptoms with no other explanation mentioned: 1 with developmental delay, hearing loss, brain malformations, skeletal abnormalities, and another a 3 year old who passed away following a complex medical course including blue sclera, proximal tibial fracture, severe respiratory distress due to a chest infection, and acute kidney injury. \r\n\r\nAmber given the variable phenotype findings of the reported patients and only 2 homozygous variants identified so far \nSources: Literature","entity_name":"NFXL1","entity_type":"gene"},{"created":"2025-10-10T10:54:13.366934+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.438","user_name":"Lucy Spencer","item_type":"entity","text":"gene: PTBP1 was added\ngene: PTBP1 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PTBP1 were set to 40965981\nPhenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related\nReview for gene: PTBP1 was set to GREEN\nAdded comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%). \r\n\r\nVariants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.\r\n\r\nVarious functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability. \nSources: Literature","entity_name":"PTBP1","entity_type":"gene"},{"created":"2025-10-10T10:53:31.058207+11:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.337","user_name":"Lucy Spencer","item_type":"entity","text":"gene: PTBP1 was added\ngene: PTBP1 was added to Skeletal dysplasia. Sources: Literature\nMode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PTBP1 were set to 40965981\nPhenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related\nReview for gene: PTBP1 was set to GREEN\nAdded comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%). \r\n\r\nVariants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.\r\n\r\nVarious functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability. \nSources: Literature","entity_name":"PTBP1","entity_type":"gene"},{"created":"2025-10-10T10:33:06.704138+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Lucy Spencer","item_type":"entity","text":"gene: PTBP1 was added\ngene: PTBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PTBP1 were set to 40965981\nPhenotypes for gene: PTBP1 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP1-related\nReview for gene: PTBP1 was set to GREEN\nAdded comment: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%). \r\n\r\nVariants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.\r\n\r\nVarious functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss variants also leading to increased protein stability. \nSources: Literature","entity_name":"PTBP1","entity_type":"gene"},{"created":"2025-10-10T10:31:41.206601+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"changed review comment from: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%). \r\n\r\nVarious functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss\r\nvariants also leading to increased protein stability.; to: PMID: 40965981 27 individuals with abnormal prenatal ultrasound in thirteen (48%) including short femora, IUGR, hydramnios, increased nuchal translucency, asymmetry of heart cavities, and bilateral hydronephrosis. Skeletal anomalies were seen in 24 (89%), short stature/limbs in 63%, facial dysmorphism 25 (93%), developmental delay in 78%, behavioral problems in 30% and ID in 26% generally mild/moderate, 43% had variable brain MRI abnormalities. additional features included skin, nail, and hair anomalies (52%), dental anomalies (37%), ophthalmological findings (44%), and cardiovascular defects (22%). \r\n\r\nVariants a mix of missense and startloss, and were confirmed de novo in 23/17 cases.\r\n\r\nVarious functional studies showed reduced nuclear localization and enhanced cytoplasmic retention, with start-loss\r\nvariants also leading to increased protein stability.","entity_name":"PTBP1","entity_type":"gene"},{"created":"2025-10-10T10:29:16.202249+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40965981; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), PTBP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"PTBP1","entity_type":"gene"},{"created":"2025-10-10T10:19:37.752572+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Lucy Spencer","item_type":"entity","text":"gene: PTBP2 was added\ngene: PTBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: PTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PTBP2 were set to 40965981\nPhenotypes for gene: PTBP2 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP2-related\nReview for gene: PTBP2 was set to AMBER\nAdded comment: PMID: 40965981 2 males with developmental delay, ID, autistic features. 1 had some dysmorphic features and tonic-clonic seizures. both probands had a de novo variant in PTBP2 NM_021190.4:c.2T>C (p.Met1?) and NM_021190.4:c.41G>C (p.Arg14Thr), absent from gnomad. Transfection of the variants in transfection in NIH-3T3 cells showed the missense had cytoplasmic retention and colocalization with processing bodies, and that there were 2 alternative downstream start sites Met32 and Met35 that may be used instead. \nSources: Literature","entity_name":"PTBP2","entity_type":"gene"},{"created":"2025-10-10T10:18:43.481520+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"gene: PTBP2 was added\ngene: PTBP2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PTBP2 were set to 40965981\nPhenotypes for gene: PTBP2 were set to Neurodevelopmental disorder (MONDO:0700092), PTBP2-related\nReview for gene: PTBP2 was set to AMBER\nAdded comment: PMID: 40965981 2 males with developmental delay, ID, autistic features. 1 had some dysmorphic features and tonic-clonic seizures. both probands had a de novo variant in PTBP2 NM_021190.4:c.2T>C (p.Met1?) and NM_021190.4:c.41G>C (p.Arg14Thr), absent from gnomad. Transfection of the variants in transfection in NIH-3T3 cells showed the missense had cytoplasmic retention and colocalization with processing bodies, and that there were 2 alternative downstream start sites Met32 and Met35 that may be used instead. \nSources: Literature","entity_name":"PTBP2","entity_type":"gene"},{"created":"2025-10-10T10:02:59.782734+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"changed review comment from: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1  compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.\r\n\r\nPMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.\r\n\r\nPMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A  variant showed it lead to the out of frame 10bp retention of the intron. \nSources: Literature; to: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1  compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.\r\n\r\nPMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.\r\n\r\nPMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A  variant showed it lead to the out of frame 10bp retention of the intron. Val99Met has 1170 hets and 4 homs in gnomad, as this condition appears to be clinically benign this is not a concern.\r\n\r\nCurrently rated as moderate by ClinGen, the review does not include the most recent paper\r\nSources: Literature","entity_name":"GSTZ1","entity_type":"gene"},{"created":"2025-10-10T10:02:29.963521+11:00","panel_name":"Aminoacidopathy","panel_id":3929,"panel_version":"1.135","user_name":"Lucy Spencer","item_type":"entity","text":"reviewed gene: GSTZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27876694, 38535121, 41009955; Phenotypes: Maleylacetoacetate isomerase deficiency MIM#617596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"GSTZ1","entity_type":"gene"},{"created":"2025-10-10T09:59:27.404268+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Lucy Spencer","item_type":"entity","text":"gene: GSTZ1 was added\ngene: GSTZ1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: GSTZ1 were set to 27876694; 38535121; 41009955\nPhenotypes for gene: GSTZ1 were set to Maleylacetoacetate isomerase deficiency MIM#617596\nReview for gene: GSTZ1 was set to GREEN\nAdded comment: PMID: 27876694 Six newborns with hypersuccinylacetonaemia but normal coagulation testing on initial evaluation. 4 probands homozygous for the recurrent variant c.449C>T (p.Ala150Val), 1  compound heterozygous for c.259C>T (p.Arg87Ter) and c.68-12G>A, and the last only had a single hit c.295G>A (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met showed reduced enzyme activity. Suggested to be a benign biochemical finding as in all patients clinical course has been normal for up to 13 years.\r\n\r\nPMID: 38535121 proband with elevated succinylacetone in DBS on newborn screening. at 2 weeks old this had normalized but traces of succinylacetone were found in urine. Found to have a homozygous variant c.136−2A>G, the mother was heterozygous while the father was homozygous (variant has 2 hets no homs in gnomad). The father was 32yrs old with no medical complaints and a biochemical work up was normal. the proband had microcephaly and short stature but otherwise normal development.\r\n\r\nPMID: 41009955 2 probands with elevated succinylacetone and normal tyrosine levels on NBS. Patient 1 compound heterozygous for c.68-12G>A and c.464_471delinsCTGGG (in frame), patient 2 compound heterozygous for c.68-12G>A and c.295G>A, p.(Val99Met). Patient 1 at 4 yrs of age had normal tyrosine, liver and kidney function tests, and regular development. patient 2 at 2yrs old had good clinical conditions, regular growth and development. RNA seq of the c.68-12G>A  variant showed it lead to the out of frame 10bp retention of the intron. \nSources: Literature","entity_name":"GSTZ1","entity_type":"gene"},{"created":"2025-10-10T09:33:13.291855+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.438","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:33:02.575863+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.437","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGAV as Green List (high evidence)","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:33:02.564116+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.437","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgav has been classified as Green List (High Evidence).","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:32:51.878404+11:00","panel_name":"Fetal anomalies","panel_id":3763,"panel_version":"1.436","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:32:31.356654+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.350","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:31:59.460458+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.349","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGAV as Green List (high evidence)","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:31:59.453444+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.349","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgav has been classified as Green List (High Evidence).","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:31:02.680687+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.348","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:30:30.051547+11:00","panel_name":"Disorders of immune dysregulation","panel_id":229,"panel_version":"1.30","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:30:04.727701+11:00","panel_name":"Disorders of immune dysregulation","panel_id":229,"panel_version":"1.29","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGAV as Green List (high evidence)","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:30:04.720704+11:00","panel_name":"Disorders of immune dysregulation","panel_id":229,"panel_version":"1.29","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgav has been classified as Green List (High Evidence).","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:29:39.718057+11:00","panel_name":"Disorders of immune dysregulation","panel_id":229,"panel_version":"1.28","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:29:23.432270+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3362","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ITGAV were changed from Syndromic disease, MONDO:0002254, ITGAV-related to Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:29:05.787558+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3361","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGAV as Green List (high evidence)","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:29:05.776390+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3361","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgav has been classified as Green List (High Evidence).","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:28:51.479718+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3360","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ITGAV: Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioural abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:28:41.567778+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3360","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ITGAV: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"ITGAV","entity_type":"gene"},{"created":"2025-10-10T09:22:49.510629+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.348","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:22:22.134880+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.347","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:22:06.580824+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.241","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:21:35.328726+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.240","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:21:15.858446+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3360","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:20:51.125310+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3359","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:20:32.214408+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"1.22","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:20:06.538007+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"1.21","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:19:47.499763+11:00","panel_name":"Autism","panel_id":51,"panel_version":"0.222","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UBR5 were changed from Neurodevelopmental disorder MONDO:0700092, UBR5-related to Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-10T09:19:19.023253+11:00","panel_name":"Autism","panel_id":51,"panel_version":"0.221","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and behavioral abnormalities, MIM# 621372; Mode of inheritance: None","entity_name":"UBR5","entity_type":"gene"},{"created":"2025-10-09T19:38:26.550072+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3359","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: CDK9 as Green List (high evidence)","entity_name":"CDK9","entity_type":"gene"},{"created":"2025-10-09T19:38:26.542614+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3359","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: cdk9 has been classified as Green List (High Evidence).","entity_name":"CDK9","entity_type":"gene"},{"created":"2025-10-09T19:37:46.442495+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.3358","user_name":"Bryony Thompson","item_type":"entity","text":"gene: CDK9 was added\ngene: CDK9 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: CDK9 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CDK9 were set to 40954203; 33640901; 30237576; 26633546\nPhenotypes for gene: CDK9 were set to multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome MONDO:0015160; CHARGE-like syndrome with retinal dystrophy\nReview for gene: CDK9 was set to GREEN\nAdded comment: Biallelic variants in at least six unrelated families: \r\n1) proband that displays retinal dystrophy without a CHARGE-like malformation syndrome (c.862G>A/p.A288T + c.961C>T/p.P321S). \r\n2) A boy with a phenotype resembling CHARGE syndrome (multiple anomalies involving the eyes, ears, cleft lip, and palate, and intellectual disability) with retinal dystrophy (p.A288T/p.R303C), \r\n3-7) 4 consanguineous families homozygous for p.R225C, including a set of cousins.\r\nCDK9 variants demonstrated decreased kinase activity. One of the studies suggested the extent the kinase activity is reduced may account for the absence/presence of the CHARGE-like phenotype with retinal dystrophy \nSources: Literature","entity_name":"CDK9","entity_type":"gene"}]}