ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.1428C>G (p.Tyr476Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV002465388 SCV004809058 pathogenic Creatine transporter deficiency 2024-02-22 reviewed by expert panel curation The NM_005629.4: c.1428C>G (p.Tyr476Ter) variant in SLC6A8 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10/13, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported a male with intellectual disability, autistic features, seizures and absent creatine peak on brain MRS (PMID: 29435807) (PP4). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 1802549). In summary, this variant meets the criteria to be classified as pathogenic for creatine transporter deficiency. SLC6A8-specific criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PVS1, PP4, PM2_Supporting. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on February 22, 2024).
Laboratory of Medical Genetics, University of Torino RCV002465388 SCV002760055 likely pathogenic Creatine transporter deficiency 2022-11-29 criteria provided, single submitter research

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