ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2227del (p.Tyr743fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001070456 SCV001235688 pathogenic Wilson disease 2019-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr743Ilefs*19) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Wilson disease (PMID: 23551039). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001070456 SCV001431917 likely pathogenic Wilson disease 2020-08-24 criteria provided, single submitter clinical testing Variant summary: ATP7B c.2227delT (p.Tyr743IlefsX19) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249582 control chromosomes (gnomAD). c.2227delT has been reported in the literature in one individual affected with Wilson Disease (Aggarwal_2013). The data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV001509444 SCV001716170 pathogenic not provided 2021-03-25 criteria provided, single submitter clinical testing PVS1, PM2, PP4

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