ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.970A>T (p.Lys324Ter) (rs911589273)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780927 SCV000918587 likely pathogenic Wilson disease 2018-02-21 criteria provided, single submitter clinical testing Variant summary: ATP7B c.970A>T (p.Lys324X) 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 (eg. c.1531C>T (p.Gln511X), c.2149C>T (p.Gln717X), and c.2336G>A (p.Trp779X)). The variant was absent from 245940 control chromosomes of gnomAD dataset. To our knowledge, no occurrence of c.970A>T in individuals affected with Wilson Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000780927 SCV001417326 pathogenic Wilson disease 2019-10-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys324*) 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 not been reported in the literature in individuals with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 633065). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.

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