ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3083_3085delinsG (p.Lys1028fs) (rs1331370011)

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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 RCV000780937 SCV000918606 pathogenic Wilson disease 2018-12-03 criteria provided, single submitter clinical testing Variant summary: ATP7B c.3083_3085delinsG (p.Lys1028SerfsX40) 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.3402delC, p.Ala1135fsX13; c.3955C>T, p.Arg1319X; c.4051C>T, p.Gln1351X). The variant was absent in 244720 control chromosomes (gnomAD). The variant, c.3083_3085delinsG, has been reported in the literature in individuals affected with Wilson Disease (Figus_1995, Bost_2012, Collet_2018, Waldenstrom_1996). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 pathogenic.
Invitae RCV000780937 SCV001415722 pathogenic Wilson disease 2019-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1028Serfs*40) 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 the homozygous state in an individual affected with Wilson disease (PMID: 8533760). This variant is also known as 3085delAGA>G in the literature. 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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