ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.524_525del (p.Lys175fs) (rs558037268)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169375 SCV000220755 likely pathogenic Wilson disease 2014-09-30 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000169375 SCV000694467 likely pathogenic Wilson disease 2017-02-03 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.524_525delAA (p.Lys175Serfs) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B 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 (e.g. c.525dupA (p.Val176fs); c.845delT (p.Leu282fs); c.1145_1151delCCCAACT(p.Ser382fs); etc.). This variant is absent in 120674 control chromosomes from ExAC and has been reported in one WD patient who carried a known pathogenic variant p.H1069Q in compound heterozygous state in the literature. In addition, one clinical diagnostic laboratory/reputable database has classified this variant as likely pathogenic. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000169375 SCV000752247 pathogenic Wilson disease 2019-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys175Serfs*28) 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 reported in an individual affected with Wilson disease (PMID: 17680703). ClinVar contains an entry for this variant (Variation ID: 188995). 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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