ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.525dup (p.Val176fs) (rs558037268)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000411870 SCV000694468 pathogenic Wilson disease 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.525dupA (p.Val176Serfs) 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. One in silico tool predicts a damaging outcome for this variant. This variant was found in 3/120674 control chromosomes at a frequency of 0.0000249, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). The variant has been reported in the literature in numerous affected individuals, mainly of Chinese ancestry. Taken together, this variant is classified as pathogenic.
Invitae RCV000411870 SCV000961685 pathogenic Wilson disease 2019-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val176Serfs*28) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs758115611, ExAC 0.03%). This variant has been observed to be homozygous or in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 27022412, 21034864, 26483271, 29321352). This variant is also known as c.525_526insA in the literature. ClinVar contains an entry for this variant (Variation ID: 370306). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000411870 SCV000485576 pathogenic Wilson disease 2016-09-09 no assertion criteria provided clinical testing

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