ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2668G>A (p.Val890Met) (rs786204718)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169535 SCV000221015 likely pathogenic Wilson disease 2015-01-08 criteria provided, single submitter literature only
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514615 SCV000609693 pathogenic not provided 2017-08-23 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000169535 SCV000845443 uncertain significance Wilson disease 2018-08-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000169535 SCV000916634 pathogenic Wilson disease 2018-11-02 criteria provided, single submitter clinical testing Variant summary: ATP7B c.2668G>A (p.Val890Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 277226 control chromosomes. c.2668G>A has been reported in the literature in multiple individuals affected with Wilson Disease. These 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000169535 SCV001228417 likely pathogenic Wilson disease 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 890 of the ATP7B protein (p.Val890Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with Wilson disease (PMID: 14986826, 29637721, 22308153, 29979436, 22484412, 11216666, 27022412, 22677543). ClinVar contains an entry for this variant (Variation ID: 189121). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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