ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2002A>G (p.Met668Val)

dbSNP: rs587783301
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000145257 SCV000192317 likely pathogenic Wilson disease 2018-03-29 criteria provided, single submitter clinical testing
GeneDx RCV000427356 SCV000535376 likely pathogenic not provided 2017-01-12 criteria provided, single submitter clinical testing The M668V variant in the ATP7B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M668V variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M668V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The M668V variant is a strong candidate for a pathogenic variant; however, the possibility it may be a rare benign variant cannot be completely excluded.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265624 SCV002548276 uncertain significance not specified 2022-05-21 criteria provided, single submitter clinical testing Variant summary: ATP7B c.2002A>G (p.Met668Val) 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 4e-06 in 249224 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2002A>G in individuals affected with Wilson Disease and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Likely pathogenic, n=2; VUS, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Counsyl RCV000145257 SCV000800505 uncertain significance Wilson disease 2017-03-15 no assertion criteria provided clinical testing

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