ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2072G>T (p.Gly691Val) (rs1555291801)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671031 SCV000795969 likely pathogenic Wilson disease 2017-11-26 criteria provided, single submitter clinical testing
Invitae RCV000671031 SCV000825523 pathogenic Wilson disease 2018-06-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 691 of the ATP7B protein (p.Gly691Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous or in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 25497208). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Gly691Arg) has been determined to be likely pathogenic (PMID: 17718866, 23389864, 9671269). This suggests that the glycine residue is critical for ATP7B protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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