Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000004070 | SCV000220735 | likely pathogenic | Wilson disease | 2014-09-24 | criteria provided, single submitter | literature only | |
Invitae | RCV000004070 | SCV001389674 | pathogenic | Wilson disease | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 691 of the ATP7B protein (p.Gly691Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Wilson disease (PMID: 9671269, 17718866, 23389864). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3866). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000004070 | SCV001977355 | likely pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004070 | SCV002819939 | pathogenic | Wilson disease | 2022-12-05 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.2071G>A (p.Gly691Arg) results in a non-conservative amino acid change located in the TM2 domain (Loudianos_1998) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249376 control chromosomes (gnomAD and publication data). c.2071G>A has been reported in the literature in multiple individuals affected with Wilson Disease, including homozygotes (Loudianos_1998, Barada_2007, Couchonnal_2021). 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000004070 | SCV004216454 | pathogenic | Wilson disease | 2023-03-16 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004070 | SCV000024236 | pathogenic | Wilson disease | 2007-09-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000004070 | SCV002087854 | pathogenic | Wilson disease | 2021-02-17 | no assertion criteria provided | clinical testing |