Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673544 | SCV000798757 | likely pathogenic | Wilson disease | 2018-03-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000673544 | SCV000935825 | pathogenic | Wilson disease | 2023-12-17 | 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 1000 of the ATP7B protein (p.Gly1000Arg). This variant is present in population databases (rs751078884, gnomAD 0.007%). This missense change has been observed in individual(s) with Wilson disease (PMID: 31059521). ClinVar contains an entry for this variant (Variation ID: 557405). 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%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 20333758). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000673544 | SCV001977143 | likely pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Arcensus | RCV000673544 | SCV002564616 | likely pathogenic | Wilson disease | 2013-02-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000673544 | SCV002780465 | likely pathogenic | Wilson disease | 2021-10-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003319396 | SCV004023789 | pathogenic | not provided | 2023-08-03 | criteria provided, single submitter | clinical testing | Published functional studies found this variant is unable to rescue growth of a yeast strain deficient for ccc2 (the ATP7B otholog in yeast) (Luoma LM et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16088907, 30120852, 20333758, 30275481, 22692182, 31708252, 23486543) |