Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000004059 | SCV000192324 | pathogenic | Wilson disease | 2018-03-15 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000004059 | SCV000486748 | pathogenic | Wilson disease | 2016-08-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000004059 | SCV001977336 | pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000004059 | SCV002247011 | pathogenic | Wilson disease | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 765 of the ATP7B protein (p.Asp765Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Wilson disease (PMID: 15024742, 20517649). This variant is also known as Asp766Asn. ClinVar contains an entry for this variant (Variation ID: 3855). 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: 9837819, 10942420). This variant disrupts the p.Asp765 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23843956, 30384382). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004059 | SCV002511694 | pathogenic | Wilson disease | 2022-04-01 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.2293G>A (p.Asp765Asn) 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 was absent in 249564 control chromosomes. c.2293G>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. Four 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. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000004059 | SCV004216340 | pathogenic | Wilson disease | 2023-09-08 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004059 | SCV000024225 | pathogenic | Wilson disease | 1995-12-01 | no assertion criteria provided | literature only |