Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001239073 | SCV001411919 | uncertain significance | Andersen Tawil syndrome; Short QT syndrome type 3 | 2023-09-09 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt KCNJ2 protein function. ClinVar contains an entry for this variant (Variation ID: 964778). This variant has not been reported in the literature in individuals affected with KCNJ2-related conditions. This variant is present in population databases (rs150326473, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 171 of the KCNJ2 protein (p.Ile171Val). |
Ambry Genetics | RCV002348811 | SCV002646505 | benign | Cardiovascular phenotype | 2024-03-22 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Gene |
RCV003313196 | SCV004012698 | uncertain significance | not provided | 2023-01-09 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |