Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001955706 | SCV002220093 | uncertain significance | Long QT syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 197 of the KCNJ5 protein (p.Ala197Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with KCNJ5-related conditions. 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 KCNJ5 protein function. 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. |
Ambry Genetics | RCV003303471 | SCV003992286 | uncertain significance | Cardiovascular phenotype | 2023-03-27 | criteria provided, single submitter | clinical testing | The p.A197V variant (also known as c.590C>T), located in coding exon 1 of the KCNJ5 gene, results from a C to T substitution at nucleotide position 590. The alanine at codon 197 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003490964 | SCV004241198 | uncertain significance | not specified | 2023-12-17 | criteria provided, single submitter | clinical testing |