Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002406340 | SCV002710176 | uncertain significance | Cardiovascular phenotype | 2024-01-31 | criteria provided, single submitter | clinical testing | The p.R352Q variant (also known as c.1055G>A), located in coding exon 2 of the KCNJ8 gene, results from a G to A substitution at nucleotide position 1055. The arginine at codon 352 is replaced by glutamine, an amino acid with highly similar properties. In one study, this variant was identified in an exome cohort, and was not associated with J-point elevation (Ghouse J et al. Genet. Med., 2017 05;19:521-528). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003108083 | SCV003780676 | uncertain significance | Brugada syndrome | 2023-09-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with KCNJ8-related conditions. This variant is present in population databases (rs747622709, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 352 of the KCNJ8 protein (p.Arg352Gln). ClinVar contains an entry for this variant (Variation ID: 1778395). 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 KCNJ8 protein function. |