Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001225347 | SCV001397625 | uncertain significance | Brugada syndrome | 2019-11-10 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNJ8-related conditions. This variant is present in population databases (rs752063865, ExAC 0.003%). This sequence change replaces lysine with arginine at codon 382 of the KCNJ8 protein (p.Lys382Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |
| Ambry Genetics | RCV003353223 | SCV004057096 | uncertain significance | Cardiovascular phenotype | 2023-06-22 | criteria provided, single submitter | clinical testing | The p.K382R variant (also known as c.1145A>G), located in coding exon 2 of the KCNJ8 gene, results from an A to G substitution at nucleotide position 1145. The lysine at codon 382 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |