Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000695087 | SCV000823566 | uncertain significance | Brugada syndrome | 2020-03-07 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with KCNJ8-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 240 of the KCNJ8 protein (p.Val240Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. |
| Ambry Genetics | RCV002369882 | SCV002673399 | uncertain significance | Cardiovascular phenotype | 2022-09-24 | criteria provided, single submitter | clinical testing | The p.V240A variant (also known as c.719T>C), located in coding exon 2 of the KCNJ8 gene, results from a T to C substitution at nucleotide position 719. The valine at codon 240 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |