Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692088 | SCV000819895 | uncertain significance | Brugada syndrome | 2018-02-01 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with KCNJ8-related disease. ClinVar contains an entry for this variant (Variation ID: 180388). This sequence change replaces arginine with serine at codon 394 of the KCNJ8 protein (p.Arg394Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV002336343 | SCV002635860 | uncertain significance | Cardiovascular phenotype | 2022-05-06 | criteria provided, single submitter | clinical testing | The p.R394S variant (also known as c.1182G>C), located in coding exon 2 of the KCNJ8 gene, results from a G to C substitution at nucleotide position 1182. The arginine at codon 394 is replaced by serine, an amino acid with dissimilar 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. |
Blueprint Genetics | RCV001842498 | SCV000207005 | uncertain significance | Cardiac arrhythmia | 2014-11-13 | no assertion criteria provided | clinical testing |