Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000999614 | SCV001156318 | uncertain significance | Brugada syndrome; Sudden unexplained death | 2018-03-07 | criteria provided, single submitter | research | This variant has not been previously reported and is present in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified the KCNJ8 p.Arg274Cys variant in a patient who suffered a sudden unexplained death, whom has a family history of Brugada Syndrome and a second variant SCN5A p.Gly1642Glu. Whilst this variant was found to segregate with disease in our family (3 meiosis), so did the SCN5A p.Gly1642Glu. |
Invitae | RCV001858902 | SCV002223413 | uncertain significance | Brugada syndrome | 2021-02-16 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with KCNJ8-related conditions. ClinVar contains an entry for this variant (Variation ID: 810767). This variant is present in population databases (rs781083385, ExAC 0.006%). This sequence change replaces arginine with cysteine at codon 274 of the KCNJ8 protein (p.Arg274Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. |
Ambry Genetics | RCV002427451 | SCV002680149 | uncertain significance | Cardiovascular phenotype | 2022-09-05 | criteria provided, single submitter | clinical testing | The p.R274C variant (also known as c.820C>T), located in coding exon 2 of the KCNJ8 gene, results from a C to T substitution at nucleotide position 820. The arginine at codon 274 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |