Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656548 | SCV001388639 | uncertain significance | not provided | 2020-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 1922 of the SCN5A protein (p.Lys1922Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV002356923 | SCV002648600 | uncertain significance | Cardiovascular phenotype | 2021-04-15 | criteria provided, single submitter | clinical testing | The p.K1922R variant (also known as c.5765A>G), located in coding exon 27 of the SCN5A gene, results from an A to G substitution at nucleotide position 5765. The lysine at codon 1922 is replaced by arginine, an amino acid with highly similar properties, and is located in the cytoplasmic C-terminal domain. This amino acid position is well conserved in available vertebrate species; however, arginine is the reference amino acid in other 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. |