Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001183754 | SCV001349573 | likely benign | Cardiomyopathy | 2019-03-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002559845 | SCV001394022 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-09-16 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 3546 of the RYR2 protein (p.Lys3546Arg). 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 affected with RYR2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002411692 | SCV002711139 | uncertain significance | Cardiovascular phenotype | 2020-09-14 | criteria provided, single submitter | clinical testing | The p.K3546R variant (also known as c.10637A>G), located in coding exon 74 of the RYR2 gene, results from an A to G substitution at nucleotide position 10637. The lysine at codon 3546 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and 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. |