Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003103912 | SCV001223555 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-08-18 | 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: "Benign"; Align-GVGD: "Class C65"). This sequence change replaces arginine with cysteine at codon 1358 of the RYR2 protein (p.Arg1358Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs771593145, ExAC 0.006%). This variant has not been reported in the literature in individuals with RYR2-related conditions. |
Color Diagnostics, |
RCV001192304 | SCV001360334 | uncertain significance | Cardiomyopathy | 2023-06-01 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 1358 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/248494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |