ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.340C>G (p.Leu114Val)

gnomAD frequency: 0.00001  dbSNP: rs759271857
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002562983 SCV001390364 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2019-07-05 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 C25"). This variant has not been reported in the literature in individuals with RYR2-related conditions. This variant is present in population databases (rs759271857, ExAC 0.04%). This sequence change replaces leucine with valine at codon 114 of the RYR2 protein (p.Leu114Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine.
Ambry Genetics RCV002451493 SCV002612742 uncertain significance Cardiovascular phenotype 2022-09-07 criteria provided, single submitter clinical testing The p.L114V variant (also known as c.340C>G), located in coding exon 6 of the RYR2 gene, results from a C to G substitution at nucleotide position 340. The leucine at codon 114 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a catecholaminergic polymorphic ventricular tachycardia (CPVT) genetic testing cohort; however, clinical details were limited (Kapplinger JD et al. Circ Genom Precis Med, 2018 02;11:e001424). 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.

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