ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.7874G>C (p.Gly2625Ala)

dbSNP: rs1331814541
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002543067 SCV001487654 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 2625 of the RYR2 protein (p.Gly2625Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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.
Color Diagnostics, LLC DBA Color Health RCV001525106 SCV001735125 uncertain significance Cardiomyopathy 2023-04-28 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/249220 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.
Ambry Genetics RCV002411951 SCV002676830 uncertain significance Cardiovascular phenotype 2022-09-30 criteria provided, single submitter clinical testing The p.G2625A variant (also known as c.7874G>C), located in coding exon 52 of the RYR2 gene, results from a G to C substitution at nucleotide position 7874. The glycine at codon 2625 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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.
All of Us Research Program, National Institutes of Health RCV004004979 SCV004822707 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-07-20 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/249220 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.

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