ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13957G>A (p.Val4653Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002389084 SCV002700117 uncertain significance Cardiovascular phenotype 2022-04-05 criteria provided, single submitter clinical testing The p.V4653I variant (also known as c.13957G>A) is located in coding exon 97 of the RYR2 gene, results from a G to A substitution as nucleotide position 13957. This variant impacts the first base pair of coding exon 97. The valine at codon 4653 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV004007312 SCV004824627 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-05-04 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 RYR2-related disorders in the literature. This variant has been identified in 4/242204 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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