ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.7354G>A (p.Val2452Met)

gnomAD frequency: 0.00003  dbSNP: rs377136047
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002522785 SCV000541694 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2025-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620494 SCV000736953 uncertain significance Cardiovascular phenotype 2023-02-13 criteria provided, single submitter clinical testing The p.V2452M variant (also known as c.7354G>A), located in coding exon 49 of the RYR2 gene, results from a G to A substitution at nucleotide position 7354. The valine at codon 2452 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, methionine is the reference amino acid in other 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.
Color Diagnostics, LLC DBA Color Health RCV001184262 SCV001350209 uncertain significance Cardiomyopathy 2023-05-08 criteria provided, single submitter clinical testing This variant is located in 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 7/271920 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.
Fulgent Genetics, Fulgent Genetics RCV002488999 SCV002780332 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-11-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000622 SCV004822068 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-06-09 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 2452 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 RYR2-related disorders in the literature. This variant has been identified in 7/271920 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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