ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4040T>G (p.Met1347Arg)

gnomAD frequency: 0.00001  dbSNP: rs193922625
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001841542 SCV000053090 likely pathogenic Cardiac arrhythmia 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001189912 SCV001357297 uncertain significance Cardiomyopathy 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces methionine with arginine at codon 1347 of the RYR2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223835 SCV000280451 uncertain significance not specified 2015-10-05 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. RYR2 Met1347Arg (c.4040T>G), heterozygous, missense . A nonpolar neutral Methionine is replaced with a polar, positive Arginine at nucleotide 1347 of the RYR2 gene, net charge is affected. Other variants in this gene have been associated CPVT and ARVC. The lab reports this variant is novel. In silico analysis predicts the amino acid change to be tolerated and benign (SIFT, Poly Phen).

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