ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.10043T>G (p.Met3348Arg)

dbSNP: rs794728767
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182782 SCV000235168 uncertain significance not provided 2014-04-04 criteria provided, single submitter clinical testing p.Met3348Arg (ATG>AGG): c.10043 T>G in exon 69 of the RYR2 gene (NM_001035.2). The M3348R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The M3348R variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M3348R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported in association with disease, suggesting this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s).
Ambry Genetics RCV002399662 SCV002709358 uncertain significance Cardiovascular phenotype 2019-09-18 criteria provided, single submitter clinical testing The p.M3348R variant (also known as c.10043T>G), located in coding exon 69 of the RYR2 gene, results from a T to G substitution at nucleotide position 10043. The methionine at codon 3348 is replaced by arginine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV000182782 SCV005411595 uncertain significance not provided 2024-03-27 criteria provided, single submitter clinical testing PM2

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