ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12837G>A (p.Met4279Ile)

gnomAD frequency: 0.00004  dbSNP: rs750117613
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208489 SCV000264191 uncertain significance Primary dilated cardiomyopathy 2015-03-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002515553 SCV000760681 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-10-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194102 SCV001363383 uncertain significance not specified 2019-11-29 criteria provided, single submitter clinical testing Variant summary: RYR2 c.12837G>A (p.Met4279Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 248598 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.12837G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002381717 SCV002691137 uncertain significance Cardiovascular phenotype 2021-10-21 criteria provided, single submitter clinical testing The p.M4279I variant (also known as c.12837G>A), located in coding exon 90 of the RYR2 gene, results from a G to A substitution at nucleotide position 12837. The methionine at codon 4279 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002494544 SCV002796990 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-10-11 criteria provided, single submitter clinical testing

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