ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12638A>G (p.Glu4213Gly)

gnomAD frequency: 0.00001  dbSNP: rs1178157004
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002541904 SCV001488888 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-05-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002447282 SCV002677606 uncertain significance Cardiovascular phenotype 2019-05-15 criteria provided, single submitter clinical testing The p.E4213G variant (also known as c.12638A>G), located in coding exon 90 of the RYR2 gene, results from an A to G substitution at nucleotide position 12638. The glutamic acid at codon 4213 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, glycine 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.
Fulgent Genetics, Fulgent Genetics RCV002493581 SCV002784477 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-08-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004991 SCV004824723 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 4213 of 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 2/280072 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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