ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5593G>A (p.Glu1865Lys)

gnomAD frequency: 0.00004  dbSNP: rs553819263
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000774210 SCV000907911 uncertain significance Cardiomyopathy 2023-11-28 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1865 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 10/248348 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.
Invitae RCV002536678 SCV002361400 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-08-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343625 SCV002647447 uncertain significance Cardiovascular phenotype 2022-08-25 criteria provided, single submitter clinical testing The p.E1865K variant (also known as c.5593G>A), located in coding exon 37 of the RYR2 gene, results from a G to A substitution at nucleotide position 5593. The glutamic acid at codon 1865 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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