ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13252A>G (p.Lys4418Glu)

gnomAD frequency: 0.00001  dbSNP: rs1029442866
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001804586 SCV002053345 uncertain significance Cardiomyopathy 2021-03-03 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 4418 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 cardiovascular disorders in the literature. This variant has been identified in 2/196500 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002541414 SCV002214641 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2025-01-27 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004804242 SCV005428131 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 4418 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 cardiovascular disorders in the literature. This variant has been identified in 2/196500 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.
Ambry Genetics RCV004988758 SCV005496968 uncertain significance Cardiovascular phenotype 2024-08-11 criteria provided, single submitter clinical testing The p.K4418E variant (also known as c.13252A>G), located in coding exon 90 of the RYR2 gene, results from an A to G substitution at nucleotide position 13252. The lysine at codon 4418 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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