ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.1423A>C (p.Lys475Gln)

gnomAD frequency: 0.00001  dbSNP: rs765389300
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002531479 SCV000822325 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-08-31 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477572 SCV000896295 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-07-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001187697 SCV001354567 uncertain significance Cardiomyopathy 2023-10-05 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamine at codon 475 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 7/248680 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 RCV003362898 SCV004054103 uncertain significance Cardiovascular phenotype 2023-09-07 criteria provided, single submitter clinical testing The p.K475Q variant (also known as c.1423A>C), located in coding exon 15 of the RYR2 gene, results from an A to C substitution at nucleotide position 1423. The lysine at codon 475 is replaced by glutamine, an amino acid with similar properties. This amino acid position is 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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