ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.295A>C (p.Lys99Gln)

gnomAD frequency: 0.00003  dbSNP: rs1172697175
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002534875 SCV000956133 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 99 of the RYR2 protein (p.Lys99Gln). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 658783). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002487793 SCV002785500 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-10-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV003353055 SCV004054067 uncertain significance Cardiovascular phenotype 2023-06-26 criteria provided, single submitter clinical testing The p.K99Q variant (also known as c.295A>C) is located in coding exon 5 of the RYR2 gene. The lysine at codon 99 is replaced by glutamine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 5. This amino acid position is highly 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.

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