ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13175A>G (p.Lys4392Arg) (rs753733164)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698208 SCV000826858 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2019-07-24 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 4392 of the RYR2 protein (p.Lys4392Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs753733164, ExAC 0.01%). This variant has been observed in individuals affected with catecholaminergic polymorphic ventricular tachycardia (PMID: 25092222, 23595086). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001101825 SCV001258466 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001101826 SCV001258467 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color RCV001181816 SCV001347050 uncertain significance Cardiomyopathy 2020-01-15 criteria provided, single submitter clinical testing

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