ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.7459C>A (p.Leu2487Ile)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001097574 SCV001253864 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001097575 SCV001253865 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Color RCV001183411 SCV001349130 uncertain significance Cardiomyopathy 2019-10-18 criteria provided, single submitter clinical testing
Invitae RCV001233605 SCV001406207 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 2487 of the RYR2 protein (p.Leu2487Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs748581317, ExAC 0.01%). This variant has not been reported in the literature in individuals with RYR2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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