ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.3244G>A (p.Gly1082Arg)

gnomAD frequency: 0.00001  dbSNP: rs774797663
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192032 SCV001359976 uncertain significance Cardiomyopathy 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 1082 of the RYR2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/248946 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 RCV002560137 SCV001544777 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-05-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1082 of the RYR2 protein (p.Gly1082Arg). This variant is present in population databases (rs774797663, gnomAD 0.007%). 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: 928258). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR2 protein function with a negative predictive value of 95%. 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 RCV002484056 SCV002776871 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-10-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003293973 SCV003999093 uncertain significance Cardiovascular phenotype 2023-06-04 criteria provided, single submitter clinical testing The p.G1082R variant (also known as c.3244G>A), located in coding exon 28 of the RYR2 gene, results from a G to A substitution at nucleotide position 3244. The glycine at codon 1082 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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.
All of Us Research Program, National Institutes of Health RCV004010564 SCV004821370 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 1082 of the RYR2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/248946 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.

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