ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.9569G>A (p.Arg3190Gln) (rs369276868)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000778056 SCV000914171 uncertain significance Cardiomyopathy 2018-08-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic domain of the RYR2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/263048 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
GeneDx RCV000182883 SCV000235271 uncertain significance not provided 2015-02-19 criteria provided, single submitter clinical testing This missense change is denoted Arg3190Gln (aka R3190Q) at the protein level and c.9569 G>A at the cDNA level. The Arg3190Gln variant in the RYR2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Arg3190Gln results in a non-conservative amino acid substitution of a positively charged Arginine residue with a neutral, polar Glutamine residue at a position that is class conserved in mammals. Arg3190Gln was not observed in up to 600 control alleles from individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign polymorphism in these populations. Nevertheless, Arg3190Gln is located in a region of the protein without reported mutations in surrounding codons, indicating this region may be tolerant of change. In summary, we cannot determine if Arg3190Gln in RYR2 is a disease-causing mutation or a rare benign variant, and further studies are needed to clarify the biological relevance of this variant. The variant is found in ARVC panel(s).

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