ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.9454C>T (p.Arg3152Cys)

gnomAD frequency: 0.00001  dbSNP: rs181105904
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002552470 SCV001200424 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2023-07-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3152 of the RYR2 protein (p.Arg3152Cys). This variant is present in population databases (rs181105904, 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: 836013). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR2 protein function. 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.
Color Diagnostics, LLC DBA Color Health RCV001187349 SCV001354123 uncertain significance Cardiomyopathy 2023-04-11 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/238954 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.
Ambry Genetics RCV002551373 SCV003600152 uncertain significance Inborn genetic diseases 2022-06-03 criteria provided, single submitter clinical testing The c.9454C>T (p.R3152C) alteration is located in exon 67 (coding exon 67) of the RYR2 gene. This alteration results from a C to T substitution at nucleotide position 9454, causing the arginine (R) at amino acid position 3152 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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