ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8407C>T (p.Arg2803Trp)

gnomAD frequency: 0.00002  dbSNP: rs754674622
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003104051 SCV001542195 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2025-01-26 criteria provided, single submitter clinical testing
GeneDx RCV001776213 SCV002012569 uncertain significance not provided 2024-12-10 criteria provided, single submitter clinical testing Identified in a patient with ischemic cardiomyopathy who also harbored a variant in the JUP gene (Cuesta-Llavona, E et al. (2022) Cardiogenetics(12):198205. https://doi.org/10.3390/cardiogenetics12020018); Not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur. (PMID: 19926015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19926015)
Ambry Genetics RCV002412092 SCV002675795 uncertain significance Cardiovascular phenotype 2023-09-12 criteria provided, single submitter clinical testing The p.R2803W variant (also known as c.8407C>T), located in coding exon 56 of the RYR2 gene, results from a C to T substitution at nucleotide position 8407. The arginine at codon 2803 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is 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 RCV004005217 SCV004819730 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 2803 of 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 been reported in an individual affected with cardiac ischemia who underwent heart transplantation (doi:10.3390/cardiogenetics12020018). This variant has been identified in 5/160220 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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