ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6233C>T (p.Pro2078Leu)

gnomAD frequency: 0.00001  dbSNP: rs1158268722
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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 RCV001187470 SCV001354288 uncertain significance Cardiomyopathy 2020-12-23 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 not been identified 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 RCV002365874 SCV002658245 uncertain significance Cardiovascular phenotype 2022-06-06 criteria provided, single submitter clinical testing The p.P2078L variant (also known as c.6233C>T), located in coding exon 41 of the RYR2 gene, results from a C to T substitution at nucleotide position 6233. The proline at codon 2078 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491557 SCV002777097 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2022-02-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008701 SCV004820845 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-04-25 criteria provided, single submitter clinical testing This variant is located in the RYR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 not been identified 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.
GeneDx RCV004720781 SCV005326792 uncertain significance not provided 2024-02-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); 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)

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