Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001179056 | SCV001343637 | uncertain significance | Cardiomyopathy | 2019-04-29 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 1091 of the RYR2 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact 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 2/249062 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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 | RCV002444650 | SCV002612548 | uncertain significance | Cardiovascular phenotype | 2019-05-31 | criteria provided, single submitter | clinical testing | The p.E1091K variant (also known as c.3271G>A), located in coding exon 28 of the RYR2 gene, results from a G to A substitution at nucleotide position 3271. The glutamic acid at codon 1091 is replaced by lysine, 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. |
| Labcorp Genetics |
RCV000157453 | SCV004507707 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1091 of the RYR2 protein (p.Glu1091Lys). This variant is present in population databases (rs730880191, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of RYR2-related conditions (PMID: 35877578). ClinVar contains an entry for this variant (Variation ID: 180493). Invitae Evidence 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 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. |
| Human Genetics Bochum, |
RCV003886381 | SCV004704507 | uncertain significance | Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PP3_STR, PM2_SUP |
| Blueprint Genetics | RCV000157453 | SCV000207197 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2014-05-28 | no assertion criteria provided | clinical testing |