Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182684 | SCV000235063 | uncertain significance | not provided | 2018-06-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the RYR2 gene. The E521K variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 18/17234 (0.1%) alleles from individuals of East Asian ancestry in large population cohorts (Lek et al., 2016). Additionally, the E521K variant is not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009). Nonetheless, the E521K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Color Diagnostics, |
RCV001189917 | SCV001357302 | likely benign | Cardiomyopathy | 2019-06-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002516869 | SCV001630114 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-08-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002399658 | SCV002704969 | uncertain significance | Cardiovascular phenotype | 2018-11-20 | criteria provided, single submitter | clinical testing | The p.E521K variant (also known as c.1561G>A), located in coding exon 16 of the RYR2 gene, results from a G to A substitution at nucleotide position 1561. The glutamic acid at codon 521 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |