Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002563067 | SCV001397279 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 3223 of the RYR2 protein (p.Glu3223Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs377626309, ExAC 0.007%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). 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. |
| Ambry Genetics | RCV002379854 | SCV002693893 | uncertain significance | Cardiovascular phenotype | 2022-08-22 | criteria provided, single submitter | clinical testing | The p.E3223D variant (also known as c.9669G>C), located in coding exon 68 of the RYR2 gene, results from a G to C substitution at nucleotide position 9669. The glutamic acid at codon 3223 is replaced by aspartic acid, an amino acid with highly 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. |