Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002553108 | SCV001207839 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-08-11 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 841771). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 3018 of the RYR2 protein (p.Arg3018Gly). |
Ambry Genetics | RCV002372781 | SCV002687201 | uncertain significance | Cardiovascular phenotype | 2023-05-22 | criteria provided, single submitter | clinical testing | The p.R3018G variant (also known as c.9052A>G), located in coding exon 63 of the RYR2 gene, results from an A to G substitution at nucleotide position 9052. The arginine at codon 3018 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly 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. |