Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781827 | SCV000920175 | uncertain significance | not specified | 2018-12-26 | criteria provided, single submitter | clinical testing | Variant summary: RYR2 c.749G>T (p.Gly250Val) results in a non-conservative amino acid change located in the MIR motif (IPR016093) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245984 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.749G>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002388410 | SCV002670487 | uncertain significance | Cardiovascular phenotype | 2022-07-05 | criteria provided, single submitter | clinical testing | The p.G250V variant (also known as c.749G>T), located in coding exon 10 of the RYR2 gene, results from a G to T substitution at nucleotide position 749. The glycine at codon 250 is replaced by valine, 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. |
| Invitae | RCV003638712 | SCV004424319 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-11-03 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 633402). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 250 of the RYR2 protein (p.Gly250Val). |