Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002534586 | SCV000935291 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2018-10-22 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 4177 of the RYR2 protein (p.Val4177Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |
Ambry Genetics | RCV002534587 | SCV003549982 | uncertain significance | Inborn genetic diseases | 2021-01-13 | criteria provided, single submitter | clinical testing | The c.12530T>A (p.V4177D) alteration is located in coding exon 90 of the RYR2 gene. This alteration results from a T to A substitution at nucleotide position 12530, causing the valine (V) at amino acid position 4177 to be replaced by an aspartic acid (D). Based on data from the Genome Aggregation Database (gnomAD), the RYR2 c.12530T>A alteration was not observed, with coverage at this position. The p.V4177 amino acid is conserved in available vertebrate species. The p.V4177D alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |