Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002533230 | SCV000760678 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2017-11-02 | 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 present in population databases (rs190787113, ExAC 0.001%). This sequence change replaces arginine with glutamine at codon 694 of the RYR2 protein (p.Arg694Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. |
Color Diagnostics, |
RCV001175906 | SCV001339717 | uncertain significance | Cardiomyopathy | 2019-12-11 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 694 of the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/249290 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |