Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523159 | SCV000618680 | uncertain significance | not provided | 2021-03-30 | criteria provided, single submitter | clinical testing | Reported as an incidental finding in a cohort of individuals referred for whole exome sequencing; however, specific clinical information about the individual(s) harboring this variant was not provided (Landstrom et al., 2017); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#450136; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009); This variant is associated with the following publications: (PMID: 28404607) |
Color Diagnostics, |
RCV001183827 | SCV001349669 | uncertain significance | Cardiomyopathy | 2023-03-13 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 3706 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has been identified in 2/217498 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. |
Invitae | RCV002525153 | SCV001415150 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-01-11 | criteria provided, single submitter | clinical testing |