Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001917726 | SCV002177500 | uncertain significance | Brugada syndrome 4 | 2021-05-30 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs760811952, ExAC 0.03%) but has not been reported in the literature in individuals with a CACNB2-related disease. This sequence change replaces arginine with glycine at codon 509 of the CACNB2 protein (p.Arg509Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Ambry Genetics | RCV002388796 | SCV002709646 | uncertain significance | Cardiovascular phenotype | 2021-11-09 | criteria provided, single submitter | clinical testing | The p.R509G variant (also known as c.1525C>G), located in coding exon 13 of the CACNB2 gene, results from a C to G substitution at nucleotide position 1525. The arginine at codon 509 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |