Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001065256 | SCV001230209 | uncertain significance | Brugada syndrome 4 | 2019-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 233 of the CACNB2 protein (p.Val233Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. 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 CACNB2-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV003160538 | SCV003854510 | uncertain significance | Cardiovascular phenotype | 2022-11-15 | criteria provided, single submitter | clinical testing | The p.V233L variant (also known as c.697G>C), located in coding exon 7 of the CACNB2 gene, results from a G to C substitution at nucleotide position 697. The valine at codon 233 is replaced by leucine, an amino acid with highly similar 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. |