Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000477539 | SCV000552984 | uncertain significance | Brugada syndrome 4 | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 81 of the CACNB2 protein (p.Val81Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV004022884 | SCV005032068 | uncertain significance | Cardiovascular phenotype | 2023-09-26 | criteria provided, single submitter | clinical testing | The p.V81L variant (also known as c.241G>T), located in coding exon 3 of the CACNB2 gene, results from a G to T substitution at nucleotide position 241. The valine at codon 81 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |