Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001893716 | SCV002167556 | uncertain significance | Brugada syndrome 4 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 186 of the CACNB2 protein (p.Pro186Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs750627674, ExAC 0.04%). 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: "Tolerated"; 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 | RCV002343984 | SCV002650017 | uncertain significance | Cardiovascular phenotype | 2018-06-07 | criteria provided, single submitter | clinical testing | The p.P186A variant (also known as c.556C>G), located in coding exon 6 of the CACNB2 gene, results from a C to G substitution at nucleotide position 556. The proline at codon 186 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |