Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001313342 | SCV001503834 | uncertain significance | Brugada syndrome 4 | 2022-10-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (rs768218683, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 60 of the CACNB2 protein (p.Pro60Ser). ClinVar contains an entry for this variant (Variation ID: 1014589). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNB2 protein function. |
| Ambry Genetics | RCV002412001 | SCV002716101 | uncertain significance | Cardiovascular phenotype | 2022-10-11 | criteria provided, single submitter | clinical testing | The p.P60S variant (also known as c.178C>T), located in coding exon 3 of the CACNB2 gene, results from a C to T substitution at nucleotide position 178. The proline at codon 60 is replaced by serine, an amino acid with 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. |