Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002029144 | SCV002297456 | uncertain significance | Brugada syndrome 4 | 2023-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 526 of the CACNB2 protein (p.Asp526Gly). 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. ClinVar contains an entry for this variant (Variation ID: 1504916). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (rs762715765, gnomAD 0.008%). |
| Ambry Genetics | RCV002398095 | SCV002704128 | uncertain significance | Cardiovascular phenotype | 2022-03-16 | criteria provided, single submitter | clinical testing | The p.D526G variant (also known as c.1577A>G), located in coding exon 13 of the CACNB2 gene, results from an A to G substitution at nucleotide position 1577. The aspartic acid at codon 526 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |