Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001897594 | SCV002149234 | uncertain significance | Brugada syndrome 4 | 2022-08-22 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1382333). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 476 of the CACNB2 protein (p.His476Pro). |
| Ambry Genetics | RCV002388759 | SCV002697418 | uncertain significance | Cardiovascular phenotype | 2021-09-07 | criteria provided, single submitter | clinical testing | The p.H476P variant (also known as c.1427A>C), located in coding exon 13 of the CACNB2 gene, results from an A to C substitution at nucleotide position 1427. The histidine at codon 476 is replaced by proline, 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. |