Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002008014 | SCV002264219 | uncertain significance | Brugada syndrome 4 | 2021-01-18 | 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"). This variant has not been reported in the literature in individuals with CACNB2-related conditions. This variant is present in population databases (rs753259405, ExAC 0.02%). This sequence change replaces arginine with cysteine at codon 573 of the CACNB2 protein (p.Arg573Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. |
| Ambry Genetics | RCV003170304 | SCV003911727 | uncertain significance | Cardiovascular phenotype | 2022-11-30 | criteria provided, single submitter | clinical testing | The p.R573C variant (also known as c.1717C>T), located in coding exon 13 of the CACNB2 gene, results from a C to T substitution at nucleotide position 1717. The arginine at codon 573 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available 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. |