Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001897971 | SCV002157821 | uncertain significance | Brugada syndrome 4 | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 457 of the CACNB2 protein (p.Arg457Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals 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: "Deleterious"; 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 | RCV002386670 | SCV002696094 | uncertain significance | Cardiovascular phenotype | 2023-06-23 | criteria provided, single submitter | clinical testing | The p.R457C variant (also known as c.1369C>T), located in coding exon 13 of the CACNB2 gene, results from a C to T substitution at nucleotide position 1369. The arginine at codon 457 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001897971 | SCV003828865 | uncertain significance | Brugada syndrome 4 | 2020-03-13 | criteria provided, single submitter | clinical testing |