Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002036493 | SCV002314394 | uncertain significance | Brugada syndrome 4 | 2022-02-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 117 of the CACNB2 protein (p.Gly117Arg). This variant is present in population databases (rs766267727, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |
Prevention |
RCV003403662 | SCV004105255 | uncertain significance | CACNB2-related disorder | 2023-02-14 | criteria provided, single submitter | clinical testing | The CACNB2 c.349G>A variant is predicted to result in the amino acid substitution p.Gly117Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-18789795-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV004044796 | SCV005032040 | uncertain significance | Cardiovascular phenotype | 2024-03-11 | criteria provided, single submitter | clinical testing | The p.G117R variant (also known as c.349G>A), located in coding exon 4 of the CACNB2 gene, results from a G to A substitution at nucleotide position 349. The glycine at codon 117 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |