Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001373922 | SCV001570666 | uncertain significance | Brugada syndrome 4 | 2021-06-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 171 of the CACNB2 protein (p.Ile171Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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: "Benign"; 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 (rs772796787, ExAC 0.006%). |
| ARUP Laboratories, |
RCV001373922 | SCV002049987 | uncertain significance | Brugada syndrome 4 | 2020-10-04 | criteria provided, single submitter | clinical testing | The CACNB2 c.512T>C; p.Ile171Thr variant (rs772796787), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The isoleucine at codon 171 is moderately conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Based on the available information, the clinical significance of this variant is uncertain. |