Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002934057 | SCV003278637 | uncertain significance | Brugada syndrome 4 | 2021-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 499 of the CACNB2 protein (p.Glu499Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs770237131, ExAC 0.009%). This missense change has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 22840528). 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"). 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. |