Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463627 | SCV000552985 | uncertain significance | Brugada syndrome 4 | 2016-04-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs148674271, ExAC 0.04%) but has not been reported in the literature in individuals with a CACNB2-related disease. This sequence change replaces glutamic acid with glycine at codon 305 of the CACNB2 protein (p.Glu305Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002374812 | SCV002688619 | likely benign | Cardiovascular phenotype | 2023-05-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Fulgent Genetics, |
RCV000463627 | SCV002816598 | uncertain significance | Brugada syndrome 4 | 2021-11-21 | criteria provided, single submitter | clinical testing |