Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002043835 | SCV002312230 | uncertain significance | Brugada syndrome 4 | 2022-03-08 | criteria provided, single submitter | clinical testing | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 C0"). This variant is also known as D131G. This missense change has been observed in individual(s) with restrictive cardiomyopathy (PMID: 27662471). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 77 of the CACNB2 protein (p.Asp77Gly). |
Petrovsky National Research Centre of Surgery, |
RCV002043835 | SCV003918905 | uncertain significance | Brugada syndrome 4 | 2022-10-21 | criteria provided, single submitter | clinical testing | We observed a genetic variant c.392A>G (p.Asp131Gly) in the CACNB2 gene on WES data in a male 34-y.o. patient diagnosed with early repolarization syndrome (ERS), J-wave elevation, Brugada-like ECG, and VF induced during electrophysiological study (EPS). Substitution Asp to Gly affects SH3-domain of the regulatory beta-subunit of the Cav1.2 channel, and most of in silico tools predict the variant to be deleterious. This variant is not present in gnomAD database. In the absence of the family screening data and/or cellular functional studies, we could only classify the c.392A>G (p.Asp131Gly) as a variant of uncertain clinical significance. |