Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001561495 | SCV001784114 | uncertain significance | not provided | 2020-09-25 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Invitae | RCV001865981 | SCV002124647 | uncertain significance | Long QT syndrome | 2021-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with arginine at codon 1021 of the CACNA1C protein (p.Cys1021Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with long QT syndrome (Invitae). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys1021 amino acid residue in CACNA1C. Other variant(s) that disrupt this residue have been observed in individuals with CACNA1C-related conditions (PMID: 32161207), which suggests that this may be a clinically significant amino acid residue. 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. |
Dept of Medical Biology, |
RCV003318403 | SCV004021970 | likely pathogenic | Timothy syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PS2_Moderate, PM2, PP2, PP3 |