Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413738 | SCV000492085 | uncertain significance | not specified | 2016-11-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CACNA1C gene. The R1123C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1123C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1123C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this variant has not been identified in a significant number of affected individuals, and there are no functional studies or segregation data available to clarify the role of this variant in disease. |
| Labcorp Genetics |
RCV003532095 | SCV004290644 | uncertain significance | Long QT syndrome | 2023-07-13 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1C protein function. 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. ClinVar contains an entry for this variant (Variation ID: 373491). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1123 of the CACNA1C protein (p.Arg1123Cys). |