Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000170814 | SCV000223369 | uncertain significance | not provided | 2013-12-09 | criteria provided, single submitter | clinical testing | p.Gly1662Arg (GGG>AGG): c.4984 G>A in exon 41 of the CACNA1C gene (NM_000719.6). The Gly1662Arg variant in the CACNA1C gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Gly1662Arg results in a non-conservative amino acid substitution of a non-polar Glycine with a positively charged Arginine at a position that is conserved across species. In silico analysis predicts Gly1662Arg is damaging to the protein structure/function. The Gly1662Arg variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no mutations in nearby residues have been reported in association with arrhythmia, suggesting this region of the protein may be tolerant to change. With the clinical and molecular information available at this time, we cannot definitively determine if Gly1662Arg is a disease-causing mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s). |
| Labcorp Genetics |
RCV001367040 | SCV001563372 | uncertain significance | Long QT syndrome | 2024-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1662 of the CACNA1C protein (p.Gly1662Arg). This variant is present in population databases (rs778011390, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 190676). Invitae Evidence 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 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265657 | SCV002548096 | uncertain significance | not specified | 2022-05-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345573 | SCV002645632 | uncertain significance | Cardiovascular phenotype | 2020-11-20 | criteria provided, single submitter | clinical testing | The p.G1662R variant (also known as c.4984G>A), located in coding exon 41 of the CACNA1C gene, results from a G to A substitution at nucleotide position 4984. The glycine at codon 1662 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002492700 | SCV002800124 | uncertain significance | Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 | 2021-08-31 | criteria provided, single submitter | clinical testing |