Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000532715 | SCV000627554 | uncertain significance | Long QT syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1613 of the CACNA1C protein (p.Val1613Ile). This variant is present in population databases (rs757629968, 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: 456973). 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. 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. |
| ARUP Laboratories, |
RCV001002112 | SCV001159959 | uncertain significance | not specified | 2018-10-05 | criteria provided, single submitter | clinical testing | The p.Val1613Ile variant (rs757629968) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.0008 percent (identified on 2 out of 245,050 chromosomes) and has been reported to the ClinVar database (Variation ID: 456973). The valine at position 1613 is highly conserved and computational analyses of the effects of the p.Val1613Ile variant on protein structure and function provide conflicting results (SIFT: deleterious, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Val1613Ile variant with certainty. |
| Ambry Genetics | RCV003362826 | SCV004053840 | uncertain significance | Cardiovascular phenotype | 2023-07-03 | criteria provided, single submitter | clinical testing | The p.V1613I variant (also known as c.4837G>A), located in coding exon 40 of the CACNA1C gene, results from a G to A substitution at nucleotide position 4837. The valine at codon 1613 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |