Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002317477 | SCV000850867 | uncertain significance | Cardiovascular phenotype | 2017-04-18 | criteria provided, single submitter | clinical testing | The p.D1078E variant (also known as c.3234C>A), located in coding exon 26 of the CACNA1C gene, results from a C to A substitution at nucleotide position 3234. The aspartic acid at codon 1078 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001346445 | SCV001540650 | uncertain significance | Long QT syndrome | 2023-01-17 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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: 589764). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. This variant is present in population databases (rs111606207, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1078 of the CACNA1C protein (p.Asp1078Glu). |