Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001229088 | SCV001401524 | uncertain significance | Long QT syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 956311). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. This variant is present in population databases (rs754046062, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 888 of the CACNA1C protein (p.Arg888Ser). |
Ambry Genetics | RCV003365271 | SCV004053838 | uncertain significance | Cardiovascular phenotype | 2023-06-22 | criteria provided, single submitter | clinical testing | The p.R888S variant (also known as c.2664G>C) is located in coding exon 20 of the CACNA1C gene. The arginine at codon 888 is replaced by serine, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 20. This amino acid position is not 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. |
Prevention |
RCV003405417 | SCV004113542 | uncertain significance | CACNA1C-related disorder | 2022-08-19 | criteria provided, single submitter | clinical testing | The CACNA1C c.2664G>C variant is predicted to result in the amino acid substitution p.Arg888Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0056% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-2705040-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |