ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.2684G>A (p.Arg895His) (rs786205755)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170794 SCV000223349 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing p.Arg895His (CGC>CAC): c.2684 G>A in exon 20 of the CACNA1C gene (NM_000719.6). The Arg895His variant in the CACNA1C gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg895His results in a conservative amino acid substitution of of one positively charged amino acid with another at a position that is conserved across species. In silico analysis predicts Arg895His is probably damaging to the protein structure/function. The Arg895His variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with LQTS, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Arg895His is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Invitae RCV000465144 SCV000553014 uncertain significance Long QT syndrome 2016-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 895 of the CACNA1C protein (p.Arg895His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CACNA1C-related disease. ClinVar contains an entry for this variant (Variation ID: 190656). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.