ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.2258C>T (p.Ala753Val)

gnomAD frequency: 0.00001  dbSNP: rs200355966
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485255 SCV000573475 uncertain significance not provided 2022-07-18 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001210428 SCV001381915 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 754 of the CACNA1A protein (p.Ala754Val). This variant is present in population databases (rs200355966, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 423741). 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 expected to disrupt CACNA1A protein function with a positive predictive value of 95%. 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.
Ambry Genetics RCV002446946 SCV002733392 uncertain significance Inborn genetic diseases 2017-09-25 criteria provided, single submitter clinical testing The p.A754V variant (also known as c.2261C>T), located in coding exon 18 of the CACNA1A gene, results from a C to T substitution at nucleotide position 2261. The alanine at codon 754 is replaced by valine, an amino acid with similar properties. This amino acid position is highly 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.

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.