ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.4786G>A (p.Ala1596Thr)

gnomAD frequency: 0.00001  dbSNP: rs769043258
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038794 SCV001202288 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1597 of the CACNA1A protein (p.Ala1597Thr). This variant is present in population databases (rs769043258, gnomAD 0.004%). 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: 837454). 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 CACNA1A protein function with a negative 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.
GeneDx RCV001563380 SCV001786311 uncertain significance not provided 2020-02-03 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen RCV001563380 SCV002498434 uncertain significance not provided 2022-01-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001563380 SCV002770696 uncertain significance not provided 2021-08-23 criteria provided, single submitter clinical testing

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.