ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.3230C>T (p.Ala1077Val) (rs199512932)

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
Ambry Genetics RCV000719480 SCV000850347 likely benign History of neurodevelopmental disorder 2016-12-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Athena Diagnostics Inc RCV000423840 SCV000612526 likely benign not specified 2017-04-20 criteria provided, single submitter clinical testing
GeneDx RCV000423840 SCV000526293 likely benign not specified 2016-04-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000559097 SCV000656747 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1077 of the CACNA1A protein (p.Ala1077Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs199512932, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CACNA1A-related disease. ClinVar contains an entry for this variant (Variation ID: 385136). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.