ClinVar Miner

Submissions for variant NM_000726.5(CACNB4):c.1310G>A (p.Arg437Gln)

gnomAD frequency: 0.00001  dbSNP: rs751754026
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000687371 SCV000814935 uncertain significance Idiopathic generalized epilepsy 2018-12-17 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 (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. This variant has not been reported in the literature in individuals with CACNB4-related disease. This variant is present in population databases (rs751754026, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces arginine with glutamine at codon 437 of the CACNB4 protein (p.Arg437Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine.
Illumina Laboratory Services, Illumina RCV001136144 SCV001295965 benign Episodic ataxia type 5 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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.