ClinVar Miner

Submissions for variant NM_000726.4(CACNB4):c.44C>G (p.Pro15Arg) (rs200662010)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186843 SCV000240414 uncertain significance not specified 2015-12-09 criteria provided, single submitter clinical testing p.Pro15Arg (CCG>CGG): c.44 C>G in exon 1 of the CACNB4 gene (NM_000726.2). The P15R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports P15R was observed in 26/8128 (0.3%) alleles from individuals of European background, and the 1000 Genomes Project reports P15R was observed in 1/120 (0.8%) alleles from individuals of Mexican background, indicating it may be a rare (benign) variant in these populations. The P15R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution alters a poorly conserved position in the predicted N-terminal region of the CACNB4 protein, and disease-associated mutations have not been reported in this region to date (Escayg et al., 2000; Ohmori et al., 2008). Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s).
Genetic Services Laboratory, University of Chicago RCV000186843 SCV000246840 likely benign not specified 2019-04-22 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000186843 SCV000339595 likely benign not specified 2016-02-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000384411 SCV000417257 likely benign Juvenile myoclonic epilepsy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000271279 SCV000417258 benign Episodic ataxia, type 5 2018-01-13 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.
Invitae RCV000471900 SCV000562363 likely benign Idiopathic generalized epilepsy 2020-11-12 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515246 SCV000611379 uncertain significance Epilepsy, idiopathic generalized 9; Episodic ataxia, type 5 2017-05-23 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000515246 SCV000809097 uncertain significance Epilepsy, idiopathic generalized 9; Episodic ataxia, type 5 2018-06-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000186843 SCV001474893 benign not specified 2020-08-12 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.