ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1500_1521del (p.Leu501fs) (rs1555762855)

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
Athena Diagnostics Inc RCV000516261 SCV000612508 pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing
Invitae RCV000526917 SCV000656713 pathogenic Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2017-05-23 criteria provided, single submitter clinical testing This sequence change deletes 22 nucleotides from exon 11 of the CACNA1A mRNA (c.1503_1524del), causing a frameshift at codon 502. This creates a premature translational stop signal (p.Leu502Thrfs*19) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 14718690, 10371528). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000516261 SCV001168208 likely pathogenic not provided 2018-10-29 criteria provided, single submitter clinical testing The c.1503_1524del22 variant in the CACNA1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1503_1524del22 variant causes a frameshift starting with codon Leucine 502, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 19 of the new reading frame, denoted p.Leu502ThrfsX19. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1503_1524del22 variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1503_1524del22 as a likely pathogenic variant.

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.