ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.4055C>T (p.Pro1352Leu)

dbSNP: rs1064794808
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
GeneDx RCV000486354 SCV000569989 pathogenic not provided 2017-03-22 criteria provided, single submitter clinical testing The P1353L variant in the CACN1A gene has been reported previously as a presumed de novo finding in a child with global developmental delay and hypotonia (Weyhrauch et al., 2015; Lazaridis et al., 2016). The P1353L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1353L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In vitro analysis of P1353L demonstrates that this variant results in nearly complete loss of calcium channel function (Weyhrauch et al., 2015). Furthermore, missense variants in nearby residues (R1349Q, V1350L) have been reported in the Human Gene Mutation Database in association with CACNA1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret P1353L as a pathogenic variant.
Wendy Chung Laboratory, Columbia University Medical Center RCV002227167 SCV002506529 pathogenic Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 52 2022-03-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV003152605 SCV003841212 pathogenic Developmental and epileptic encephalopathy, 42 criteria provided, single submitter clinical testing
Baylor Genetics RCV000679938 SCV000807372 uncertain significance Episodic ataxia type 2 2017-09-01 flagged submission clinical testing Likely pathogenicity based on finding it once in our laboratory de novo in a 3-year-old male with global delays, axial hypotonia, limb hypertonia, ataxia, spasticity, myoclonus, pes planus, vision loss, coxa valga, kyphosis.

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.