ClinVar Miner

Submissions for variant NM_020361.5(CPA6):c.707C>T (p.Pro236Leu) (rs201552815)

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
GeneDx RCV000483962 SCV000573366 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing The P236L variant in the CPA6 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P236L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P236L 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 silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P236L as a variant of uncertain significance.
Invitae RCV000692380 SCV000820200 uncertain significance Febrile seizures, familial, 11 2018-02-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 236 of the CPA6 protein (p.Pro236Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs201552815, ExAC 0.009%). This variant has not been reported in the literature in individuals with CPA6-related disease. ClinVar contains an entry for this variant (Variation ID: 423645). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.