ClinVar Miner

Submissions for variant NM_000097.7(CPOX):c.395C>T (p.Ala132Val) (rs147219463)

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
Illumina Clinical Services Laboratory,Illumina RCV000379879 SCV000446663 benign Hereditary coproporphyria 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.
GeneDx RCV000523448 SCV000618892 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing The A132V variant in the CPOX gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 41/61,204 alleles (0.066%) from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The A132V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution occurs at a position that is not conserved across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. The A132V variant is reported as likely benign in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000446663.2; Landrum et al., 2016). We interpret A132V as a variant of uncertain significance.
Invitae RCV000523448 SCV001204936 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 132 of the CPOX protein (p.Ala132Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs147219463, ExAC 0.07%). This variant has not been reported in the literature in individuals with CPOX-related disease. ClinVar contains an entry for this variant (Variation ID: 346984). 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. 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.