ClinVar Miner

Submissions for variant NM_001127649.3(PEX26):c.353C>G (p.Pro118Arg) (rs61752135)

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 RCV000519883 SCV000617411 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing The P118R variant in the PEX26 gene has been reported previously in an individual with peroxisome biogenesis disorders in the Zellweger syndrome spectrum who was heterozygous for the P118R variant and another variant (Steinberg et al., 2004). The P118R variant is not observed in large population cohorts (Lek et al., 2016). The P118R 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. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P118R as a variant of uncertain significance.
Invitae RCV001071380 SCV001236682 uncertain significance Peroxisome biogenesis disorder 7A; Peroxisome biogenesis disorder 7B 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 118 of the PEX26 protein (p.Pro118Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with PEX26-related peroxisomal biogenesis disorder (PMID: 15542397). ClinVar contains an entry for this variant (Variation ID: 449363). 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 disruptive, 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.