ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.2435G>A (p.Arg812Gln)

gnomAD frequency: 0.00001  dbSNP: rs61753229
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
Counsyl RCV000670936 SCV000795858 likely pathogenic Peroxisome biogenesis disorder 4A (Zellweger); Peroxisome biogenesis disorder 4B 2017-11-21 criteria provided, single submitter clinical testing
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000857244 SCV000999831 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2019-03-05 criteria provided, single submitter clinical testing This variant was identified in combination with a second variant in trans in the same gene (PEX6 - composite heterozygosity) in a newborn patient with Zellweger syndrome
Invitae RCV001379858 SCV001577741 likely pathogenic Peroxisome biogenesis disorder 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 812 of the PEX6 protein (p.Arg812Gln). This variant is present in population databases (rs61753229, gnomAD 0.02%). This missense change has been observed in individuals with Zellweger syndrome (PMID: 10408779, 19877282). ClinVar contains an entry for this variant (Variation ID: 555170). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PEX6 protein function. Experimental studies have shown that this missense change affects PEX6 function (PMID: 10408779). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg812 amino acid residue in PEX6. Other variant(s) that disrupt this residue have been observed in individuals with PEX6-related conditions (PMID: 19877282), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV003472131 SCV004201528 likely pathogenic Heimler syndrome 2 2023-10-11 criteria provided, single submitter clinical testing

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.