Total submissions: 4
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, |
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 |