Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000351940 | SCV000437325 | uncertain significance | Peroxisome biogenesis disorder 7A (Zellweger) | 2017-04-28 | criteria provided, single submitter | clinical testing | The PEX26 c.134T>C (p.Leu45Pro) missense variant was reported in a compound heterozygous state with a second missense variant in one individual with infantile Refsum disease, which is part of the Zellweger spectrum (Matsumoto et al. 2003). Control data are not available and allele frequency information for this variant is not reported in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Expression of the p.Leu45Pro variant in a PEX26-deficient CHO cell line showed that the variant did not restore impaired peroxisome biogenesis (Matsumoto et al. 2003, Weller et al. 2005) and interfered with interactions with other PEX proteins (Furuki et al. 2006; Tamura et al. 2014). Based on the evidence, the p.Leu45Pro variant is classified as a variant of unknown significance but suspicious for pathogenicity for Zellweger syndrome spectrum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV001298874 | SCV001487945 | uncertain significance | Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B | 2022-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 45 of the PEX26 protein (p.Leu45Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with infantile Refsum disease (PMID: 12851857). ClinVar contains an entry for this variant (Variation ID: 2157). 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. Experimental studies have shown that this missense change affects PEX26 function (PMID: 12851857, 16257970, 25016021). 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. |
Baylor Genetics | RCV000351940 | SCV004201496 | likely pathogenic | Peroxisome biogenesis disorder 7A (Zellweger) | 2023-10-30 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000002240 | SCV000022398 | pathogenic | Peroxisome biogenesis disorder 7B | 2003-08-01 | no assertion criteria provided | literature only |