ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.170T>C (p.Leu57Pro) (rs61752140)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778791 SCV000915162 likely pathogenic Peroxisome biogenesis disorder 4a (zellweger) 2017-10-24 criteria provided, single submitter clinical testing The PEX6 c.170T>C (p.Leu57Pro) missense variant has been reported in at least two studies in a homozygous state in two patients with possible Zellweger syndrome and in a compound heterozygous state in one patient (Imamura et al. 2000; Ebberink et al. 2010). This variant was absent from 200 control chromosomes and is not found in the 1000 Genomes Project, Exome Sequencing Project, Exome Aggregation Consortium, or Genome Aggregation Database. Patient fibroblasts showed a decrease in peroxisomes at 37°C (5% of wildtype) and at 30°C (40% of wildtype). In CHO cells transfected with p.Leu57Pro variant PEX6, similar results were observed. The activity of enzymes involved in beta-oxidation and plasmalogen synthesis was elevated in patient fibroblasts and in CHO cells compared to controls. Taken together, the authors suggest that the p.Leu57Pro variant may result in faulty peroxisome assembly (Imamura et al. 2000). Based on the collective evidence, the p.Leu57Pro variant is classified as likely pathogenic for Zellweger syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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