ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.1841del (p.Leu614fs) (rs863225083)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674727 SCV000800118 likely pathogenic Peroxisome biogenesis disorder 4a (zellweger); Peroxisome biogenesis disorder 4B 2018-05-23 criteria provided, single submitter clinical testing
GeneDx RCV001008824 SCV001168627 pathogenic not provided 2018-12-13 criteria provided, single submitter clinical testing The c.1841delT variant in the PEX6 gene has been reported previously in twin siblings with Heimler syndrome who also harbored a PEX6 missense variant, although parental studies were not performed to determine the phase of these two variants (Ratbi et al., 2015). Functional studies using in vitro transfection of the c.1841delT variant showed minimal functional complementation of peroxisome biogenesis in peroxisome deficient cells. The c.1841delT variant causes a frameshift starting with codon Leucine 614, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Leu614ArgfsX5. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1841delT variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1841delT as a pathogenic variant.
OMIM RCV000201289 SCV000256086 pathogenic Heimler syndrome 2 2015-10-01 no assertion criteria provided literature only

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