ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.3689_3692GTCA[1] (p.Gln1231fs) (rs769836601)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169360 SCV000220731 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-09-25 criteria provided, single submitter literature only
Invitae RCV001201345 SCV000934668 pathogenic Zellweger syndrome 2019-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1231Hisfs*3) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769836601, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another PEX1 variant in individuals affected with Zellweger syndrome spectrum disorder (PMID: 16141001, 19105186). This variant is also known as c.3691_3694delCAGT in the literature. ClinVar contains an entry for this variant (Variation ID: 188981). Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001004312 SCV001163193 pathogenic Peroxisome biogenesis disorder 1A (Zellweger); Peroxisome biogenesis disorder 1B criteria provided, single submitter clinical testing
GeneDx RCV001008785 SCV001168577 pathogenic not provided 2019-01-22 criteria provided, single submitter clinical testing The c.3693_3696delGTCA variant in the PEX1 gene has been reported previously in the homozygous state and with another PEX1 gene variant, in unrelated individuals with Zellweger syndrome (Rosewich et al., 2005; Yik et al., 2009). The c.3693_3696delGTCA variant causes a frameshift starting with codon Glutamine 1231, changes this amino acid to a Histidine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Gln1231HisfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3693_3696delGTCA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.3693_3696delGTCA as a pathogenic variant.

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