ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2730del (p.Leu910fs)

gnomAD frequency: 0.00002  dbSNP: rs61750423
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169346 SCV000220714 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-09-19 criteria provided, single submitter literature only
Invitae RCV001376586 SCV001211648 pathogenic Zellweger spectrum disorders 2024-01-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu910Phefs*51) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 21031596, 26387595, 31831025). This variant is present in population databases (rs61750423, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 11389485, 16141001). ClinVar contains an entry for this variant (Variation ID: 188971). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193614 SCV001362562 pathogenic Peroxisome biogenesis disorder 2019-06-04 criteria provided, single submitter clinical testing Variant summary: PEX1 c.2730delA (p.Leu910PhefsX51) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.2916delA, p.Gly973fsX16). The variant allele was found at a frequency of 8e-06 in 250798 control chromosomes (gnomAD). The variant, c.2730delA, has been reported in the literature in multiple individuals affected with Zellweger Syndrome (Walter_2001, Ebberink_2010). These data indicate that the variant is very likely to be associated with disease. Additionally, Walter_2001 reports two homozygous patients who lacked PEX1 completely, exhibited fully developed classical ZS with no import of peroxisomal matrix proteins, strongly elevated levels of VLCFA, and almost no DHAPAT activity in fibroblasts. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001726016 SCV001962062 pathogenic not provided 2021-11-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003474907 SCV004203284 pathogenic Heimler syndrome 1 2023-09-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV001376586 SCV002076847 pathogenic Zellweger spectrum disorders 2017-03-17 no assertion criteria provided clinical testing

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