Submissions for variant NM_000466.3(PEX1):c.1351_1354dup (p.Asn452fs)

dbSNP: rs1792596054

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194279	SCV001363677	likely pathogenic	Peroxisome biogenesis disorder	2019-05-24	criteria provided, single submitter	clinical testing	Variant summary: PEX1 c.1351_1354dupGAGA (p.Asn452ArgfsX5) 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.2097dupT (p.Ile700fsX42), c.2916delA (p.Gly973fsX16)). The variant was absent in 250186 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1351_1354dupGAGA in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. 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 likely pathogenic.
Natera, Inc.	RCV001833751	SCV002076909	likely pathogenic	Zellweger spectrum disorders	2021-05-20	no assertion criteria provided	clinical testing