Submissions for variant NM_000466.3(PEX1):c.1886_1887del (p.Asp628_Cys629insTer)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000669833	SCV000794624	likely pathogenic	Peroxisome biogenesis disorder 1A (Zellweger)	2017-10-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001008714	SCV001168494	likely pathogenic	not provided	2018-12-06	criteria provided, single submitter	clinical testing	The c.1886_1887delGT variant in the PEX1 gene has been reported previously in the heterozygous state in a fibroblast cell line derived from a patient with Zellweger syndrome spectrum (Ebberink et al., 2011); it is unclear if this cell line harbored a second PEX1 variant. The c.1886_1887delGT variant causes a frameshift start at codon Cysteine 629, changing this amino acid to a premature stop codon, denoted p.C629Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1886_1887delGT variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1886_1887delGT as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001277055	SCV003440067	pathogenic	Zellweger spectrum disorders	2022-12-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 554241). This premature translational stop signal has been observed in individual(s) with Zellweger spectrum disorder (PMID: 21031596). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Cys629*) 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: 9398847, 16086329, 16141001, 21031596, 26387595, 31831025).
Baylor Genetics	RCV004568532	SCV005055214	pathogenic	Heimler syndrome 1	2024-03-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001277055	SCV001463790	likely pathogenic	Zellweger spectrum disorders	2020-09-16	no assertion criteria provided	clinical testing

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