Submissions for variant NM_000466.3(PEX1):c.3419_3424del (p.Asn1140_Gly1141del)

dbSNP: rs758076338

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000732861	SCV000860857	uncertain significance	not provided	2018-04-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001247717	SCV001421157	uncertain significance	Zellweger spectrum disorders	2025-01-13	criteria provided, single submitter	clinical testing	This variant, c.3419_3424del, results in the deletion of 2 amino acid(s) of the PEX1 protein (p.Asn1140_Gly1141del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758076338, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 596889). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001731913	SCV001984006	uncertain significance	not specified	2020-05-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000732861	SCV005195966	uncertain significance	not provided		criteria provided, single submitter	not provided
GeneDx	RCV000732861	SCV005386363	uncertain significance	not provided	2024-01-12	criteria provided, single submitter	clinical testing	In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000732861	SCV001951562	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000732861	SCV001967800	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001247717	SCV002076811	uncertain significance	Zellweger spectrum disorders	2018-05-09	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003396307	SCV004103764	uncertain significance	PEX1-related disorder	2024-05-22	no assertion criteria provided	clinical testing	The PEX1 c.3419_3424del6 variant is predicted to result in an in-frame deletion (p.Asn1140_Gly1141del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.10% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-92120599-GTTCCAT-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.