Submissions for variant NM_000466.3(PEX1):c.3483G>C (p.Leu1161Phe)

gnomAD frequency: 0.00001  dbSNP: rs375607384

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001979003	SCV002227470	uncertain significance	Zellweger spectrum disorders	2022-06-04	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1161 of the PEX1 protein (p.Leu1161Phe). This variant is present in population databases (rs375607384, gnomAD 0.01%). 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: 1441026). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PEX1 protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV004753446	SCV005353945	uncertain significance	PEX1-related disorder	2024-04-30	no assertion criteria provided	clinical testing	The PEX1 c.3483G>C variant is predicted to result in the amino acid substitution p.Leu1161Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.