Submissions for variant NM_000466.3(PEX1):c.3031G>A (p.Val1011Met)

gnomAD frequency: 0.00028  dbSNP: rs141650598

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000298949	SCV000342312	likely benign	not specified	2018-02-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000345924	SCV000470501	uncertain significance	Peroxisome biogenesis disorder 1A (Zellweger)	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000766589	SCV000576500	uncertain significance	not provided	2017-05-02	criteria provided, single submitter	clinical testing	The V1011M variant in the PEX1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V1011M variant is observed in 47/16422 (0.29%) alleles from individuals of South Asian background, including 1 homozygous individual, in the ExAC dataset (Lek et al., 2016). The V1011M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V1011M as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001277301	SCV001024312	benign	Zellweger spectrum disorders	2024-12-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000766589	SCV001144901	benign	not provided	2019-03-21	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000345924	SCV001652857	likely benign	Peroxisome biogenesis disorder 1A (Zellweger)	2021-05-18	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001277301	SCV001464242	benign	Zellweger spectrum disorders	2020-06-01	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003977800	SCV004795877	likely benign	PEX1-related disorder	2019-05-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).