Submissions for variant NM_001127649.3(PEX26):c.571C>T (p.Arg191Trp)

gnomAD frequency: 0.00011  dbSNP: rs150451390

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000593848	SCV000703057	uncertain significance	not provided	2016-10-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765605	SCV000896928	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001140192	SCV001300418	uncertain significance	Peroxisome biogenesis disorder 7A (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.
Invitae	RCV000765605	SCV001403242	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 191 of the PEX26 protein (p.Arg191Trp). This variant is present in population databases (rs150451390, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PEX26-related conditions. ClinVar contains an entry for this variant (Variation ID: 498175). 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 PEX26 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.
Ambry Genetics	RCV002532407	SCV003722547	uncertain significance	Inborn genetic diseases	2022-12-15	criteria provided, single submitter	clinical testing	The c.571C>T (p.R191W) alteration is located in exon 4 (coding exon 3) of the PEX26 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the arginine (R) at amino acid position 191 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.