Submissions for variant NM_000287.4(PEX6):c.1612C>T (p.Arg538Cys)

gnomAD frequency: 0.00002  dbSNP: rs374253469

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001932577	SCV002135389	uncertain significance	Peroxisome biogenesis disorder	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 538 of the PEX6 protein (p.Arg538Cys). This variant is present in population databases (rs374253469, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367788). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PEX6 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	RCV004738407	SCV005364055	uncertain significance	PEX6-related disorder	2024-04-19	no assertion criteria provided	clinical testing	The PEX6 c.1612C>T variant is predicted to result in the amino acid substitution p.Arg538Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.