Submissions for variant NM_001351132.2(PEX5):c.1462C>G (p.Pro488Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002585999	SCV002938170	uncertain significance	Peroxisome biogenesis disorder 2B	2023-07-17	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 488 of the PEX5 protein (p.Pro488Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1900914). 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 PEX5 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	RCV004749909	SCV005350879	uncertain significance	PEX5-related disorder	2024-07-17	no assertion criteria provided	clinical testing	The PEX5 c.1462C>G variant is predicted to result in the amino acid substitution p.Pro488Ala. To our knowledge, this variant has not been reported in the literature or in the large population database gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.