ClinVar

Description

This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 392 of the CYP27A1 protein (p.Glu392Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with cerebrotendinous xanthomatosis (PMID: 19373932). This variant is also known as E359A. ClinVar contains an entry for this variant (Variation ID: 500465). 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 expected to disrupt CYP27A1 protein function. This variant disrupts the p.Glu392 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP27A1-related conditions (PMID: 27455001), which suggests that this may be a clinically significant amino acid residue. 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.