ClinVar

Description

This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 466 of the RECQL4 protein (p.Pro466Ala). This variant is present in population databases (rs562809072, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 407031). 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 RECQL4 protein function. This variant disrupts the p.Pro466 amino acid residue in RECQL4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18504617, 18716613, 23238538, 33046774). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.