ClinVar

Description

The E544Q variant of uncertain significance in the ATP7A gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. E544Q was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, and was not observed with any significant frequency in the Exome Aggregation Consortium, indicating it is not a common benign variant in these populations. The E544Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. And while this substitution occurs at a position that is conserved in mammals, Q544 is the native residue in at least two species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, no pathogenic missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants.