ClinVar

Description

The Q360E variant in the MFN2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q360E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q360E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In addition, this substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (T356A, T356S, K357N, H361Y, T362M, T362R, R364W, R364P, and R364Q) have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth disease or MFN2-related neuropathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, Q360E is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.