Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000223173 | SCV000279995 | pathogenic | not provided | 2017-11-27 | criteria provided, single submitter | clinical testing | The C50F pathogenic variant in the MPZ gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This 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 C50F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the extracellular domain that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same (C50G, C50W) and nearby (L48V, L48P, L48Q, S51F, S51C) residues have been reported in the Human Gene Mutation Database in association with MPZ-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret C50F as a pathogenic variant |