ClinVar

Description

This variant is denoted p.Ser789Pro at the protein level, c.2365 T>C at the cDNA level, and results in a change of a Serine for a Proline (TCC>CCC) in exon 8 of the ZEB2 gene (NM_014795.3). The S789P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 S789P 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 that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in the ZEB2 gene are rare and have been identified in less than 2% of patients with Mowat-Wilson syndrome (Garavelli et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in RETT-EPI panel(s).