Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159469 | SCV000209420 | uncertain significance | not provided | 2013-10-14 | criteria provided, single submitter | clinical testing | This variant is denoted p.His321Pro at the protein level, c.962 A>C at the cDNA level and results in the change of a Histidine to a Proline (CAT>CCT) in exon 8 of the ZEB2 gene (NM_014795.2). The His321Pro missense change 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. This variant is a non-conservative amino acid substitution of a positively charged Histidine residue with an uncharged, non-polar Proline residue, and the addition of a Proline, which has a unique ring structure, may alter the secondary structure of the protein. It alters a position in the ZEB2 protein that is highly conserved across species and 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 His321Pro is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |