Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159470 | SCV000209421 | uncertain significance | not provided | 2013-03-13 | criteria provided, single submitter | clinical testing | This variant is denoted p.Val428Ala at the protein level, c.1283 T>C at the cDNA level and results in the change of a Valine for an Alanine (GTT>GCT) in exon 8 of the ZEB2 gene (NM_014795.2). The Val428Ala 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 or among the various ethnic groups studied in the 1000 Genomes Project, indicating it is not a common benign variant in these populations. The amino acid substitution is conservative, as both Valine and Alanine are uncharged, non-polar amino acid residues and Val428Ala alters a conserved position in the ZEB2 protein. However, in-silico algorithms are not consistent in their predictions of whether Val428Ala is damaging to the structure/function of the protein. Additionally, 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 Val428Ala is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Fulgent Genetics, |
RCV000764261 | SCV000895274 | uncertain significance | Mowat-Wilson syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000764261 | SCV002045630 | uncertain significance | Mowat-Wilson syndrome | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000764261 | SCV004286171 | uncertain significance | Mowat-Wilson syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 428 of the ZEB2 protein (p.Val428Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZEB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 181731). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |