Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413249 | SCV000491950 | uncertain significance | not specified | 2016-11-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ZEB2 gene. The F144I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant 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 F144I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Phenylalanine are tolerated across species. Missense variants in the ZEB2 gene are rare and have been identified in less than 2% of patients with Mowat- Wilson syndrome (Garavelli et al., 2009). Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV000799160 | SCV000938812 | uncertain significance | Mowat-Wilson syndrome | 2024-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 144 of the ZEB2 protein (p.Phe144Ile). This variant is present in population databases (no rsID available, gnomAD 0.009%). 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: 373361). 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. |
| Genome- |
RCV000799160 | SCV002045635 | uncertain significance | Mowat-Wilson syndrome | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004022170 | SCV004983776 | likely benign | Inborn genetic diseases | 2024-03-08 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |