Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001235521 | SCV001408211 | uncertain significance | Mowat-Wilson syndrome | 2020-02-18 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ZEB2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 949 of the ZEB2 protein (p.Met949Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. 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. |
Gene |
RCV001760247 | SCV001990492 | uncertain significance | not provided | 2019-07-30 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV001235521 | SCV002045620 | uncertain significance | Mowat-Wilson syndrome | 2021-11-07 | criteria provided, single submitter | clinical testing |