Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001229889 | SCV001402350 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2019-10-12 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CDH1-related conditions. 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. 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 is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 509 of the CDH1 protein (p.Thr509Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. |