Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000205131 | SCV000259969 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-09-01 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 219863). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 138 of the CDH1 protein (p.Glu138Gly). |
| Ambry Genetics | RCV002327062 | SCV002629358 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-11 | criteria provided, single submitter | clinical testing | The p.E138G variant (also known as c.413A>G), located in coding exon 4 of the CDH1 gene, results from an A to G substitution at nucleotide position 413. The glutamic acid at codon 138 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004567455 | SCV005060060 | uncertain significance | Familial cancer of breast | 2024-03-11 | criteria provided, single submitter | clinical testing |