Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002005705 | SCV002273804 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-10-05 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 670 of the CDH1 protein (p.Met670Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. |
| Ambry Genetics | RCV004603129 | SCV005095398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | The p.M670I variant (also known as c.2010G>A), located in coding exon 13 of the CDH1 gene, results from a G to A substitution at nucleotide position 2010. The methionine at codon 670 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |