Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160392 | SCV000210915 | uncertain significance | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer and no known personal or family history of gastric cancer in a study of CDH1 variants (PMID: 36436516); This variant is associated with the following publications: (PMID: 22722829, 15235021, 22850631, 36436516) |
Labcorp Genetics |
RCV000206225 | SCV000260134 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 493 of the CDH1 protein (p.Val493Leu). This variant is present in population databases (rs730881666, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 182398). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV000221777 | SCV000273932 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | The p.V493L variant (also known as c.1477G>C), located in coding exon 10 of the CDH1 gene, results from a G to C substitution at nucleotide position 1477. The valine at codon 493 is replaced by leucine, an amino acid with highly 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. |
Color Diagnostics, |
RCV000221777 | SCV000689455 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-19 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with leucine at codon 493 of the CDH1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 8/251488 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800470 | SCV002046284 | uncertain significance | not specified | 2020-10-16 | criteria provided, single submitter | clinical testing | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000206225 | SCV003926800 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | Not applicable criteria (PMID: 30311375) |
Baylor Genetics | RCV003462088 | SCV004215639 | uncertain significance | Familial cancer of breast | 2023-09-24 | criteria provided, single submitter | clinical testing | |
True Health Diagnostics | RCV000221777 | SCV000886678 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-13 | no assertion criteria provided | clinical testing |