Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781212 | SCV000919104 | uncertain significance | not specified | 2018-03-30 | criteria provided, single submitter | clinical testing | Variant summary: CDH1 c.442G>A (p.Gly148Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 121384 control chromosomes (ExAC). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.442G>A in individuals affected with Hereditary Diffuse Gastric Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV000801723 | SCV000941515 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-04-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 148 of the CDH1 protein (p.Gly148Ser). 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: 633150). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. 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. |
| Color Diagnostics, |
RCV001182395 | SCV001347830 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-23 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478484 | SCV004220833 | uncertain significance | not provided | 2023-03-16 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Ambry Genetics | RCV001182395 | SCV005095400 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | The p.G148S variant (also known as c.442G>A), located in coding exon 4 of the CDH1 gene, results from a G to A substitution at nucleotide position 442. The glycine at codon 148 is replaced by serine, an amino acid with 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. |