Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001218523 | SCV001390408 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-05-17 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 947445). 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 valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 477 of the CDH1 protein (p.Val477Met). |
Gene |
RCV001558141 | SCV001780026 | uncertain significance | not provided | 2019-11-20 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002393519 | SCV002701032 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing | The p.V477M variant (also known as c.1429G>A), located in coding exon 10 of the CDH1 gene, results from a G to A substitution at nucleotide position 1429. The valine at codon 477 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |