Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000477423 | SCV000545419 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 321 of the CDH1 protein (p.Arg321Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 406641). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506969 | SCV000601001 | uncertain significance | not specified | 2017-04-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002379431 | SCV002693856 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-09 | criteria provided, single submitter | clinical testing | The p.R321S variant (also known as c.963G>C), located in coding exon 7 of the CDH1 gene, results from a G to C substitution at nucleotide position 963. The arginine at codon 321 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is poorly 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. |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000477423 | SCV003926709 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2 (PMID: 30311375) |