Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000540402 | SCV000637702 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 390 of the CDH1 protein (p.Asn390Ser). This variant is not present in population databases (gnomAD no frequency). 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: 463702). 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. |
MGZ Medical Genetics Center | RCV002289758 | SCV002580283 | uncertain significance | Familial cancer of breast | 2021-10-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002330866 | SCV002630456 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-24 | criteria provided, single submitter | clinical testing | The p.N390S variant (also known as c.1169A>G), located in coding exon 9 of the CDH1 gene, results from an A to G substitution at nucleotide position 1169. The asparagine at codon 390 is replaced by serine, an amino acid with highly similar properties. This alteration was observed with an allele frequency of 0.0000 in 53 unselected male breast cancer patients and was observed with an allele frequency of 0.0001 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is not 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. |
Baylor Genetics | RCV002289758 | SCV005060057 | uncertain significance | Familial cancer of breast | 2024-03-19 | criteria provided, single submitter | clinical testing |