Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001324150 | SCV001515093 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-01-27 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1024018). 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 threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 679 of the CDH1 protein (p.Thr679Asn). |
| Sema4, |
RCV002258202 | SCV002529102 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-19 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002258202 | SCV002723015 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-14 | criteria provided, single submitter | clinical testing | The p.T679N variant (also known as c.2036C>A), located in coding exon 13 of the CDH1 gene, results from a C to A substitution at nucleotide position 2036. The threonine at codon 679 is replaced by asparagine, an amino acid with similar properties. This variant was reported in 0/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). 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. |
| Gene |
RCV004762088 | SCV005369321 | uncertain significance | not provided | 2023-07-16 | 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 a control individual and not present in any individuals with breast cancer (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 15235021, 22850631, 33471991) |