Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567113 | SCV000666275 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-12 | criteria provided, single submitter | clinical testing | The p.D860N variant (also known as c.2578G>A), located in coding exon 16 of the CDH1 gene, results from a G to A substitution at nucleotide position 2578. The aspartic acid at codon 860 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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. |
Labcorp Genetics |
RCV000700036 | SCV000828772 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 860 of the CDH1 protein (p.Asp860Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 36436516). ClinVar contains an entry for this variant (Variation ID: 481675). 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. 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. |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000700036 | SCV003926965 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2 (PMID: 30311375) |