Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000700425 | SCV000829179 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-10-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDH1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 860 of the CDH1 protein (p.Asp860His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |
| Ambry Genetics | RCV003163251 | SCV003867772 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.D860H variant (also known as c.2578G>C), located in coding exon 16 of the CDH1 gene, results from a G to C substitution at nucleotide position 2578. The aspartic acid at codon 860 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |