Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001219823 | SCV001391781 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-02-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CDH1-related conditions. This sequence change replaces leucine with proline at codon 276 of the CDH1 protein (p.Leu276Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. |
| Ambry Genetics | RCV003163693 | SCV003867725 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.L276P variant (also known as c.827T>C), located in coding exon 6 of the CDH1 gene, results from a T to C substitution at nucleotide position 827. The leucine at codon 276 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. 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. |