Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709395 | SCV000839083 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001019414 | SCV001180769 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | The p.F317L variant (also known as c.949T>C), located in coding exon 7 of the CDH1 gene, results from a T to C substitution at nucleotide position 949. The phenylalanine at codon 317 is replaced by leucine, an amino acid with highly similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000709395 | SCV001511196 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-07-16 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 584915). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 317 of the CDH1 protein (p.Phe317Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. |