Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001048530 | SCV001212541 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 807 of the CDH1 protein (p.Ile807Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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 has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (ExAC no frequency). |
| Gene |
RCV001593218 | SCV001824099 | uncertain significance | not provided | 2020-08-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with a personal history of breast cancer (Momozawa 2018); This variant is associated with the following publications: (PMID: 30287823) |
| Ambry Genetics | RCV002451197 | SCV002737389 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-11 | criteria provided, single submitter | clinical testing | The p.I807T variant (also known as c.2420T>C), located in coding exon 15 of the CDH1 gene, results from a T to C substitution at nucleotide position 2420. This alteration was observed in 1/7,051 unselected female breast cancer patients and 1/11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). The isoleucine at codon 807 is replaced by threonine, an amino acid with similar properties. 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. |