Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985656 | SCV001134063 | uncertain significance | not provided | 2019-07-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002549651 | SCV003247774 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-03-19 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 801139). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 551 of the CDH1 protein (p.Glu551Gln). |
Ambry Genetics | RCV003169525 | SCV003913316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-13 | criteria provided, single submitter | clinical testing | The p.E551Q variant (also known as c.1651G>C), located in coding exon 11 of the CDH1 gene, results from a G to C substitution at nucleotide position 1651. The glutamic acid at codon 551 is replaced by glutamine, an amino acid with highly similar properties. This alteration was identified in a Chinese cohort of individuals with hereditary diffuse gastric cancer (HDGC) (Pan Z et al. J Cancer Res Clin Oncol, 2022 Aug;148:2145-2151). 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. |