Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573799 | SCV000669018 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-27 | criteria provided, single submitter | clinical testing | The p.E629Q variant (also known as c.1885G>C), located in coding exon 12 of the CDH1 gene, results from a G to C substitution at nucleotide position 1885. The glutamic acid at codon 629 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Labcorp Genetics |
RCV000689849 | SCV000817518 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-19 | 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 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"). ClinVar contains an entry for this variant (Variation ID: 483226). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 629 of the CDH1 protein (p.Glu629Gln). |