Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002618258 | SCV002960060 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-04-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 634 of the CDH1 protein (p.Ala634Glu). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV003289559 | SCV004008260 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-09 | criteria provided, single submitter | clinical testing | The p.A634E variant (also known as c.1901C>A), located in coding exon 12 of the CDH1 gene, results from a C to A substitution at nucleotide position 1901. The alanine at codon 634 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is 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. |