Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001297336 | SCV001486344 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2020-10-16 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 403 of the CDH1 protein (p.Ala403Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. |
| Ambry Genetics | RCV002350527 | SCV002647485 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-28 | criteria provided, single submitter | clinical testing | The p.A403S variant (also known as c.1207G>T), located in coding exon 9 of the CDH1 gene, results from a G to T substitution at nucleotide position 1207. The alanine at codon 403 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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. |
| Color Diagnostics, |
RCV002350527 | SCV004360474 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 403 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |