Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000541565 | SCV000637748 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 595 of the CDH1 protein (p.Pro595Ser). This variant is present in population databases (rs755622441, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 463730). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV000570513 | SCV000666287 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.P595S variant (also known as c.1783C>T), located in coding exon 12 of the CDH1 gene, results from a C to T substitution at nucleotide position 1783. The proline at codon 595 is replaced by serine, an amino acid with similar properties. This variant was reported in 2/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). 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. |
| Color Diagnostics, |
RCV000570513 | SCV000689487 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-04 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 595 of the CDH1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/282892 chromosomes 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. |
| Center for Genomic Medicine, |
RCV002268148 | SCV002551783 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing |