Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820591 | SCV000961308 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2019-03-26 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 14-16 of the CDH1 gene. The 5' boundary is likely confined to intron 13. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. A gross deletion of exons 14-16 has been observed in a family affected with diffuse gastric cancer (PMID: 19168852). This variant is expected to delete the C-terminal portion of the cytoplasmic domain of the CDH1 (E-cadherin) protein, which includes the binding domains for the PIP5K1C (phosphatidylinositol phosphate kinase, type I gamma) and CTNNB1 (beta-catenin) proteins (PMID: 22850631). Loss of these domains is expected to disrupt normal E-cadherin function. This suggests that deletion of this region of the CDH1 protein is causative of disease. Sub-genic deletion of exon 16 and sub-genic deletion of exons 14-15 have been determined to be pathogenic (PMID: 19168852, Invitae). Therefore, deletions that fully encompass that region are also expected to be pathogenic. For these reasons, this variant has been classified as Pathogenic. |