Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000527755 | SCV000637684 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2017-08-07 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 12-13 of the CDH1 gene. It preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals with CDH1-related disease. This deletion removes 152 amino acid residues of the CDH1 protein (E-cadherin), including a portion of the extracellular domain and most of the transmembrane domain (PMID: 22850631). Although functional studies have not been done for this particular variant, loss of these residues will likely impair CDH1 function (PMID: 22850631, 19268662, 25388006). Also, a missense substitution in this region (p.Ala634Val) has been determined to be likely pathogenic and has been reported in multiple individuals affected with diffuse gastric cancer (PMID: 12588804, 15288293, 15735979, 17545690, 17221870, 24493355, Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |