Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000459309 | SCV000563995 | pathogenic | Lynch syndrome | 2016-09-04 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 5 of the EPCAM gene. This creates a premature translational stop signal and is expected to result in an absent or disrupted protein product. A simliar deletion of exon 5 has been reported as homozygous in an individual with congenital tufting enteropathy (PMID: 24142340). Gross deletions that result in the loss-of-function of the EPCAM protein are known to cause congenital tufting enteropathy. In contrast, deletions involving the 3' exons (at least exon 9) lead to transcriptional read-through from EPCAM into the adjacent MSH2 gene, resulting in hypermethylation of the MSH2 promoter and silencing of MSH2 expression, causing Lynch syndrome (PMID: 19098912, 19177550, 21309036). For these reasons, this variant has been classified as Pathogenic for congenital tufting enteropathy. However, this variant is not likely to confer risk for Lynch syndrome. |