ClinVar Miner

Submissions for variant NM_002354.2(EPCAM):c.556-14A>G (rs376155665)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763487 SCV000894273 pathogenic Diarrhea 5, with tufting enteropathy, congenital; Hereditary nonpolyposis colorectal cancer type 8 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000144936 SCV000579404 pathogenic Diarrhea 5, with tufting enteropathy, congenital 2016-10-10 criteria provided, single submitter research
Invitae RCV000230671 SCV000287358 pathogenic Hereditary nonpolyposis colon cancer 2018-09-05 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the EPCAM mRNA. It has been shown to affect mRNA splicing through the creation of new splice acceptor site, which causes a frameshift at codon 186 and creates a premature translational stop signal (p.Tyr186Phefs*6) (PMID: 23462293, 24142340). It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs376155665, ExAC 0.01%). This variant has been reported in multiple individuals affected with congenital tufting enteropathy (CTE) (PMID: 23462293, 24142340, 28701297). ClinVar contains an entry for this variant (Variation ID: 157603). In cDNA sequence analysis using patient-derived RNA, this variant resulted in a frameshift caused by abnormal splicing (PMID: 24142340). An experimental study using cells expressing the truncated protein (p.Tyr186Phefs*6) has shown that this truncated protein lacks the transmembrane domain of EPCAM, resulting in loss of cell-surface EPCAM protein, and reduced protein secretion in vitro (PMID: 23462293). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000144936 SCV000191953 pathogenic Diarrhea 5, with tufting enteropathy, congenital 2013-07-01 no assertion criteria provided literature only

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