Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825333 | SCV000966628 | uncertain significance | not specified | 2018-10-24 | criteria provided, single submitter | clinical testing | The p.Thr17Met variant in EPCAM has not been previously reported in affected ind ividuals. This variant has been reported as a variant of uncertain significance in ClinVar (Variation ID# 188106) and has been identified in 0.007% (1/14976) of European chromosomes by the gnomAD (http://gnomad.broadinstitute.org). Computat ional prediction tools and conservation analysis suggest that the p.Thr17Met var iant may not impact the protein, though this information is not predictive enoug h to rule out pathogenicity. In summary, this variant is unlikely to be causativ e for autosomal dominant Lynch syndrome which is due to loss of the translation termination signal but it is uncertain significance for autosomal recessive cong enital tufting enteropathy which can be caused by missense and loss of function variants. ACMG/AMP Criteria applied: PM2, BP4. |
| Labcorp Genetics |
RCV001850372 | SCV002183166 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with methionine at codon 17 of the EPCAM protein (p.Thr17Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with EPCAM-related conditions. 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. |
| St. |
RCV003325193 | SCV004031132 | uncertain significance | Lynch syndrome 8 | 2023-08-17 | criteria provided, single submitter | clinical testing | The EPCAM c.50C>T (p.Thr17Met) missense variant has a maximum subpopulation frequency of 0.003% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with EPCAM-related disease. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |