Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001355667 | SCV001550617 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The APC c.1744-?_1958+?del variant (chr:5 g.112170648_112170862del GRCh37) results in a deletion of exon 14, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The c.1744-?_1958+?del variant was identified in 4 of 1282 proband chromosomes (frequency: 0.003) from Czech/Slovak, European, Polish and Belgian individuals or families with classical FAP (Stekrova 2007, Sieber 2002, Plawski 2008, Michils 2005). The c.1744-?_1958+?del variant was confirmed by long-range PCR in one study (Michilis 2005). The variant was also identified in ClinVar (classified as pathogenic by Mayo Clinic Genetic Testing Laboratories), Clinvitae (1x), and Zhejiang Colon Cancer Database (1x). The variant was not identified in dbSNP, Cosmic, UMD-LSDB, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project or the Exome Aggregation Consortium (August 8th 2016). The c.1744-?_1958+?del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 528 and leads to a premature stop codon 20 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in familial adenomatous polyposis and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |