Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000154615 | SCV000204288 | likely pathogenic | Familial multiple polyposis syndrome | 2011-03-29 | criteria provided, single submitter | clinical testing | The Ser1419fsx54 variant has not been previously reported in the literature or b een identified by our laboratory. However, an adjacent nucleotide variant, 4256d elG, resulting in a similar amino acid change, Ser1419fsX54, was identified in t umor tissue from an individual with colorectal carcinoma but not FAP (Lovig 2002 ; COSMIC). The Ser1419fsx54 variant is predicted to cause a frameshift, which al ters the protein's amino acid sequence beginning at codon 1419 and leads to a pr emature stop codon 54 amino acids downstream. From this DNA sequencing test, we cannot determine the effect this nucleotide change will have on the protein prod uced. It is possible that a truncated protein is generated. Alternatively, no pr otein would be produced from this allele if nonsense-mediated decay occurs, as p remature stop codons frequently result in degradation of the mRNA. Frameshift va riants in APC are commonly observed to be pathogenic, and loss of function of AP C is an established mechanism of disease in FAP (Human Mutation Gene Database, H GMD). Therefore, this variant is likely to be pathogenic. |