Pathogenic Analysis of R۴۱۴C Mutation in the APC Gene in FAP Cancer

Background: Familial adenomatous polyposis is one of the colon cancer syndromes with theautosomal dominant disorder. Patients with this syndrome suffer from multiple polyps, mainly inthe colorectal area, which, at an average age of ۳۵ to ۴۰ years, have an almost inevitableprogression to colon cancer. These patients mainly have a mutation (Germline) in the gene(Adenomatous polyposis coli, APC) on chromosome ۵q۲۱. The main mutation in patients withthis disease is missense. In this effect, a single nucleotide polymorphism (SNP) in NCBI wasselected as a missense mutation in the APC gene for investigation.Materials and Methods: In (rs۱۳۷۸۵۴۵۶۷ C> T), the effect of conversion of arginine (acidicand hydrophilic amino acid) to cysteine (polar amino acid and hydrophobicity) on codon ۴۱۴ onprotein structure was investigated using bioinformatics sites SIFT, PROVEAN, POLYPHEN.Results: In the SIFT database, Amino acids with probabilities LESS THAN ۰.۰۵ are predicted tobe deleterious. in this STUDY, Substitution at pos ۴۱۴ from R to C is predicted to AFFECTPROTEIN FUNCTION with a score of ۰.۰۰. Also in the PROVEAN database, Variants with ascore equal to or below -۲.۵ are considered "deleterious, PROVEAN predicts R۴۱۴C variantDELETERIOUS with SCORE = -۷.۹۱۶. Also, POLYPHEN-۲ showed this mutation is predictedto be PROBABLY DAMAGING with a score of ۱.۰۰۰ (sensitivity: ۰.۰۰; specificity: ۱.۰۰).Conclusion: The R۴۱۴C variant of the APC gene is likely to be a potentially pathogenic SNP.However, further investigation is needed to clarify this issue.