Investigating the Prediction of the Pathogenicityof p.Arg۶۶۱Trp Missense Mutation (rs۱۳۷۸۵۳۲۹۴)in the RB۱ Gene in Retinoblastoma with a BioinformaticsApproach

Background: Retinoblastoma is a rare type of cancer that developsrapidly when immature retinal cells transform. It is themost common primary malignant intraocular cancer in childrenunder ۵ years of age. Approximately half of the children withretinoblastoma have a congenital mutation on chromosome ۱۳;the RB۱ gene is located at ۱۳q۱۴. The Rb protein encoded by the RB۱ gene has a negative regulatory effect on the cell cycle due tothe inactivation of the transcription factor E۲F (the active and hypophosphorylatedform of the Rb protein binds to E۲F۱ and inactivatesit). Therefore, the transcription of genes that are necessaryfor the S phase is suppressed. The variant analyzed in this studywith bioinformatics tools is due to the replacement of argininewith tryptophan at position ۶۶۱ (p.Arg۶۶۱Trp; rs۱۳۷۸۵۳۲۹۴).The reason for this mentioned replacement is the change of cytosineto thymine in nucleotide ۱۹۸۱ in the gene (۱۹۸۱C>T).Materials and Methods: This mutation is predicted to bepathogenic with the score of ۱.۰۰۰ by PolyPhen۲, ۰.۷۳۹ byPANTHER, ۰.۹۱۹ by Phd-SNP, ۰.۰۰۰ by SIFT, ۰.۷۹۵ by SNAP,۰.۸۳۴ by Meta-SNP, ۱۳ by Varsome, ۸۷% by PredictSNP and۷۷% by MAPP. (If >۰.۰۵ mutation is predicted neutral by SIFTand if >۰.۵ mutations are predicted pathogenic by PANTHER,PhD-SNP, SNAP and Meta-SNP).Results: Based on these scores and analysis, it is predicted thatthis variant of the RB۱ gene (rs۱۳۷۸۵۳۲۹۴) is pathogenic andcauses disease. This prediction is very likely to be confirmed byscientific and laboratory tests because the pathogenicity scoresof this SNP are very high.Conclusion: According to our results, rs۱۳۷۸۵۳۲۹۴ might havepathogenic effects on the Rb protein. This theory should beproved with experimental studies because the score of pathogenicityof this SNP is very high.