Sorting Intolerant From Tolerant.
The functional relevance of these variants was assessed by the in silico prediction tools PolyPhen-2, Sorting Intolerant from Tolerant (SIFT), and Loss-Of-Function Transcript Effect Estimator (LOFTEE).
Using in silico models, namely PolyPhen-2 (Polymorphism Phenotyping v2), SIFT (Sorting Intolerant From Tolerant), and LOFTEE (Loss-Of-Function Transcript Effect Estimator), ExAC estimates the impact of a given variant on protein function.
All synonymous SNPs were characterized by SIFT (Sorting Intolerant From Tolerant) and determined to be tolerated.
Sorting Intolerant From Tolerant (SIFT) was first published in 2003 by Ng and Heinikoff from work done at the Fred Hutchinson Cancer Research Center in Seattle [14].
SIFT (Sorting Intolerant from Tolerant, http://sift.jcvi.org/www/SIFT_seq_submit2.html) was used to predict the impact of the mutation on the protein.
Further evaluation of detected nucleotide mutations consisted of Sorting Intolerant From Tolerant (SIFT; blocks.fhcrc.org/sift/SIFT.html) and screening against known databases: NCBI, Cosmic, UniProtKB/Swiss-Prot and JSNP (www.ncbi.nlm.nih.gov/SNP, www.sanger.ac.uk/genetics/CGP/cosmic/, ca.expasy.org/sprot/, snp.ims.u-tokyo.ac.jp/).
The SIFT (Sorting Intolerant from Tolerant) algorithm [3], is arguably the most commonly used tool for detecting deleterious amino acid substitutions due to its easy application towards large numbers of mutations.
Here we present a modified version of the SIFT (Sorting Intolerant from Tolerant) algorithm that utilizes protein sequence alignments with homologous sequences to identify functional mutations based on evolutionary fitness.
Based on multiple sequence alignment analysis, Grantham score (GMS = 112) and the SIFT (Sorting Intolerant From Tolerant [30]) prediction programme, the C315S missense mutation is not likely to affect protein function.
Substitution tolerance was estimated using the SIFT algorithm (Sorting Intolerant From Tolerant).
