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      Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.

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          Abstract

          The effect of genetic mutation on phenotype is of significant interest in genetics. The type of genetic mutation that causes a single amino acid substitution (AAS) in a protein sequence is called a non-synonymous single nucleotide polymorphism (nsSNP). An nsSNP could potentially affect the function of the protein, subsequently altering the carrier's phenotype. This protocol describes the use of the 'Sorting Tolerant From Intolerant' (SIFT) algorithm in predicting whether an AAS affects protein function. To assess the effect of a substitution, SIFT assumes that important positions in a protein sequence have been conserved throughout evolution and therefore substitutions at these positions may affect protein function. Thus, by using sequence homology, SIFT predicts the effects of all possible substitutions at each position in the protein sequence. The protocol typically takes 5-20 min, depending on the input. SIFT is available as an online tool (http://sift.jcvi.org).

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          Author and article information

          Journal
          Nat Protoc
          Nature protocols
          Springer Science and Business Media LLC
          1750-2799
          1750-2799
          2009
          : 4
          : 7
          Affiliations
          [1 ] Department of Genomic Medicine, J. Craig Venter Institute, San Diego, California, USA.
          Article
          nprot.2009.86
          10.1038/nprot.2009.86
          19561590
          887890cc-b38b-4d23-b706-2a9918be8a6f
          History

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