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

Nat Protoc 2009 25;4(7):1073-81. Epub 2009 Jun 25.

Department of Genomic Medicine, J. Craig Venter Institute, San Diego, California, USA.

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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http://dx.doi.org/10.1038/nprot.2009.86DOI Listing
November 2009
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References

(Supplied by CrossRef)

M Krawczak et al.
Hum. Mutat. 2000

S Henikoff et al.
Annu. Rev. Plant. Biol. 2003

PC Ng et al.
Genome Res. 2001

D Tchernitchko et al.
Clin. Chem. 2004

PC Ng et al.
Genome Res. 2002

SF Altschul et al.
Nucleic Acids Res. 1997

PC Ng et al.
Nucleic Acids Res. 2003

CT Saunders et al.
J. Mol. Biol. 2002

M Cargill et al.
Nat. Genet. 1999

JS Palmer et al.
Am. J. Hum. Genet. 2000

PC Ng et al.
Annu. Rev. Genom. 2006

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