Skip to main content

Table 4 Examples of in silico algorithms

From: Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers

ToolsWebsiteDescription
PolyPhen-2http://genetics.bwh.harvard.edu/pph2/Predicts possible impact of an amino acid substitution on the structure and function of a human protein using straightforward physical and comparative considerations.
Proveanhttp://provean.jcvi.org/seq_submit.phpPredicts whether an amino acid substitution or “indel” has an impact on the biological function of a protein.
Sifthttps://sift.bii.a-star.edu.sg/www/SIFT_seq_submit2.htmlPredicts whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids.
Mutation tasterhttp://www.mutationtaster.org/Predicts the functional consequences of amino acid substitutions, intronic and synonymous alterations, short “indel” mutations and variant spanning intron-exon borders.
Mutation assessorhttp://mutationassessor.org/r3/Predicts the functional impact of amino-acid substitutions in proteins, such as mutations discovered in cancer or missense polymorphisms. The functional impact is assessed based on evolutionary conservation of the affected amino acid in protein homologs.
FATHMMhttp://fathmm.biocompute.org.uk/High-throughput web-server capable of predicting the functional consequences of both coding variants, i.e., non-synonymous single nucleotide variants (nsSNVs), and non-coding variants through Hidden Markov Models.
Align-GVGDhttp://agvgd.hci.utah.edu/agvgd_input.phpFreely available, web-based program that combines the biophysical characteristics of amino acids and protein multiple sequence alignments to predict where missense substitutions in genes of interest fall in a spectrum from enriched deleterious to enriched neutral.
Human splicing finderhttp://www.umd.be/HSF3/HSF.shtmlPredicts the effects of mutations on splicing signals and identifies splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction to identify exonic and intronic motifs.
  1. “indel” = insertion and/or deletion. Database and algorithm descriptions were taken from respective websites.