All variants were filtered using a previously reported algorithm (Shanks et al., 2013 a ) and analysed using standard pathogenicity prediction programs including PolyPhen-2 (Adzhubei et al., 2010), SIFT (Kumar et al., 2009), MutPred (Li et al., 2009) and the mutation interpretation software Alamut (http://www.interactive-biosoftware.com/).com/
Guidelines for de novo mutation screening analysis, and more importantly, guidelines for mutation interpretation, will need to be elaborated as more and more laboratories will be offering exome or whole genome analysis for diagnostic purposes.
AL and ALB-D sequenced TP53 from the tumor panel described by Horlings et al [ 25] and helped with TP53 mutation interpretation, PN provided tumor information from the Joosse tumor panel [ 24].
ASSEDA, the successor software to ASSA, provides a new isoform-oriented type of mutation interpretation, updates the coordinate system to HG19 (GRCh37), adds current gene and single nucleotide polymorphism (SNP) annotations (dbSNP135), and provides additional ribls for other splicing regulatory sites (SRp55, TIA1, ELAVL1, hnRNP A1, hnRNP H, and PTB).
Polyphen2 and SIFT are two of a host of programs in use for mutation interpretation Here, we show that for missense variants in IRF6, Polyphen2 and SIFT predictions were not in perfect agreement.
Similarly, we hope that ReKINect, and similar tools, can be utilized to close the cancer mutation interpretation gap.
Candidate variants were evaluated using the mutation interpretation software Alamut version 2.2.1 or Alamut HT version 1.1.5 (Interactive Biosoftware, Rouen, France) and segregation analysis was performed for selected variants.
To support the interpretation of putative kinase domain mutations, we created a prototype mutation interpretation tool for tyrosine kinases (TKs), called "Mutagrator", located at http://cbio.mskcc.org/∼lash/mutagrator/ (freely available to the research community).
Variants of unknown significance (VUS) were evaluated using in silico mutation interpretation software – Alamut.
The Alamut Mutation Interpretation Software (Interactive Biosoftware, Rouen, France) predicted that rs11078928 would result in deletion of exon 6.
