Table 1.

Summary of bioinformatic analyses of the detected novel sequence variants

Novel variantResidue changeProtein domainMAFaConservationHuman Splicing Finder 3.0Grantham difference scorePolyPhen scoreSIFT scoreMutation taster prediction
c.293T>Gp.(Leu98Arg)transmembrane (helical)0 (not reported) 0.3%bhighly conserved, within conserved regionmutation in early exonic positions potentially breaking ESE site1021.0 probably damaging0 damagingdisease causing
c.929C>Tp.(Pro310Leu)kinase (ABC1 subdomain)0 (not reported)highly conservedmutation in late exonic positions potentially breaking ESE site981.0 probably damaging0 damagingdisease causing
c.1493_1494CC>AAp.(Ala498Glu)0 (not reported)low conservationpotential creation of exonic ESE site930.173 benign0 damagingdisease causing
c.1339dupGp.(Glu447Glyfs10)<1:10,000 0.3%bhighly conservedpotential activation of exonic cryptic acceptor site, or alteration of exonic ESE site, or creation of exonic ESS siteNANANAdisease causing
  • ESE, exonic splicing enhancer; ESS, exonic splicing silencer; NA, not applicable.

  • a MAF, minor allele frequency; estimation based on data of 2577 individual genomes cataloged by the 1000 Genomes Project; 6503 samples collected at NHLBI Exome Sequencing Project and data from 60,706 individuals aggregated by the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org); (accessed January 31, 2015).

  • b In-house allele frequency database representative for Turkish population (collection of 373 individual genomes; accessed October 22, 2014).