Table 2

NOTCH2 mutations: genomic and protein coordinates, protein predictions, and results of functional analysis

MutationExonProtein domainType of mutationOriginPredicted effect of mutationFunctional analysis
GenomicProteinMutPredSNPs&GoPolyphen2SIFT
c.1117T→Cp.Cys373Arg7EGF 9MissensePaternal0.873DamagingDamagingDamagingDamaging
c.1147C→Tp.Pro383Ser7EGF 10MissenseMaternal0.694DamagingDamagingDamagingDamaging
c.1180C→Tp.Pro394Ser7EGF 10MissenseUnknown0.611DamagingDamagingBenignNot tested
c.1331G→A*p.Cys444Tyr8EGF 11MissenseMaternal0.999DamagingDamagingDamagingDamaging
c.1438T→Cp.Cys480Arg9EGF 10MissenseUnknown0.99DamagingDamagingDamagingNot tested
c.2043T→Ap.Ile681Asn13EGF 17/18MissenseUnknown0.519DamagingDamagingBenignNot tested
c.2566_2567delAGp.Ser855fs16EGF 22FrameshiftMaternalN/AN/AN/AN/ANot tested
c.5857C→Tp.Arg1953Cys32ANK 4MissenseUnknown0.588DamagingDamagingDamagingDamaging
c.5858G→Ap.Arg1953His32ANK 4MissenseUnknown0.591BenignDamagingDamagingNot tested
c.6007C→Tp.Arg2003X33ANK 5Non-senseDe novoN/AN/AN/AN/ADamaging
c.5930-1G→A*N/A33ANK 5Splice site alterationMaternalN/AN/AN/AN/ADamaging
  • MutPred score, probability of deleterious or disease associated mutation. MutPred: Li B, Krishnan VG, Mort ME, Xin F, Kamati KK, Cooper DN, Mooney SD, Radivojac P. Automated inference of molecular mechanisms of disease from amino acid substitutions. Bioinformatics 2009;25:2744–50. http://mutpred.mutdb.org/

  • SNPs&Go: Calabrese R, Capriotti E, Fariselli P, Martelli PL, Casadio R. Functional annotations improve the predictive score of human disease-related mutations in proteins. Hum Mutat 2009;30:1237–44. http://snps-and-go.biocomp.unibo.it/snps-and-go/index.html

  • Polyphen: Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. Nat Methods 2010;7:248–9. http://genetics.bwh.harvard.edu/pph2/

  • SIFT: Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073–81. http://sift.jcvi.org/

  • * Previously reported mutations.

  • Both changes from patient 7.