Supplementary Materials

Supplementary Material for:

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease

Angharad M. Roberts, James S. Ware, Daniel S. Herman, Sebastian Schafer, John Baksi, Alexander G. Bick, Rachel J. Buchan, Roddy Walsh, Shibu John, Samuel Wilkinson, Francesco Mazzarotto, Leanne E. Felkin, Sungsam Gong, Jacqueline A. L. MacArthur, Fiona Cunningham, Jason Flannick, Stacey B. Gabriel, David M. Altshuler, Peter S. Macdonald, Matthias Heinig, Anne M. Keogh, Christopher S. Hayward, Nicholas R. Banner, Dudley J. Pennell, Declan P. O'Regan, Tan Ru San, Antonio de Marvao, Timothy J. W. Dawes, Ankur Gulati, Emma J. Birks, Magdi H. Yacoub, Michael Radke, Michael Gotthardt, James G. Wilson, Christopher J. O'Donnell, Sanjay K. Prasad, Paul J. R. Barton, Diane Fatkin, Norbert Hubner, Jonathan G. Seidman, Christine E. Seidman,* Stuart A. Cook*

*Corresponding author. E-mail: stuart.cook{at}nhcs.com.sg (S.A.C.); cseidman{at}genetics.med.harvard.edu (C.E.S.)

Published 14 January 2015, Sci. Transl. Med. 7, 270ra6 (2015)
DOI: 10.1126/scitranslmed.3010134

This PDF file includes:

  • Phenotype ascertainment methods for study cohorts
  • Fig. S1. Schematic representation of the unselected DCM cohort recruitment pathway and analyses.
  • Fig. S2. TTN sequencing coverage for each cohort.
  • Fig. S3. Sites susceptible to truncating events are non-uniformly distributed within the TTN gene but do not influence clustering effects in the A-band.
  • Fig. S4. Alternative splicing of TTN in the human heart.
  • Fig. S5. Time to events in FHS individuals grouped by TTNtv presence.
  • Fig. S6. Truncated transcript length is correlated with indices of cardiac impairment severity in DCM.
  • Fig. S7. FHS exam 7 CMR.
  • Fig. S8. FHS and JHS additional CMR and echocardiography exams.
  • Fig. S9. mRNA transcripts encoding truncated TTN proteins are expressed in human LV.
  • Table S1. TTNtv identified in UK prospective DCM cohort.
  • Table S2. TTNtv identified in the FHS offspring cohort.
  • Table S3. TTNtv identified in the JHS cohort.
  • Table S4. TTNtv identified in end-stage DCM.
  • Table S5. TTNtv identified in healthy volunteers.
  • Table S6. Titin reference transcript and protein identifiers.
  • Table S7. Overview of TTN transcripts and exon usage.
  • Table S8. TTNtv in publicly available control populations.
  • Table S9. Burden, type, and distribution of TTNtv in publicly available control populations.
  • Table S10. FHS exam 7 CMR phenotype grouped by TTNtv presence.
  • Table S11. Prevalence of DCM in FHS and JHS participants, grouped by TTNtv presence.
  • Table S12. Time to event empirical Cox proportional hazard models for the FHS cohort.
  • Table S13. TTNtv identified in replication cohorts.
  • Table S14. Linear modeling of the relationship between TTN genotype and phenotype for 14 continuous variables in the unselected DCM cohort.
  • Table S15. Full linear model describes impact of multivariate TTN genotype on phenotype for 14 continuous variables in the unselected DCM cohort.
  • Table S16. Linear models for FHS exam 7 CMR.
  • Table S17. Linear models for additional FHS and JHS exams.
  • Table S18. Allele-specific expression of exons containing TTNtv using RNA sequencing data.
  • References (6567)

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