TTN truncating variants in DCM cohorts

The table below lists the 45 rare (MAF<0.0001 in ExAC) truncating TTN variants identified in a cohort of 304 DCM patients. When this rare variant frequency of 0.14803 is compared with a background population rate of 0.00876, there is a statistically significant case excess of 0.13927 (p<0.0001), which suggests that approximately 42 of these variants may be pathogenic.

Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM

No. Variant (CDS) Variant (Protein) Variant Type Cases (304)OMGL class ExAC frequency
1. c.97417del p.Arg32473Valfs*19frameshift 2VUS0.000000
2. c.13900G>T p.E4634Xnonsense 1VUS0.000000
3. c.46925_46928del p.Lys15642Metfs*10frameshift 1VUS0.000000
4. c.98504_98505del p.Arg32835Thrfs*5frameshift 1VUS0.000000
5. c.64453C>T p.R21485Xnonsense 1VUS0.000025
6. c.75633_75636dup p.Val25213Cysfs*25frameshift 1VUS0.000000
7. c.86229delinsAA p.Ile28744Asnfs*12frameshift 1VUS0.000000
8. c.62722C>T p.R20908Xnonsense 1VUS0.000000
9. c.100825C>T p.R33609Xnonsense 1VUS0.000000
10. c.63625C>T p.R21209Xnonsense 1VUS0.000000
11. c.16077del p.Phe5359Leufs*28frameshift 1VUS0.000000
12. c.51436C>T p.Q17146Xnonsense 1VUS0.000000
13. c.98506C>T p.R32836Xnonsense 1VUS0.000000
14. c.92652_92659del p.Asp30885Serfs*3frameshift 1VUS0.000000
15. c.44272C>T p.R14758Xnonsense 1VUS0.000008
16. c.76865G>A p.W25622Xnonsense 1VUS0.000000
17. c.31035T>G p.Y10345Xnonsense 1VUS0.000000
18. c.85238del p.Thr28413Ilefs*3frameshift 1VUS0.000000
19. c.60163_60164del p.Ile20055Cysfs*7frameshift 1VUS0.000000
20. c.70200_70203dup p.Ile23402Aspfs*6frameshift 1VUS0.000000
21. c.12742C>T p.Q4248Xnonsense 1VUS0.000000
22. c.98265_98268dup p.His32757Asnfs*4frameshift 1VUS0.000000
23. c.61495C>T p.R20499Xnonsense 1VUS0.000000
24. c.60940del p.Thr20314Leufs*5frameshift 1VUS0.000000
25. c.99058del p.Glu33020Argfs*41frameshift 1VUS0.000000
26. c.74104C>T p.Q24702Xnonsense 1VUS0.000000
27. c.46803G>A p.W15601Xnonsense 1VUS0.000000
28. c.85946del p.Val28649Glyfs*20frameshift 1VUS0.000000
29. c.47314C>T p.R15772Xnonsense 1VUS0.000000
30. c.14194C>T p.Q4732Xnonsense 1VUS0.000000
31. c.88727delC p.Thr29576LysfsTer36frameshift 1VUS0.000008
32. c.89787del p.Val29930Cysfs*36frameshift 1VUS0.000000
33. c.63025C>T p.R21009Xnonsense 1VUS0.000000
34. c.12358C>T p.Q4120Xnonsense 1VUS0.000008
35. c.76822del p.Leu25608*frameshift 1VUS0.000000
36. c.67952_67955dup p.Lys22652Asnfs*4frameshift 1VUS0.000000
37. c.24019C>T p.R8007Xnonsense 1VUS0.000000
38. c.51444del p.Asp17149Ilefs*4frameshift 1VUS0.000000
39. c.56572C>T p.R18858Xnonsense 1VUS0.000027
40. c.82470G>A p.W27490Xnonsense 1VUS0.000000
41. c.85713G>A p.W28571Xnonsense 1VUS0.000000
42. c.60643_60644del p.Arg20215Glufs*13frameshift 1VUS0.000000
43. c.70563dup p.Glu23522Argfs*10frameshift 1VUS0.000000
44. c.35083G>T p.E11695Xnonsense 1VUS0.000000


1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.