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.82470G>A p.W27490Xnonsense 1VUS0.000000
3. c.56572C>T p.R18858Xnonsense 1VUS0.000027
4. c.60643_60644del p.Arg20215Glufs*13frameshift 1VUS0.000000
5. c.70563dup p.Glu23522Argfs*10frameshift 1VUS0.000000
6. c.35083G>T p.E11695Xnonsense 1VUS0.000000
7. c.85713G>A p.W28571Xnonsense 1VUS0.000000
8. c.46925_46928del p.Lys15642Metfs*10frameshift 1VUS0.000000
9. c.13900G>T p.E4634Xnonsense 1VUS0.000000
10. c.98504_98505del p.Arg32835Thrfs*5frameshift 1VUS0.000000
11. c.64453C>T p.R21485Xnonsense 1VUS0.000025
12. c.86229delinsAA p.Ile28744Asnfs*12frameshift 1VUS0.000000
13. c.62722C>T p.R20908Xnonsense 1VUS0.000000
14. c.100825C>T p.R33609Xnonsense 1VUS0.000000
15. c.75633_75636dup p.Val25213Cysfs*25frameshift 1VUS0.000000
16. c.63625C>T p.R21209Xnonsense 1VUS0.000000
17. c.16077del p.Phe5359Leufs*28frameshift 1VUS0.000000
18. c.51436C>T p.Q17146Xnonsense 1VUS0.000000
19. c.98506C>T p.R32836Xnonsense 1VUS0.000000
20. c.44272C>T p.R14758Xnonsense 1VUS0.000008
21. c.76865G>A p.W25622Xnonsense 1VUS0.000000
22. c.92652_92659del p.Asp30885Serfs*3frameshift 1VUS0.000000
23. c.85238del p.Thr28413Ilefs*3frameshift 1VUS0.000000
24. c.60163_60164del p.Ile20055Cysfs*7frameshift 1VUS0.000000
25. c.70200_70203dup p.Ile23402Aspfs*6frameshift 1VUS0.000000
26. c.31035T>G p.Y10345Xnonsense 1VUS0.000000
27. c.12742C>T p.Q4248Xnonsense 1VUS0.000000
28. c.98265_98268dup p.His32757Asnfs*4frameshift 1VUS0.000000
29. c.61495C>T p.R20499Xnonsense 1VUS0.000000
30. c.74104C>T p.Q24702Xnonsense 1VUS0.000000
31. c.46803G>A p.W15601Xnonsense 1VUS0.000000
32. c.85946del p.Val28649Glyfs*20frameshift 1VUS0.000000
33. c.60940del p.Thr20314Leufs*5frameshift 1VUS0.000000
34. c.99058del p.Glu33020Argfs*41frameshift 1VUS0.000000
35. c.14194C>T p.Q4732Xnonsense 1VUS0.000000
36. c.47314C>T p.R15772Xnonsense 1VUS0.000000
37. c.88727delC p.Thr29576LysfsTer36frameshift 1VUS0.000008
38. c.89787del p.Val29930Cysfs*36frameshift 1VUS0.000000
39. c.63025C>T p.R21009Xnonsense 1VUS0.000000
40. c.12358C>T p.Q4120Xnonsense 1VUS0.000008
41. c.76822del p.Leu25608*frameshift 1VUS0.000000
42. c.24019C>T p.R8007Xnonsense 1VUS0.000000
43. c.51444del p.Asp17149Ilefs*4frameshift 1VUS0.000000
44. c.67952_67955dup p.Lys22652Asnfs*4frameshift 1VUS0.000000

References

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.