TTN non-truncating variants in DCM cohorts


The table below lists the 70 rare (MAF<0.0001 in ExAC) non-truncating TTN variants identified in a cohort of 156 DCM patients. When this rare variant frequency of 0.44870 is compared with a background population rate of 0.39200, there is a statistically significant case excess of 0.05670 (p<0.0001), which suggests that approximately of these variants may be pathogenic.


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



No. Variant (CDS) Variant (Protein) Variant Type Cases (156)LMM class ExAC frequency
1. c.5132C>T p.S1711Fmissense 1VUS0.000016
2. c.54167G>A p.R18056Qmissense 1VUS0.000026
3. c.102428T>C p.M34143Tmissense 1VUS0.000074
4. c.93968C>T p.A31323Vmissense 1VUS0.000057
5. c.62780G>A p.R20927Hmissense 1VUS0.000008
6. c.99434G>A p.R33145Qmissense 1VUS0.000033
7. c.6478A>G p.T2160Amissense 1VUS0.000016
8. c.20260A>G p.Lys6754Glumissense 1VUS0.000000
9. c.11450G>A p.G3817Dmissense 1VUS0.000017
10. c.43019T>C p.I14340Tmissense 1VUS0.000008
11. c.3469G>A p.V1157Imissense 1VUS0.000041
12. c.80608C>A p.Pro26870Thrmissense 1VUS0.000000
13. c.89947G>A p.V29983Mmissense 1VUS0.000099
14. c.48395G>A p.R16132Hmissense 1VUS0.000066
15. c.5582G>A p.R1861Hmissense 1VUS0.000082
16. c.96140C>T p.T32047Mmissense 1VUS0.000057
17. c.58982G>A p.G19661Dmissense 1VUS0.000016
18. c.55139T>C p.I18380Tmissense 1VUS0.000050
19. c.9674A>G p.N3225Smissense 1VUS0.000024
20. c.68272G>A p.D22758Nmissense 1VUS0.000026
21. c.78980G>A p.R26327Qmissense 1VUS0.000049
22. c.74527A>G p.N24843Dmissense 1VUS0.000033
23. c.1186G>A p.A396Tmissense 1VUS0.000008
24. c.50647C>T p.Pro16883Sermissense 1VUS0.000000
25. c.39163A>G p.Lys13055Glumissense 1VUS0.000000
26. c.91478A>G p.Glu30493Glymissense 1VUS0.000000
27. c.58684A>G p.Ile19562Valmissense 1VUS0.000000
28. c.105590G>A p.G35197Dmissense 1VUS0.000041
29. c.94629A>G p.I31543Mmissense 1VUS0.000066
30. c.63632T>C p.Val21211Alamissense 1VUS0.000000
31. c.99814C>T p.L33272Fmissense 1VUS0.000009
32. c.12037G>A p.Ala4013Thrmissense 1VUS0.000000
33. c.6941T>C p.I2314Tmissense 1VUS0.000008
34. c.18663A>C p.E6221Dmissense 1VUS0.000099
35. c.20742T>A p.Phe6914Leumissense 1VUS0.000000
36. c.28754A>C p.Glu9585Alamissense 1VUS0.000000
37. c.70181C>T p.T23394Mmissense 1VUS0.000024
38. c.77816A>C p.Asp25939Alamissense 1VUS0.000000
39. c.22386T>G p.Asp7462Glumissense 1VUS0.000000
40. c.72985A>G p.Asn24329Aspmissense 1VUS0.000000
41. c.85195G>A p.E28399Kmissense 1VUS0.000016
42. c.37432C>T p.P12478Smissense 2VUS0.000000
43. c.93472G>C p.Asp31158Hismissense 1VUS0.000000
44. c.62290G>C p.Glu20764Glnmissense 1VUS0.000000
45. c.89766G>C p.Lys29922Asnmissense 1VUS0.000000
46. c.57415A>C p.Ile19139Leumissense 1VUS0.000000
47. c.96286G>A p.A32096Tmissense 1VUS0.000066
48. c.54091A>G p.S18031Gmissense 1VUS0.000008
49. c.64903C>T p.R21635Cmissense 1VUS0.000024
50. c.107285G>A p.R35762Qmissense 1VUS0.000033
51. c.6029A>G p.Y2010Cmissense 1VUS0.000008
52. c.11140A>G p.Ile3714Valmissense 1VUS0.000000
53. c.72488G>A p.R24163Hmissense 1VUS0.000054
54. c.26765G>A p.Arg8922Glnmissense 1VUS0.000000
55. c.19015T>C p.Tyr6339Hismissense 1VUS0.000000
56. c.24344G>A p.S8115Nmissense 1VUS0.000083
57. c.2605A>T p.T869Smissense 1VUS0.000041
58. c.84523T>C p.Trp28175Argmissense 1VUS0.000000
59. c.98296G>T p.D32766Ymissense 1VUS0.000008
60. c.47887A>G p.M15963Vmissense 1VUS0.000033
61. c.58705G>A p.D19569Nmissense 1VUS0.000017
62. c.105630A>C p.Gln35210Hismissense 1VUS0.000000
63. c.98243G>A p.R32748Hmissense 1VUS0.000066
64. c.54685G>A p.V18229Mmissense 1VUS0.000091
65. c.102638A>G p.N34213Smissense 1VUS0.000008
66. c.67147G>A p.G22383Rmissense 1VUS0.000058
67. c.25046C>G p.A8349Gmissense 1VUS0.000008
68. c.39749_39766delTTGCTCCTGAAGAGGAAA inframe 1VUS0.000000
69. c.15369_15371delGTT inframe 1VUS - favor pathogenic0.000000

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.