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.37432C>T p.P12478Smissense 2VUS0.000000
2. c.11450G>A p.G3817Dmissense 1VUS0.000017
3. c.20742T>A p.Phe6914Leumissense 1VUS0.000000
4. c.99434G>A p.R33145Qmissense 1VUS0.000033
5. c.18663A>C p.E6221Dmissense 1VUS0.000099
6. c.102428T>C p.M34143Tmissense 1VUS0.000074
7. c.93968C>T p.A31323Vmissense 1VUS0.000057
8. c.22386T>G p.Asp7462Glumissense 1VUS0.000000
9. c.28754A>C p.Glu9585Alamissense 1VUS0.000000
10. c.57415A>C p.Ile19139Leumissense 1VUS0.000000
11. c.54091A>G p.S18031Gmissense 1VUS0.000008
12. c.62290G>C p.Glu20764Glnmissense 1VUS0.000000
13. c.5132C>T p.S1711Fmissense 1VUS0.000016
14. c.64903C>T p.R21635Cmissense 1VUS0.000024
15. c.80608C>A p.Pro26870Thrmissense 1VUS0.000000
16. c.9674A>G p.N3225Smissense 1VUS0.000024
17. c.89947G>A p.V29983Mmissense 1VUS0.000099
18. c.96140C>T p.T32047Mmissense 1VUS0.000057
19. c.26765G>A p.Arg8922Glnmissense 1VUS0.000000
20. c.19015T>C p.Tyr6339Hismissense 1VUS0.000000
21. c.24344G>A p.S8115Nmissense 1VUS0.000083
22. c.39749_39766delTTGCTCCTGAAGAGGAAA inframe 1VUS0.000000
23. c.47887A>G p.M15963Vmissense 1VUS0.000033
24. c.3469G>A p.V1157Imissense 1VUS0.000041
25. c.68272G>A p.D22758Nmissense 1VUS0.000026
26. c.54685G>A p.V18229Mmissense 1VUS0.000091
27. c.5582G>A p.R1861Hmissense 1VUS0.000082
28. c.58705G>A p.D19569Nmissense 1VUS0.000017
29. c.12037G>A p.Ala4013Thrmissense 1VUS0.000000
30. c.78980G>A p.R26327Qmissense 1VUS0.000049
31. c.6941T>C p.I2314Tmissense 1VUS0.000008
32. c.74527A>G p.N24843Dmissense 1VUS0.000033
33. c.91478A>G p.Glu30493Glymissense 1VUS0.000000
34. c.94629A>G p.I31543Mmissense 1VUS0.000066
35. c.99814C>T p.L33272Fmissense 1VUS0.000009
36. c.105590G>A p.G35197Dmissense 1VUS0.000041
37. c.25046C>G p.A8349Gmissense 1VUS0.000008
38. c.15369_15371delGTT inframe 1VUS - favor pathogenic0.000000
39. c.1186G>A p.A396Tmissense 1VUS0.000008
40. c.62780G>A p.R20927Hmissense 1VUS0.000008
41. c.54167G>A p.R18056Qmissense 1VUS0.000026
42. c.77816A>C p.Asp25939Alamissense 1VUS0.000000
43. c.6029A>G p.Y2010Cmissense 1VUS0.000008
44. c.72985A>G p.Asn24329Aspmissense 1VUS0.000000
45. c.70181C>T p.T23394Mmissense 1VUS0.000024
46. c.11140A>G p.Ile3714Valmissense 1VUS0.000000
47. c.85195G>A p.E28399Kmissense 1VUS0.000016
48. c.89766G>C p.Lys29922Asnmissense 1VUS0.000000
49. c.96286G>A p.A32096Tmissense 1VUS0.000066
50. c.93472G>C p.Asp31158Hismissense 1VUS0.000000
51. c.20260A>G p.Lys6754Glumissense 1VUS0.000000
52. c.107285G>A p.R35762Qmissense 1VUS0.000033
53. c.43019T>C p.I14340Tmissense 1VUS0.000008
54. c.48395G>A p.R16132Hmissense 1VUS0.000066
55. c.58982G>A p.G19661Dmissense 1VUS0.000016
56. c.55139T>C p.I18380Tmissense 1VUS0.000050
57. c.72488G>A p.R24163Hmissense 1VUS0.000054
58. c.84523T>C p.Trp28175Argmissense 1VUS0.000000
59. c.98296G>T p.D32766Ymissense 1VUS0.000008
60. c.98243G>A p.R32748Hmissense 1VUS0.000066
61. c.102638A>G p.N34213Smissense 1VUS0.000008
62. c.105630A>C p.Gln35210Hismissense 1VUS0.000000
63. c.2605A>T p.T869Smissense 1VUS0.000041
64. c.50647C>T p.Pro16883Sermissense 1VUS0.000000
65. c.39163A>G p.Lys13055Glumissense 1VUS0.000000
66. c.63632T>C p.Val21211Alamissense 1VUS0.000000
67. c.58684A>G p.Ile19562Valmissense 1VUS0.000000
68. c.67147G>A p.G22383Rmissense 1VUS0.000058
69. c.6478A>G p.T2160Amissense 1VUS0.000016

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.