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 (304 patients from OMGL, 156 patients from LMM). 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)OMGL classLMM class ExAC frequency
1. c.37432C>T p.P12478Smissense 2VUS (2)0.000000
2. c.3469G>A p.V1157Imissense 1VUS (1)0.000041
3. c.80608C>A p.Pro26870Thrmissense 1VUS (1)0.000000
4. c.89947G>A p.V29983Mmissense 1VUS (1)0.000099
5. c.6029A>G p.Y2010Cmissense 1VUS (1)0.000008
6. c.96140C>T p.T32047Mmissense 1VUS (1)0.000057
7. c.5582G>A p.R1861Hmissense 1VUS (1)0.000082
8. c.11140A>G p.Ile3714Valmissense 1VUS (1)0.000000
9. c.26765G>A p.Arg8922Glnmissense 1VUS (1)0.000000
10. c.19015T>C p.Tyr6339Hismissense 1VUS (1)0.000000
11. c.24344G>A p.S8115Nmissense 1VUS (1)0.000083
12. c.39749_39766delTTGCTCCTGAAGAGGAAA inframe 1VUS (1)0.000000
13. c.47887A>G p.M15963Vmissense 1VUS (1)0.000033
14. c.68272G>A p.D22758Nmissense 1VUS (1)0.000026
15. c.54685G>A p.V18229Mmissense 1VUS (1)0.000091
16. c.58705G>A p.D19569Nmissense 1VUS (1)0.000017
17. c.74527A>G p.N24843Dmissense 1VUS (1)0.000033
18. c.1186G>A p.A396Tmissense 1VUS (1)0.000008
19. c.78980G>A p.R26327Qmissense 1VUS (1)0.000049
20. c.91478A>G p.Glu30493Glymissense 1VUS (1)0.000000
21. c.94629A>G p.I31543Mmissense 1VUS (1)0.000066
22. c.99814C>T p.L33272Fmissense 1VUS (1)0.000009
23. c.105590G>A p.G35197Dmissense 1VUS (1)0.000041
24. c.25046C>G p.A8349Gmissense 1VUS (1)0.000008
25. c.15369_15371delGTT inframe 1VUS - favor pathogenic (1)0.000000
26. c.62780G>A p.R20927Hmissense 1VUS (1)0.000008
27. c.54167G>A p.R18056Qmissense 1VUS (1)0.000026
28. c.77816A>C p.Asp25939Alamissense 1VUS (1)0.000000
29. c.72985A>G p.Asn24329Aspmissense 1VUS (1)0.000000
30. c.70181C>T p.T23394Mmissense 1VUS (1)0.000024
31. c.85195G>A p.E28399Kmissense 1VUS (1)0.000016
32. c.6478A>G p.T2160Amissense 1VUS (1)0.000016
33. c.20260A>G p.Lys6754Glumissense 1VUS (1)0.000000
34. c.11450G>A p.G3817Dmissense 1VUS (1)0.000017
35. c.89766G>C p.Lys29922Asnmissense 1VUS (1)0.000000
36. c.96286G>A p.A32096Tmissense 1VUS (1)0.000066
37. c.93472G>C p.Asp31158Hismissense 1VUS (1)0.000000
38. c.107285G>A p.R35762Qmissense 1VUS (1)0.000033
39. c.43019T>C p.I14340Tmissense 1VUS (1)0.000008
40. c.48395G>A p.R16132Hmissense 1VUS (1)0.000066
41. c.72488G>A p.R24163Hmissense 1VUS (1)0.000054
42. c.58982G>A p.G19661Dmissense 1VUS (1)0.000016
43. c.55139T>C p.I18380Tmissense 1VUS (1)0.000050
44. c.84523T>C p.Trp28175Argmissense 1VUS (1)0.000000
45. c.2605A>T p.T869Smissense 1VUS (1)0.000041
46. c.98296G>T p.D32766Ymissense 1VUS (1)0.000008
47. c.9674A>G p.N3225Smissense 1VUS (1)0.000024
48. c.105630A>C p.Gln35210Hismissense 1VUS (1)0.000000
49. c.98243G>A p.R32748Hmissense 1VUS (1)0.000066
50. c.102638A>G p.N34213Smissense 1VUS (1)0.000008
51. c.50647C>T p.Pro16883Sermissense 1VUS (1)0.000000
52. c.39163A>G p.Lys13055Glumissense 1VUS (1)0.000000
53. c.63632T>C p.Val21211Alamissense 1VUS (1)0.000000
54. c.58684A>G p.Ile19562Valmissense 1VUS (1)0.000000
55. c.67147G>A p.G22383Rmissense 1VUS (1)0.000058
56. c.6941T>C p.I2314Tmissense 1VUS (1)0.000008
57. c.5132C>T p.S1711Fmissense 1VUS (1)0.000016
58. c.12037G>A p.Ala4013Thrmissense 1VUS (1)0.000000
59. c.93968C>T p.A31323Vmissense 1VUS (1)0.000057
60. c.20742T>A p.Phe6914Leumissense 1VUS (1)0.000000
61. c.99434G>A p.R33145Qmissense 1VUS (1)0.000033
62. c.18663A>C p.E6221Dmissense 1VUS (1)0.000099
63. c.102428T>C p.M34143Tmissense 1VUS (1)0.000074
64. c.22386T>G p.Asp7462Glumissense 1VUS (1)0.000000
65. c.28754A>C p.Glu9585Alamissense 1VUS (1)0.000000
66. c.57415A>C p.Ile19139Leumissense 1VUS (1)0.000000
67. c.54091A>G p.S18031Gmissense 1VUS (1)0.000008
68. c.62290G>C p.Glu20764Glnmissense 1VUS (1)0.000000
69. c.64903C>T p.R21635Cmissense 1VUS (1)0.000024

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.