TTN non-truncating variants in DCM cohorts

TTN gene summary
Overview of TTN in DCM

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

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.