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