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

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.