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