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