TNNI3 variants in HCM cohorts

The table below lists the 72 rare (MAF<0.0001 in ExAC) protein-altering TNNI3 variants identified in a cohort of 3135 HCM patients. When this rare variant frequency of 0.02297 is compared with a background population rate of 0.00228, there is a statistically significant case excess of 0.02069 (p<0.0001), which suggests that approximately 65 of these variants may be pathogenic.

Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM

No. Variant (CDS) Variant (Protein) Variant Type Cases (3135)OMGL class ExAC frequency
1. c.433C>T p.R145Wmissense 10Pathogenic0.000008
2. c.484C>T p.R162Wmissense 7VUS0.000033
3. c.422G>A p.R141Qmissense 6Likely Pathogenic0.000000
4. c.485G>A p.R162Qmissense 4VUS0.000024
5. c.586G>A p.D196Nmissense 4Likely Pathogenic0.000008
6. c.407G>A p.R136Qmissense 3Likely Pathogenic0.000008
7. c.470C>T p.A157Vmissense 3Likely Pathogenic0.000000
8. c.596G>A p.S199Nmissense 2Likely Pathogenic0.000000
9. c.433C>G p.R145Gmissense 2Pathogenic0.000000
10. c.538del p.Asp180Thrfs*19frameshift 2Pathogenic0.000000
11. c.557G>A p.R186Qmissense 2Pathogenic0.000000
12. c.383T>A p.L128Qmissense 1VUS0.000000
13. c.549G>C p.K183Nmissense 1Likely Pathogenic0.000000
14. c.626A>C p.E209Amissense 1Likely Pathogenic0.000000
15. c.488C>G p.A163Gmissense 1VUS0.000000
16. c.593T>G p.L198Rmissense 1VUS0.000000
17. c.532A>G p.K178Emissense 1Pathogenic0.000000
18. c.607G>C p.G203Rmissense 1Likely Pathogenic0.000000
19. c.285C>A p.D95Emissense 1VUS0.000000
20. c.439G>C p.V147Lmissense 1VUS0.000008
21. c.506del p.Leu169Argfs*8frameshift 1VUS0.000000
22. c.581A>C p.N194Tmissense 1VUS0.000008
23. c.292C>T p.R98Xnonsense 1VUS0.000091
24. c.379G>C p.D127Hmissense 1VUS0.000000
25. c.625G>A p.E209Kmissense 1VUS0.000000
26. c.590C>G p.A197Gmissense 1VUS0.000000
27. c.390G>C p.Q130Hmissense 1VUS0.000000
28. c.573G>A p.W191Xnonsense 1VUS0.000000
29. c.511G>A p.A171Tmissense 1Likely Pathogenic0.000000
30. c.602T>C p.M201Tmissense 1Likely Pathogenic0.000000
31. c.431T>C p.L144Pmissense 1Likely Pathogenic0.000000
32. c.605A>C p.E202Amissense 1VUS0.000000
33. c.231C>A p.S77Rmissense 1VUS0.000000
34. c.490A>G p.K164Emissense 1VUS0.000000
35. c.338del p.Asp113Alafs*2frameshift 1Pathogenic0.000000
36. c.611G>A p.R204Hmissense 1Likely Pathogenic0.000000
37. c.512C>A p.A171Dmissense 1VUS0.000000
38. c.389A>G p.Q130Rmissense 1Likely Pathogenic0.000000


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