MYH7 variants in DCM cohorts


The table below lists the 70 rare (MAF<0.0001 in ExAC) protein-altering MYH7 variants identified in a cohort of 1315 DCM patients (559 patients from OMGL, 756 patients from LMM). When this rare variant frequency of 0.05323 is compared with a background population rate of 0.01398, there is a statistically significant case excess of 0.03925 (p<0.0001), which suggests that approximately 52 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 (1315)OMGL classLMM class ExAC frequency
1. c.1405G>T p.D469Ymissense 2Likely Pathogenic (2)0.000000
2. c.5530G>A p.E1844Kmissense 2VUS (2)0.000008
3. c.431G>T p.G144Vmissense 2Likely Pathogenic (2)0.000000
4. c.1597A>G p.I533Vmissense 2Likely Pathogenic (2)0.000000
5. c.1106G>A p.R369Qmissense 2Likely Pathogenic (2)0.000000
6. c.4300C>T p.R1434Cmissense 2Likely Pathogenic (2)0.000000
7. c.2711G>A p.R904Hmissense 2Likely Pathogenic (2)0.000000
8. c.532G>A p.G178Rmissense 2Likely Pathogenic (2)0.000000
9. c.2678C>T p.A893Vmissense 2VUS favour pathogenic (2)0.000000
10. c.3856G>A p.E1286Kmissense 2Likely Pathogenic (2)0.000016
11. c.1791C>A p.N597Kmissense 1Likely Pathogenic (1)0.000000
12. c.4411C>T p.Q1471Xnonsense 1VUS favour pathogenic (1)0.000000
13. c.835G>A p.A279Tmissense 1VUS favour pathogenic (1)0.000000
14. c.5380C>G p.Q1794Emissense 1Likely Pathogenic (1)0.000000
15. c.4638G>T p.E1546Dmissense 1VUS (1)0.000000
16. c.1888C>T p.P630Smissense 1VUS (1)0.000016
17. c.1045A>G p.M349Vmissense 1VUS (1)0.000024
18. c.2441T>G p.I814Smissense 1VUS (1)0.000000
19. c.3982G>A p.A1328Tmissense 1VUS favour pathogenic (1)0.000043
20. c.2710C>T p.R904Cmissense 1Pathogenic (1)0.000008
21. c.734G>A p.G245Emissense 1Likely Pathogenic (1)0.000000
22. c.2973G>T p.K991Nmissense 1VUS favour pathogenic (1)0.000000
23. c.4004C>T p.S1335Lmissense 1VUS (1)0.000033
24. c.4030C>T p.R1344Wmissense 1VUS favour pathogenic (1)0.000016
25. c.2683C>G p.Q895Emissense 1VUS (1)0.000000
26. c.5020G>T p.V1674Lmissense 1VUS (1)0.000000
27. c.1630A>G p.T544Amissense 1VUS (1)0.000016
28. c.2682A>C p.E894Dmissense 1VUS (1)0.000000
29. c.541G>A p.G181Rmissense 1Likely Pathogenic (1)0.000008
30. c.4720C>T p.R1574Wmissense 1Likely Pathogenic (1)0.000000
31. c.2171T>A p.I724Nmissense 1VUS favour pathogenic (1)0.000000
32. c.1573G>A p.E525Kmissense 1Likely Pathogenic (1)0.000000
33. c.709C>T p.R237Wmissense 1VUS (1)0.000008
34. c.1402T>C p.F468Lmissense 1VUS favour pathogenic (1)0.000000
35. c.5740G>A p.E1914Kmissense 1Likely Pathogenic (1)0.000000
36. c.3578G>A p.R1193Hmissense 1Likely Pathogenic (1)0.000000
37. c.5329G>A p.A1777Tmissense 1VUS (1)0.000041
38. c.3464G>A p.G1155Emissense 1VUS (1)0.000000
39. c.728G>A p.R243Hmissense 1Likely Pathogenic (1)0.000008
40. c.2015G>T p.C672Fmissense 1Likely Pathogenic (1)0.000000
41. c.4408T>C p.S1470Pmissense 1VUS favour pathogenic (1)0.000000
42. c.1700G>A p.R567Hmissense 1Likely Pathogenic (1)0.000016
43. c.4985G>A p.R1662Hmissense 1VUS favour pathogenic (1)0.000057
44. c.3455A>T p.E1152Vmissense 1Likely Pathogenic (1)0.000000
45. c.1892T>C p.I631Tmissense 1VUS (1)0.000016
46. c.742A>T p.I248Fmissense 1Likely Pathogenic (1)0.000000
47. c.4643A>T p.E1548Vmissense 1VUS (1)0.000000
48. c.184G>A p.E62Kmissense 1VUS (1)0.000008
49. c.2456G>A p.R819Qmissense 1VUS (1)0.000008
50. c.3734T>A p.L1245Qmissense 1VUS (1)0.000000
51. c.2455C>T p.R819Wmissense 1VUS (1)0.000000
52. c.1570A>G p.I524Vmissense 1Likely Pathogenic (1)0.000000
53. c.5401G>A p.E1801Kmissense 1Likely Pathogenic (1)0.000000
54. c.4348G>A p.D1450Nmissense 1Likely Pathogenic (1)0.000008
55. c.2348G>C p.R783Pmissense 1Likely Pathogenic (1)0.000000
56. c.4048G>A p.E1350Kmissense 1VUS (1)0.000000
57. c.602T>C p.I201Tmissense 1Likely Pathogenic (1)0.000000
58. c.589G>A p.V197Imissense 1VUS (1)0.000016
59. c.3284A>G p.E1095Gmissense 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.