MYH7 non-truncating variants in DCM cohorts


The table below lists the 44 rare (MAF<0.0001 in ExAC) non-truncating MYH7 variants identified in a cohort of 756 DCM patients. When this rare variant frequency of 0.05820 is compared with a background population rate of 0.01350, there is a statistically significant case excess of 0.04470 (p<0.0001), which suggests that approximately 34 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 (756)LMM class ExAC frequency
1. c.1597A>G p.I533Vmissense 2Likely Pathogenic0.000000
2. c.2711G>A p.R904Hmissense 2Likely Pathogenic0.000000
3. c.1106G>A p.R369Qmissense 2Likely Pathogenic0.000000
4. c.2678C>T p.A893Vmissense 2VUS favour pathogenic0.000000
5. c.1405G>T p.D469Ymissense 2Likely Pathogenic0.000000
6. c.3856G>A p.E1286Kmissense 2Likely Pathogenic0.000016
7. c.1573G>A p.E525Kmissense 1Likely Pathogenic0.000000
8. c.4720C>T p.R1574Wmissense 1Likely Pathogenic0.000000
9. c.1791C>A p.N597Kmissense 1Likely Pathogenic0.000000
10. c.5740G>A p.E1914Kmissense 1Likely Pathogenic0.000000
11. c.3578G>A p.R1193Hmissense 1Likely Pathogenic0.000000
12. c.709C>T p.R237Wmissense 1VUS0.000008
13. c.1402T>C p.F468Lmissense 1VUS favour pathogenic0.000000
14. c.1892T>C p.I631Tmissense 1VUS0.000016
15. c.3982G>A p.A1328Tmissense 1VUS favour pathogenic0.000043
16. c.742A>T p.I248Fmissense 1Likely Pathogenic0.000000
17. c.4985G>A p.R1662Hmissense 1VUS favour pathogenic0.000057
18. c.2973G>T p.K991Nmissense 1VUS favour pathogenic0.000000
19. c.4348G>A p.D1450Nmissense 1Likely Pathogenic0.000008
20. c.3734T>A p.L1245Qmissense 1VUS0.000000
21. c.184G>A p.E62Kmissense 1VUS0.000008
22. c.2171T>A p.I724Nmissense 1VUS favour pathogenic0.000000
23. c.5401G>A p.E1801Kmissense 1Likely Pathogenic0.000000
24. c.602T>C p.I201Tmissense 1Likely Pathogenic0.000000
25. c.4408T>C p.S1470Pmissense 1VUS favour pathogenic0.000000
26. c.1700G>A p.R567Hmissense 1Likely Pathogenic0.000016
27. c.835G>A p.A279Tmissense 1VUS favour pathogenic0.000000
28. c.5380C>G p.Q1794Emissense 1Likely Pathogenic0.000000
29. c.3455A>T p.E1152Vmissense 1Likely Pathogenic0.000000
30. c.1888C>T p.P630Smissense 1VUS0.000016
31. c.1570A>G p.I524Vmissense 1Likely Pathogenic0.000000
32. c.734G>A p.G245Emissense 1Likely Pathogenic0.000000
33. c.2348G>C p.R783Pmissense 1Likely Pathogenic0.000000
34. c.2710C>T p.R904Cmissense 1Pathogenic0.000008
35. c.2683C>G p.Q895Emissense 1VUS0.000000
36. c.1630A>G p.T544Amissense 1VUS0.000016
37. c.4030C>T p.R1344Wmissense 1VUS favour pathogenic0.000016

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.