The table below lists the 69 rare (MAF<0.0001 in ExAC) non-truncating MYH7 variants identified in a cohort of 1315 DCM patients (559 patients from OMGL, 756 patients from LMM). When this rare variant frequency of 0.05247 is compared with a background population rate of 0.01350, there is a statistically significant case excess of 0.03897 (p<0.0001), which suggests that approximately 51 of these variants may be pathogenic.
| No. | Variant (CDS)▼ | Variant (Protein) | Variant Type▼ | Cases (1315)▼ | OMGL class | LMM class | ExAC frequency |
|---|---|---|---|---|---|---|---|
| 1. | c.5020G>T | p.V1674L | missense | 1 | VUS (1) | 0.000000 | |
| 2. | c.1597A>G | p.I533V | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 3. | c.2441T>G | p.I814S | missense | 1 | VUS (1) | 0.000000 | |
| 4. | c.2973G>T | p.K991N | missense | 1 | VUS favour pathogenic (1) | 0.000000 | |
| 5. | c.734G>A | p.G245E | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 6. | c.2710C>T | p.R904C | missense | 1 | Pathogenic (1) | 0.000008 | |
| 7. | c.2683C>G | p.Q895E | missense | 1 | VUS (1) | 0.000000 | |
| 8. | c.1630A>G | p.T544A | missense | 1 | VUS (1) | 0.000016 | |
| 9. | c.4004C>T | p.S1335L | missense | 1 | VUS (1) | 0.000033 | |
| 10. | c.4030C>T | p.R1344W | missense | 1 | VUS favour pathogenic (1) | 0.000016 | |
| 11. | c.4300C>T | p.R1434C | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 12. | c.2682A>C | p.E894D | missense | 1 | VUS (1) | 0.000000 | |
| 13. | c.541G>A | p.G181R | missense | 1 | Likely Pathogenic (1) | 0.000008 | |
| 14. | c.1106G>A | p.R369Q | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 15. | c.2171T>A | p.I724N | missense | 1 | VUS favour pathogenic (1) | 0.000000 | |
| 16. | c.1573G>A | p.E525K | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 17. | c.4720C>T | p.R1574W | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 18. | c.3578G>A | p.R1193H | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 19. | c.709C>T | p.R237W | missense | 1 | VUS (1) | 0.000008 | |
| 20. | c.1402T>C | p.F468L | missense | 1 | VUS favour pathogenic (1) | 0.000000 | |
| 21. | c.5740G>A | p.E1914K | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 22. | c.3464G>A | p.G1155E | missense | 1 | VUS (1) | 0.000000 | |
| 23. | c.1892T>C | p.I631T | missense | 1 | VUS (1) | 0.000016 | |
| 24. | c.728G>A | p.R243H | missense | 1 | Likely Pathogenic (1) | 0.000008 | |
| 25. | c.5329G>A | p.A1777T | missense | 1 | VUS (1) | 0.000041 | |
| 26. | c.2015G>T | p.C672F | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 27. | c.1700G>A | p.R567H | missense | 1 | Likely Pathogenic (1) | 0.000016 | |
| 28. | c.3455A>T | p.E1152V | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 29. | c.3982G>A | p.A1328T | missense | 1 | VUS favour pathogenic (1) | 0.000043 | |
| 30. | c.742A>T | p.I248F | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 31. | c.4985G>A | p.R1662H | missense | 1 | VUS favour pathogenic (1) | 0.000057 | |
| 32. | c.2711G>A | p.R904H | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 33. | c.4348G>A | p.D1450N | missense | 1 | Likely Pathogenic (1) | 0.000008 | |
| 34. | c.3734T>A | p.L1245Q | missense | 1 | VUS (1) | 0.000000 | |
| 35. | c.4643A>T | p.E1548V | missense | 1 | VUS (1) | 0.000000 | |
| 36. | c.184G>A | p.E62K | missense | 1 | VUS (1) | 0.000008 | |
| 37. | c.2456G>A | p.R819Q | missense | 1 | VUS (1) | 0.000008 | |
| 38. | c.532G>A | p.G178R | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 39. | c.1570A>G | p.I524V | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 40. | c.2455C>T | p.R819W | missense | 1 | VUS (1) | 0.000000 | |
| 41. | c.2348G>C | p.R783P | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 42. | c.2678C>T | p.A893V | missense | 2 | VUS favour pathogenic (2) | 0.000000 | |
| 43. | c.5401G>A | p.E1801K | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 44. | c.602T>C | p.I201T | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 45. | c.4048G>A | p.E1350K | missense | 1 | VUS (1) | 0.000000 | |
| 46. | c.3856G>A | p.E1286K | missense | 2 | Likely Pathogenic (2) | 0.000016 | |
| 47. | c.1405G>T | p.D469Y | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 48. | c.3284A>G | p.E1095G | missense | 1 | VUS (1) | 0.000000 | |
| 49. | c.589G>A | p.V197I | missense | 1 | VUS (1) | 0.000016 | |
| 50. | c.431G>T | p.G144V | missense | 2 | Likely Pathogenic (2) | 0.000000 | |
| 51. | c.1791C>A | p.N597K | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 52. | c.4408T>C | p.S1470P | missense | 1 | VUS favour pathogenic (1) | 0.000000 | |
| 53. | c.835G>A | p.A279T | missense | 1 | VUS favour pathogenic (1) | 0.000000 | |
| 54. | c.5380C>G | p.Q1794E | missense | 1 | Likely Pathogenic (1) | 0.000000 | |
| 55. | c.1045A>G | p.M349V | missense | 1 | VUS (1) | 0.000024 | |
| 56. | c.5530G>A | p.E1844K | missense | 2 | VUS (2) | 0.000008 | |
| 57. | c.4638G>T | p.E1546D | missense | 1 | VUS (1) | 0.000000 | |
| 58. | c.1888C>T | p.P630S | missense | 1 | VUS (1) | 0.000016 |
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.
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