MYBPC3 non-truncating variants in HCM cohorts

The table below lists the 338 rare (MAF<0.0001 in ExAC) non-truncating MYBPC3 variants identified in a cohort of 3267 HCM patients. When this rare variant frequency of 0.10346 is compared with a background population rate of 0.01884, there is a statistically significant case excess of 0.08462 (p<0.0001), which suggests that approximately 277 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 (3267)OMGL class ExAC frequency
1. c.1504C>T p.R502Wmissense 59Pathogenic0.000024
2. c.772G>A p.E258Kmissense 47Pathogenic0.000039
3. c.1624G>C p.E542Qmissense 24Pathogenic0.000024
4. c.655G>C p.V219Lmissense 18Likely Pathogenic0.000000
5. c.2429G>A p.R810Hmissense 11VUS0.000033
6. c.3613C>T p.R1205Wmissense 10Likely Pathogenic0.000016
7. c.1483C>G p.R495Gmissense 10Likely Pathogenic0.000000
8. c.3771C>A p.N1257Kmissense 9Likely Pathogenic0.000000
9. c.2459G>A p.R820Qmissense 5VUS0.000016
10. c.2308G>A p.D770Nmissense 5Likely Pathogenic0.000008
11. c.3065G>C p.R1022Pmissense 5Likely Pathogenic0.000025
12. c.442G>A p.G148Rmissense 4Likely Pathogenic0.000042
13. c.1484G>A p.R495Qmissense 4Likely Pathogenic0.000008
14. c.3798C>G p.C1266Wmissense 4VUS0.000000
15. c.1123G>A p.V375Mmissense 3VUS0.000009
16. c.710A>C p.Y237Smissense 3Likely Pathogenic0.000000
17. c.3763G>A p.A1255Tmissense 3VUS0.000075
18. c.3277G>T p.G1093Cmissense 3VUS0.000020
19. c.2210C>T p.T737Mmissense 3VUS0.000050
20. c.1720C>T p.R574Wmissense 3VUS0.000054
21. c.1505G>A p.R502Qmissense 2Pathogenic0.000000
22. c.1886T>C p.L629Pmissense 2VUS0.000000
23. c.1483C>T p.R495Wmissense 2Likely Pathogenic0.000000
24. c.3752A>G p.Y1251Cmissense 2VUS0.000000
25. c.3455_3466del p.Ala1152_Lys1155delinframe 2Likely Pathogenic0.000000
26. c.3470C>T p.P1157Lmissense 2VUS0.000093
27. c.2432A>G p.K811Rmissense 2VUS0.000000
28. c.1828G>A p.D610Nmissense 2VUS0.000000
29. c.2219G>C p.G740Amissense 2VUS0.000000
30. c.3005G>A p.R1002Qmissense 2VUS0.000046
31. c.557C>T p.P186Lmissense 2VUS0.000047
32. c.3751T>C p.Y1251Hmissense 2VUS0.000000
33. c.2300A>G p.K767Rmissense 2VUS0.000016
34. c.818G>A p.R273Hmissense 2VUS0.000042
35. c.2573G>A p.S858Nmissense 2Likely Pathogenic0.000000
36. c.3582_3593delGGGCTACACTGC inframe 2Likely Pathogenic0.000000
37. c.1456T>G p.W486Gmissense 1VUS0.000000
38. c.1789C>T p.R597Wmissense 1VUS0.000038
39. c.532G>A p.V178Mmissense 1VUS0.000020
40. c.1213A>G p.M405Vmissense 1VUS0.000000
41. c.1021G>A p.G341Smissense 1VUS0.000025
42. c.3739G>A p.D1247Nmissense 1VUS0.000000
43. c.3206C>A p.P1069Hmissense 1Likely Pathogenic0.000000
44. c.1A>T p.Met1?missense 1Likely Pathogenic0.000000
45. c.1174G>T p.A392Smissense 1VUS0.000000
46. c.2381C>A p.P794Qmissense 1VUS0.000000
47. c.3019T>C p.W1007Rmissense 1VUS0.000000
48. c.3614G>A p.R1205Qmissense 1VUS0.000016
49. c.2873C>T p.T958Imissense 1VUS0.000065
50. c.2269G>A p.V757Mmissense 1VUS0.000066
51. c.3064C>T p.R1022Cmissense 1VUS0.000008
52. c.1471G>A p.V491Mmissense 1VUS0.000058
53. c.2197C>T p.R733Cmissense 1Likely Pathogenic0.000085
54. c.799C>G p.L267Vmissense 1VUS0.000080
55. c.1037G>A p.R346Hmissense 1VUS0.000000
56. c.1291G>A p.D431Nmissense 1VUS0.000028
57. c.3334_3351del p.Trp1112_Glu1117delinframe 1Likely Pathogenic0.000000
58. c.844C>T p.R282Wmissense 1Likely Pathogenic0.000000
59. c.188G>A p.R63Qmissense 1VUS0.000039
60. c.1455A>T p.K485Nmissense 1VUS0.000000
61. c.2834G>A p.R945Qmissense 1VUS0.000000
62. c.256_258del p.Ser86delinframe 1VUS0.000000
63. c.701C>A p.T234Nmissense 1Likely Pathogenic0.000000
64. c.3676C>T p.R1226Cmissense 1VUS0.000058
65. c.2504G>T p.R835Lmissense 1Likely Pathogenic0.000074
66. c.1112C>T p.P371Lmissense 1VUS0.000028
67. c.1433C>T p.S478Lmissense 1Likely Pathogenic0.000017
68. c.49C>T p.R17Wmissense 1VUS0.000023
69. c.994G>A p.E332Kmissense 1VUS0.000009
70. c.1153G>A p.V385Mmissense 1VUS0.000010
71. c.3728C>G p.P1243Rmissense 1VUS0.000000
72. c.1756C>G p.P586Amissense 1Likely Pathogenic0.000000
73. c.146_148delTCA p.Ile49delinframe 1VUS0.000039
74. c.2968C>G p.P990Amissense 1Likely Pathogenic0.000000
75. c.3713T>C p.L1238Pmissense 1Likely Pathogenic0.000000
76. c.1097A>C p.Q366Pmissense 1VUS0.000000
77. c.2449C>T p.R817Wmissense 1VUS0.000000
78. c.1841A>G p.Y614Cmissense 1VUS0.000000
79. c.3373G>A p.V1125Mmissense 1VUS0.000022
80. c.2265C>A p.N755Kmissense 1Pathogenic0.000000
81. c.2030C>T p.P677Lmissense 1VUS0.000000
82. c.1591G>A p.G531Rmissense 1Likely Pathogenic0.000017
83. c.1790G>A p.R597Qmissense 1VUS0.000000
84. c.1021G>C p.G341Rmissense 1VUS0.000000
85. c.187C>T p.R63Wmissense 1VUS0.000077
86. c.3256T>C p.W1086Rmissense 1VUS0.000000
87. c.631G>A p.D211Nmissense 1VUS0.000009
88. c.1231A>G p.I411Vmissense 1VUS0.000000
89. c.2708G>A p.G903Dmissense 1Likely Pathogenic0.000000
90. c.241G>T p.V81Fmissense 1VUS0.000000
91. c.3364A>T p.T1122Smissense 1Likely Pathogenic0.000000
92. c.3656T>C p.L1219Pmissense 1VUS0.000000
93. c.2909G>A p.R970Qmissense 1Likely Pathogenic0.000032
94. c.3452C>T p.A1151Vmissense 1VUS0.000078
95. c.2503C>T p.R835Cmissense 1VUS0.000024
96. c.2198G>A p.R733Hmissense 1VUS0.000034
97. c.1685C>T p.A562Vmissense 1VUS0.000008
98. c.1072G>A p.D358Nmissense 1VUS0.000008
99. c.373G>T p.A125Smissense 1VUS0.000000
100. c.2953A>G p.K985Emissense 1Pathogenic0.000000
101. c.365C>A p.A122Dmissense 1VUS0.000000
102. c.3614G>C p.R1205Pmissense 1Likely Pathogenic0.000000
103. c.1731G>C p.W577Cmissense 1VUS0.000000
104. c.148A>G p.S50Gmissense 1VUS0.000038
105. c.1080G>C p.K360Nmissense 1VUS0.000000
106. c.3572C>T p.S1191Lmissense 1VUS0.000016
107. c.2249C>T p.T750Mmissense 1Likely Pathogenic0.000024
108. c.1828G>C p.D610Hmissense 1VUS0.000058
109. c.3316G>A p.D1106Nmissense 1VUS0.000061


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