MYBPC3 variants in HCM cohorts

MYBPC3 gene summary
Overview of MYBPC3 in HCM

The table below lists the 1176 rare (MAF<0.0001 in ExAC) protein-altering MYBPC3 variants identified in a cohort of 6179 HCM patients (3267 patients from OMGL, 2912 patients from LMM). When this rare variant frequency of 0.19032 is compared with a background population rate of 0.01970, there is a statistically significant case excess of 0.17062 (p<0.0001), which suggests that approximately 1,058 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 (6179)▼OMGL classLMM class ExAC frequency
1. c.1504C>T p.R502Wmissense 104Pathogenic (59)Pathogenic (45)0.000024
2. c.772G>A p.E258Kmissense 68Pathogenic (47)Pathogenic (21)0.000039
3. c.2373_2374insG p.Trp792ValfsTer41frameshift 66Pathogenic (40)Pathogenic (26)0.000037
4. c.1624G>C p.E542Qmissense 41Pathogenic (24)Likely Pathogenic (17)0.000024
5. c.1928-2A>G essential splice site 30Pathogenic (10)Pathogenic (20)0.000000
6. c.655G>C p.V219Lmissense 26Likely Pathogenic (18)Likely Pathogenic (8)0.000000
7. c.2429G>A p.R810Hmissense 19VUS (11)VUS favour pathogenic (8)0.000033
8. c.2096delC frameshift 19Pathogenic (15)Pathogenic (4)0.000000
9. c.2827C>T p.R943Xnonsense 18Pathogenic (11)Pathogenic (7)0.000017
10. c.3226_3227insT frameshift 18Pathogenic (12)Pathogenic (6)0.000000
11. c.2864_2865delCT frameshift 14Pathogenic (8)Pathogenic (6)0.000000
12. c.1484G>A p.R495Qmissense 14Likely Pathogenic (4)VUS favour pathogenic (10)0.000008
13. c.1483C>G p.R495Gmissense 14Likely Pathogenic (10)Likely Pathogenic (4)0.000000
14. c.3697C>T p.Q1233Xnonsense 13Likely Pathogenic (4)Pathogenic (9)0.000008
15. c.3330+2T>G essential splice site 11Pathogenic (11)0.000000
16. c.2308G>A p.D770Nmissense 11Likely Pathogenic (5)Likely Pathogenic (6)0.000008
17. c.442G>A p.G148Rmissense 11Likely Pathogenic (4)VUS favour pathogenic (7)0.000042
18. c.927-2A>G essential splice site 10Pathogenic (8)Pathogenic (2)0.000000
19. c.2604_2605delinsA p.S871fsframeshift 10Pathogenic (8)Pathogenic (2)0.000000
20. c.3613C>T p.R1205Wmissense 10Likely Pathogenic (10)0.000016
21. c.3190+2T>G essential splice site 9Pathogenic (7)Pathogenic (2)0.000016
22. c.3771C>A p.N1257Kmissense 9Likely Pathogenic (9)0.000000
23. c.2309-2A>G essential splice site 9Pathogenic (9)0.000000
24. c.1505G>A p.R502Qmissense 8Pathogenic (2)Pathogenic (6)0.000000
25. c.2490_2491insT p.His831SerfsTer2frameshift 8Pathogenic (7)Pathogenic (1)0.000024
26. c.3627+1G>A essential splice site 8Pathogenic (6)Pathogenic (2)0.000000
27. c.2670G>A p.W890Xnonsense 7Pathogenic (7)0.000000
28. c.2905+1G>A essential splice site 7Pathogenic (3)Pathogenic (4)0.000000
29. c.710A>C p.Y237Smissense 6Likely Pathogenic (3)Likely Pathogenic (3)0.000000
30. c.3065G>C p.R1022Pmissense 6Likely Pathogenic (5)VUS favour pathogenic (1)0.000025
31. c.2573G>A p.S858Nmissense 6Likely Pathogenic (2)VUS favour pathogenic (4)0.000000
32. c.2459G>A p.R820Qmissense 6VUS (5)Likely Pathogenic (1)0.000016
33. c.2905C>T p.Q969Xnonsense 5Pathogenic (2)Pathogenic (3)0.000000
34. c.1828G>A p.D610Nmissense 5VUS (2)VUS (3)0.000000
35. c.2267delC frameshift 5Pathogenic (5)0.000000
36. c.2556_2557delinsTCT p.Gly853fsframeshift 5Pathogenic (4)Pathogenic (1)0.000000
37. c.2610delC frameshift 5Pathogenic (5)0.000000
38. c.913_914delTT frameshift 5Pathogenic (5)0.000000
39. c.821+2T>C essential splice site 5Pathogenic (4)Pathogenic (1)0.000000
40. c.821+1G>A essential splice site 5Pathogenic (1)Pathogenic (4)0.000043
41. c.2374T>C p.W792Rmissense 5Likely Pathogenic (5)0.000000
42. c.3064C>T p.R1022Cmissense 5VUS (1)VUS favour pathogenic (4)0.000008
43. c.3277G>T p.G1093Cmissense 4VUS (3)VUS (1)0.000020
44. c.3286G>T p.E1096Xnonsense 4Pathogenic (3)Pathogenic (1)0.000000
45. c.1483C>T p.R495Wmissense 4Likely Pathogenic (2)VUS favour pathogenic (2)0.000000
46. c.2210C>T p.T737Mmissense 4VUS (3)VUS (1)0.000050
47. c.3408C>A p.Y1136Xnonsense 4Pathogenic (3)Pathogenic (1)0.000000
48. c.3763G>A p.A1255Tmissense 4VUS (3)VUS favour pathogenic (1)0.000075
49. c.3163A>T p.K1055Xnonsense 4Pathogenic (4)0.000000
50. c.2182G>T p.E728Xnonsense 4Pathogenic (4)0.000000
51. c.3181C>T p.Q1061Xnonsense 4Pathogenic (3)Pathogenic (1)0.000016
52. c.484C>T p.Q162Xnonsense 4Pathogenic (4)0.000000
53. c.3798C>G p.C1266Wmissense 4VUS (4)0.000000
54. c.26-2A>G essential splice site 4Pathogenic (4)0.000051
55. c.2873C>T p.T958Imissense 4VUS (1)VUS favour benign (3)0.000065
56. c.3742_3759dup p.Gly1248_Cys1253dupinframe 4Likely Pathogenic (4)0.000000
57. c.1591G>A p.G531Rmissense 4Likely Pathogenic (1)VUS favour pathogenic (3)0.000017
58. c.2454G>A p.W818Xnonsense 4Pathogenic (4)0.000000
59. c.1790G>A p.R597Qmissense 3VUS (1)VUS favour pathogenic (2)0.000000
60. c.2450G>A p.R817Qmissense 3VUS favour pathogenic (3)0.000016
61. c.3600_3609delCTGCTGTGCT frameshift 3Pathogenic (3)Pathogenic (0)0.000000
62. c.833delG p.Gly278GlufsX22frameshift 3Pathogenic (2)Pathogenic (1)0.000000
63. c.3190+1G>A essential splice site 3Pathogenic (3)0.000000
64. c.2558delG frameshift 3Pathogenic (1)Pathogenic (2)0.000000
65. c.1037G>A p.R346Hmissense 3VUS (1)VUS (2)0.000000
66. c.3233G>A p.W1078Xnonsense 3Pathogenic (3)0.000022
67. c.772+1G>A essential splice site 3Pathogenic (1)Pathogenic (2)0.000000
68. c.177_187del p.Glu60AlafsX49frameshift 3Pathogenic (2)Pathogenic (1)0.000000
69. c.532G>A p.V178Mmissense 3VUS (1)VUS favour pathogenic (2)0.000020
70. c.2920C>T p.Q974Xnonsense 3Pathogenic (3)0.000000
71. c.3624delC frameshift 3Pathogenic (1)Pathogenic (2)0.000000
72. c.355G>A p.E119Kmissense 3VUS (3)0.000000
73. c.1123G>A p.V375Mmissense 3VUS (3)0.000009
74. c.3491-2A>T essential splice site 3Pathogenic (3)0.000000
75. c.1828G>C p.D610Hmissense 3VUS (1)VUS favour benign (2)0.000058
76. c.2308+1G>A essential splice site 3Pathogenic (2)Pathogenic (1)0.000000
77. c.1720C>T p.R574Wmissense 3VUS (3)0.000054
78. c.3129C>A p.Y1043Xnonsense 3Pathogenic (3)0.000000
79. c.2311_2312insG p.Val771GlyfsX62frameshift 3Pathogenic (3)0.000000
80. c.3767_3769delCCA p.Thr1256delinframe 3Likely Pathogenic (3)0.000000
81. c.2545del p.Val849Serfs*30frameshift 3Pathogenic (3)0.000000
82. c.2309-1G>A essential splice site 3Pathogenic (3)0.000000
83. c.3373G>A p.V1125Mmissense 2VUS (1)VUS favour pathogenic (1)0.000022
84. c.25+1G>A essential splice site 2Pathogenic (2)0.000000
85. c.2534_2538delGCGTC frameshift 2Pathogenic (1)Pathogenic (1)0.000000
86. c.3192_3193insC p.Lys1065GlnfsX12frameshift 2Pathogenic (2)0.000000
87. c.3624_3625insC p.Lys1209GlnfsX33frameshift 2Pathogenic (2)0.000000
88. c.1090+1G>A essential splice site 2Pathogenic (1)Pathogenic (1)0.000000
89. c.2943_2947delGACCA frameshift 2Pathogenic (2)0.000000
90. c.999C>G p.Y333Xnonsense 2Pathogenic (2)0.000000
91. c.1766G>A p.R589Hmissense 2VUS (2)0.000000
92. c.3627+1G>T essential splice site 2Pathogenic (2)0.000000
93. c.3005G>A p.R1002Qmissense 2VUS (2)0.000046
94. c.373G>T p.A125Smissense 2VUS (1)VUS (1)0.000000
95. c.1999_2000delinsG p.Leu667AspfsX15frameshift 2Pathogenic (1)Pathogenic (1)0.000000
96. c.557C>T p.P186Lmissense 2VUS (2)0.000047
97. c.818G>A p.R273Hmissense 2VUS (2)0.000042
98. c.844C>T p.R282Wmissense 2Likely Pathogenic (1)VUS favour pathogenic (1)0.000000
99. c.1038_1042dupCGGCA frameshift 2Pathogenic (1)Pathogenic (1)0.000008
100. c.1895delT p.Met632ArgfsX31frameshift 2Pathogenic (2)0.000000
101. c.459delC frameshift 2Pathogenic (1)Pathogenic (1)0.000000
102. c.2882C>T p.P961Lmissense 2VUS (2)0.000048
103. c.3582_3593delGGGCTACACTGC inframe 2Likely Pathogenic (1)0.000000
104. c.2197C>T p.R733Cmissense 2Likely Pathogenic (1)VUS (1)0.000085
105. c.2269G>A p.V757Mmissense 2VUS (1)VUS (1)0.000066
106. c.3752A>G p.Y1251Cmissense 2VUS (2)0.000000
107. c.2905+2dup essential splice site 2Likely Pathogenic (2)0.000000
108. c.2524dup p.Tyr842Leufs*42frameshift 2Pathogenic (2)0.000000
109. c.1210C>T p.Q404Xnonsense 2Pathogenic (2)0.000000
110. c.3271del p.Asp1091Metfs*98frameshift 2Pathogenic (2)0.000000
111. c.932C>A p.S311Xnonsense 2Pathogenic (1)Pathogenic (1)0.000000
112. c.3455_3466del p.Ala1152_Lys1155delinframe 2Likely Pathogenic (2)0.000000
113. c.436_437insA p.Thr146AsnfsX7frameshift 2Pathogenic (2)0.000000
114. c.1869C>A p.C623Xnonsense 2Pathogenic (2)0.000000
115. c.1934C>T p.P645Lmissense 2VUS (2)0.000000
116. c.814C>T p.R272Cmissense 2VUS (2)0.000083
117. c.3470C>T p.P1157Lmissense 2VUS (2)0.000093
118. c.2526C>G p.Y842Xnonsense 2Pathogenic (2)0.000000
119. c.2320G>A p.A774Tmissense 2VUS (2)0.000000
120. c.2300A>G p.K767Rmissense 2VUS (2)0.000016
121. c.1513_1515delAAG inframe 2VUS favour pathogenic (2)0.000000
122. c.1273C>T p.Q425Xnonsense 2Pathogenic (1)Pathogenic (1)0.000000
123. c.1456T>G p.W486Gmissense 2VUS (1)Likely Pathogenic (1)0.000000
124. c.636C>G p.S212Rmissense 2VUS favour pathogenic (2)0.000000
125. c.1090+1G>T essential splice site 2Pathogenic (1)Pathogenic (1)0.000000
126. c.3253G>T p.E1085Xnonsense 2Pathogenic (1)Pathogenic (1)0.000000
127. c.1897+1G>A essential splice site 2Pathogenic (2)0.000000
128. c.1351+1G>A essential splice site 2Pathogenic (1)Pathogenic (1)0.000000
129. c.2219G>C p.G740Amissense 2VUS (2)0.000000
130. c.1021G>A p.G341Smissense 2VUS (1)VUS favour pathogenic (1)0.000025
131. c.126G>A p.W42Xnonsense 2Pathogenic (2)0.000000
132. c.3676C>T p.R1226Cmissense 2VUS (1)VUS (1)0.000058
133. c.2432A>G p.K811Rmissense 2VUS (2)0.000000
134. c.1357_1358delCC frameshift 2Pathogenic (2)0.000000
135. c.3811C>T p.R1271Xnonsense 2VUS (1)Pathogenic (1)0.000025
136. c.1863delC p.Phe621LeufsX42frameshift 2Pathogenic (2)0.000000
137. c.3751T>C p.Y1251Hmissense 2VUS (2)0.000000
138. c.1213A>G p.M405Vmissense 2VUS (1)Pathogenic (1)0.000000
139. c.1841A>G p.Y614Cmissense 2VUS (1)VUS favour pathogenic (1)0.000000
140. c.2953A>T p.K985Xnonsense 2Pathogenic (1)Pathogenic (1)0.000000
141. c.1886T>C p.L629Pmissense 2VUS (2)0.000000
142. c.2449C>T p.R817Wmissense 2VUS (1)VUS (1)0.000000
143. c.443dup p.Ala149Serfs*4frameshift 2Pathogenic (2)0.000000
144. c.747C>A p.C249Xnonsense 2Pathogenic (2)0.000000
145. c.2654C>T p.T885Mmissense 1VUS (1)0.000022
146. c.255del p.Ser86Profs*10frameshift 1Pathogenic (1)0.000000
147. c.2249C>T p.T750Mmissense 1Likely Pathogenic (1)0.000024
148. c.3452C>T p.A1151Vmissense 1VUS (1)0.000078
149. c.553_562del p.Lys185Trpfs*12frameshift 1Pathogenic (1)0.000000
150. c.2504G>T p.R835Lmissense 1Likely Pathogenic (1)0.000074
151. c.103C>T p.R35Wmissense 1VUS (1)0.000056
152. c.3614G>A p.R1205Qmissense 1VUS (1)0.000016
153. c.2737+1G>C essential splice site 1Pathogenic (1)0.000000
154. c.1377delC frameshift 1Pathogenic (1)0.000000
155. c.2048G>A p.W683Xnonsense 1Pathogenic (1)0.000000
156. c.1789C>T p.R597Wmissense 1VUS (1)0.000038
157. c.1021G>C p.G341Rmissense 1VUS (1)0.000000
158. c.3791G>A p.C1264Ymissense 1VUS (1)0.000008
159. c.3364A>T p.T1122Smissense 1Likely Pathogenic (1)0.000000
160. c.3288delG frameshift 1Pathogenic (1)0.000000
161. c.1678delG p.Asp560ThrfsX19frameshift 1Pathogenic (1)0.000000
162. c.799C>G p.L267Vmissense 1VUS (1)0.000080
163. c.3792_3793del p.Cys1264*frameshift 1Likely Pathogenic (1)0.000000
164. c.1112C>T p.P371Lmissense 1VUS (1)0.000028
165. c.2149-1G>A essential splice site 1Pathogenic (1)0.000000
166. c.188G>A p.R63Qmissense 1VUS (1)0.000039
167. c.821+1G>C essential splice site 1Pathogenic (1)0.000000
168. c.1156G>T p.E386Xnonsense 1Pathogenic (1)0.000000
169. c.333_334insT p.E112Xnonsense 1Pathogenic (1)0.000000
170. c.3297dup p.Tyr1100Valfs*49frameshift 1Pathogenic (1)0.000000
171. c.2149_2737del p.Leu717Alafs*11frameshift 1Pathogenic (1)0.000000
172. c.2906-2A>G essential splice site 1Pathogenic (1)0.000000
173. c.3614G>C p.R1205Pmissense 1Likely Pathogenic (1)0.000000
174. c.533delT p.Val178GlyfsX7frameshift 1Pathogenic (1)0.000000
175. c.2953A>G p.K985Emissense 1Pathogenic (1)0.000000
176. c.2524_2525insT p.Tyr842LeufsX42frameshift 1Pathogenic (1)0.000000
177. c.2610_2611insC p.Ser871GlnfsX13frameshift 1Pathogenic (1)0.000000
178. c.2381C>A p.P794Qmissense 1VUS (1)0.000000
179. c.1628delA frameshift 1Pathogenic (1)0.000000
180. c.1523_1525delinsT p.Gln508Leufs*22frameshift 1Pathogenic (1)0.000000
181. c.3065G>A p.R1022Hmissense 1VUS favour pathogenic (1)0.000000
182. c.2603-1G>C essential splice site 1Pathogenic (1)0.000000
183. c.2054_2067+11del p.Lys685Argfs*3frameshift 1Pathogenic (1)0.000000
184. c.2748G>A p.W916Xnonsense 1Pathogenic (1)0.000000
185. c.1418T>C p.F473Smissense 1VUS (1)0.000000
186. c.1731G>C p.W577Cmissense 1VUS (1)0.000000
187. c.853G>A p.D285Nmissense 1VUS (1)0.000000
188. c.1223+2T>C essential splice site 1Pathogenic (1)0.000000
189. c.3694A>T p.K1232Xnonsense 1Pathogenic (1)0.000000
190. c.3281A>T p.N1094Imissense 1VUS (1)0.000000
191. c.1404del p.Gln469Serfs*19frameshift 1Pathogenic (1)0.000000
192. c.1778C>T p.S593Fmissense 1VUS favour pathogenic (1)0.000034
193. c.1021_1028del p.Gly341*frameshift 1Pathogenic (1)0.000000
194. c.1672G>A p.A558Tmissense 1VUS (1)0.000008
195. c.3490+1G>A essential splice site 1Pathogenic (1)0.000000
196. c.655-2del essential splice site 1Pathogenic (1)0.000000
197. c.2312T>C p.V771Amissense 1VUS (1)0.000000
198. c.121dup p.Arg41Profs*8frameshift 1Pathogenic (1)0.000000
199. c.1090+2T>C essential splice site 1Pathogenic (1)0.000000
200. c.2518G>A p.V840Mmissense 1VUS (1)0.000016
201. c.351_352del p.Gly118Argfs*8frameshift 1Pathogenic (1)0.000000
202. c.3413G>C p.R1138Pmissense 1VUS (1)0.000000
203. c.3415G>A p.V1139Imissense 1VUS (1)0.000087
204. c.1898-1G>A essential splice site 1Pathogenic (1)0.000000
205. c.2304_2308+2delCATCGGT essential splice site 1Pathogenic (1)0.000000
206. c.1471G>A p.V491Mmissense 1VUS (1)0.000058
207. c.3083C>G p.T1028Smissense 1VUS (1)0.000000
208. c.1693A>T p.K565Xnonsense 1Pathogenic (1)0.000000
209. c.1685C>T p.A562Vmissense 1VUS (1)0.000008
210. c.1000G>T p.E334Xnonsense 1Pathogenic (1)0.000000
211. c.2723A>G p.Y908Cmissense 1VUS (1)0.000062
212. c.*26+2T>C essential splice site 1Likely Pathogenic (1)0.000000
213. c.1699_1700delGA p.Glu567GlyfsX4frameshift 1Pathogenic (1)0.000000
214. c.1153G>A p.V385Mmissense 1VUS (1)0.000010
215. c.2747G>A p.W916Xnonsense 1Pathogenic (1)0.000000
216. c.3739G>A p.D1247Nmissense 1VUS (1)0.000000
217. c.3043dup p.Ala1015Glyfs*36frameshift 1Pathogenic (1)0.000000
218. c.2394_2395insT p.Gly799TrpfsX34frameshift 1Pathogenic (1)0.000000
219. c.148A>G p.S50Gmissense 1VUS (1)0.000038
220. c.3166_3167insG p.Ala1056GlyfsX9frameshift 1Pathogenic (1)0.000000
221. c.3330+1G>C essential splice site 1Pathogenic (1)0.000000
222. c.1591G>C p.G531Rmissense 1VUS favour pathogenic (1)0.000017
223. c.1575T>G p.Y525Xnonsense 1Pathogenic (1)0.000000
224. c.2533C>T p.R845Cmissense 1VUS favour pathogenic (1)0.000000
225. c.2690_2696del p.Gly897Glufs*25frameshift 1Pathogenic (1)0.000000
226. c.3735delC frameshift 1Likely Pathogenic (1)0.000000
227. c.2965G>T p.E989Xnonsense 1Pathogenic (1)0.000000
228. c.2188del p.Thr730Profs*24frameshift 1Pathogenic (1)0.000000
229. c.2807dup p.Ala938Glyfs*113frameshift 1Pathogenic (1)0.000000
230. c.2163delC p.Glu722ArgfsX32frameshift 1Pathogenic (1)0.000000
231. c.2429_2503delins23 p.Arg810Profs*10frameshift 1Pathogenic (1)0.000000
232. c.1224-2A>G essential splice site 1Pathogenic (1)0.000000
233. c.3476_3479dupTTAT p.Pro1161TyrfsX9frameshift 1Pathogenic (1)0.000000
234. c.3206C>A p.P1069Hmissense 1Likely Pathogenic (1)0.000000
235. c.2525A>G p.Y842Cmissense 1VUS (1)0.000000
236. c.1455A>T p.K485Nmissense 1VUS (1)0.000000
237. c.2013_2016delinsGG p.Pro672AspfsX20frameshift 1Pathogenic (1)0.000000
238. c.1797del p.His599Glnfs*3frameshift 1Pathogenic (1)0.000000
239. c.1231A>G p.I411Vmissense 1VUS (1)0.000000
240. c.431_432delGT p.Gly144AlafsX8frameshift 1Pathogenic (1)0.000000
241. c.2247C>A p.Y749Xnonsense 1Pathogenic (1)0.000000
242. c.1120C>T p.Q374Xnonsense 1Pathogenic (1)0.000000
243. c.1960C>T p.R654Cmissense 1VUS favour benign (1)0.000008
244. c.391dup p.Ala131Glyfs*22frameshift 1Pathogenic (1)0.000000
245. c.932C>T p.S311Lmissense 1VUS (1)0.000000
246. c.566T>A p.V189Dmissense 1VUS (1)0.000000
247. c.1352_1353del p.Glu451Alafs*23frameshift 1Pathogenic (1)0.000000
248. c.1397T>A p.M466Kmissense 1VUS (1)0.000008
249. c.731del p.Lys244Argfs*56frameshift 1Pathogenic (1)0.000000
250. c.2436G>T p.K812Nmissense 1VUS (1)0.000000
251. c.177dup p.Glu60Argfs*53frameshift 1Pathogenic (1)0.000000
252. c.2503C>T p.R835Cmissense 1VUS (1)0.000024
253. c.1A>T p.Met1?missense 1Likely Pathogenic (1)0.000000
254. c.2308+1G>T essential splice site 1Pathogenic (1)0.000000
255. c.2828G>A p.R943Qmissense 1VUS (1)0.000025
256. c.241G>T p.V81Fmissense 1VUS (1)0.000000
257. c.2198G>A p.R733Hmissense 1VUS (1)0.000034
258. c.3316G>A p.D1106Nmissense 1VUS (1)0.000061
259. c.3825A>G p.X1275TrpextX77nonsense 1Likely Pathogenic (1)0.000000
260. c.994G>A p.E332Kmissense 1VUS (1)0.000009
261. c.1168delC frameshift 1Pathogenic (1)0.000000
262. c.451G>A p.D151Nmissense 1VUS (1)0.000041
263. c.2265C>A p.N755Kmissense 1Pathogenic (1)0.000000
264. c.1303C>T p.Q435Xnonsense 1Pathogenic (1)0.000000
265. c.1624+2T>C essential splice site 1Pathogenic (1)0.000000
266. c.104G>A p.R35Qmissense 1VUS (1)0.000079
267. c.2833_2834delCG frameshift 1Pathogenic (1)0.000000
268. c.3357C>A p.Y1119Xnonsense 1Pathogenic (1)0.000000
269. c.743_746delACTG frameshift 1Pathogenic (1)0.000000
270. c.1458-1G>A essential splice site 1Pathogenic (1)0.000000
271. c.187C>T p.R63Wmissense 1VUS (1)0.000077
272. c.551_552insT p.Lys185GlufsX56frameshift 1Pathogenic (1)0.000000
273. c.2541C>A p.Y847Xnonsense 1Pathogenic (1)0.000000
274. c.3331-1G>A essential splice site 1Pathogenic (1)0.000000
275. c.1586C>G p.T529Smissense 1VUS favour pathogenic (1)0.000000
276. c.2718_2719dup p.Glu907Glyfs*18frameshift 1Pathogenic (1)0.000000
277. c.1343T>C p.F448Smissense 1Likely Pathogenic (1)0.000000
278. c.1924C>T p.Q642Xnonsense 1Pathogenic (1)0.000000
279. c.966G>A p.W322Xnonsense 1Pathogenic (1)0.000000
280. c.2065C>T p.Q689Xnonsense 1Pathogenic (1)0.000000
281. c.1505G>T p.R502Lmissense 1VUS favour pathogenic (1)0.000000
282. c.2371C>T p.Q791Xnonsense 1Pathogenic (1)0.000000
283. c.1458G>A p.W486Xnonsense 1Pathogenic (1)0.000000
284. c.3548T>G p.F1183Cmissense 1Likely Pathogenic (1)0.000000
285. c.2584C>T p.Q862Xnonsense 1Pathogenic (1)0.000000
286. c.821+2T>G essential splice site 1Pathogenic (1)0.000000
287. c.1569dup p.His524Alafs*7frameshift 1Pathogenic (1)0.000000
288. c.1201C>T p.Q401Xnonsense 1Pathogenic (1)0.000000
289. c.2517_2538del p.Val840ThrfsX32frameshift 1Pathogenic (1)0.000000
290. c.1376_1377del p.Pro459Leufs*15frameshift 1Pathogenic (1)0.000000
291. c.223G>A p.D75Nmissense 1VUS favour pathogenic (1)0.000091
292. c.256_258del p.Ser86delinframe 1VUS (1)0.000000
293. c.611_618delinsT p.Gly204Valfs*94frameshift 1Pathogenic (1)0.000000
294. c.100_110dup p.Val38Serfs*5frameshift 1Pathogenic (1)0.000000
295. c.713G>A p.R238Hmissense 1VUS (1)0.000074
296. c.3617delG frameshift 1Pathogenic (1)0.000000
297. c.2560A>G p.M854Vmissense 1VUS (1)0.000000
298. c.2995-1G>A essential splice site 1Pathogenic (1)0.000000
299. c.2905+1G>C essential splice site 1Pathogenic (1)0.000000
300. c.1433C>T p.S478Lmissense 1Likely Pathogenic (1)0.000017
301. c.3098G>A p.R1033Qmissense 1VUS (1)0.000000
302. c.1800delA frameshift 1Pathogenic (1)0.000000
303. c.1072G>A p.D358Nmissense 1VUS (1)0.000008
304. c.3746G>T p.G1249Vmissense 1VUS (1)0.000000
305. c.3068_3069insA p.Asn1023LysfsX28frameshift 1Pathogenic (1)0.000000
306. c.2113_2114insA p.Thr705AsnfsX3frameshift 1Pathogenic (1)0.000000
307. c.506-1G>A essential splice site 1Pathogenic (1)0.000000
308. c.1351+2T>C essential splice site 1Pathogenic (1)0.000000
309. c.811_817delTTCCGCC frameshift 1Pathogenic (1)0.000000
310. c.2738-2A>G essential splice site 1Pathogenic (1)0.000000
311. c.2875_2876delAC p.Thr959GlyfsX91frameshift 1Pathogenic (1)0.000000
312. c.3728C>G p.P1243Rmissense 1VUS (1)0.000000
313. c.3690_3691delCA p.Phe1230LeufsX11frameshift 1Pathogenic (1)0.000000
314. c.2968C>G p.P990Amissense 1Likely Pathogenic (1)0.000000
315. c.2437A>T p.K813Xnonsense 1Pathogenic (1)0.000000
316. c.49C>T p.R17Wmissense 1VUS (1)0.000023
317. c.3316del p.Asp1106Thrfs*83frameshift 1Pathogenic (1)0.000000
318. c.2502del p.Arg835Alafs*2frameshift 1Pathogenic (1)0.000000
319. c.3476_3477delTT frameshift 1Pathogenic (1)0.000000
320. c.290C>T p.A97Vmissense 1VUS favour pathogenic (1)0.000000
321. c.2603-2_2603-1delinsGA essential splice site 1Pathogenic (1)0.000000
322. c.3797G>A p.C1266Ymissense 1Likely Pathogenic (1)0.000000
323. c.2161_2168del p.Thr721Profs*23frameshift 1Pathogenic (1)0.000000
324. c.2780_2781delCA frameshift 1Pathogenic (1)0.000000
325. c.993_994insT p.E332Xnonsense 1Pathogenic (1)0.000000
326. c.2789del p.Leu930Argfs*2frameshift 1Pathogenic (1)0.000000
327. c.2528_2536delAGATGCGCG p.Glu843_Arg845delinframe 1Pathogenic (1)0.000000
328. c.436A>C p.T146Pmissense 1VUS (1)0.000000
329. c.1224-1G>T essential splice site 1Pathogenic (1)0.000000
330. c.481C>A p.P161Tmissense 1VUS favour pathogenic (1)0.000041
331. c.506-1G>T essential splice site 1Pathogenic (1)0.000000
332. c.2234A>G p.D745Gmissense 1VUS (1)0.000000
333. c.326C>T p.A109Vmissense 1VUS (1)0.000000
334. c.1405C>T p.Q469Xnonsense 1Pathogenic (1)0.000000
335. c.2040_2041insT p.Val681CysfsX12frameshift 1Pathogenic (1)0.000000
336. c.1080G>C p.K360Nmissense 1VUS (1)0.000000
337. c.3580G>A p.A1194Tmissense 1VUS (1)0.000008
338. c.1188G>T p.W396Cmissense 1VUS (1)0.000000
339. c.1756C>G p.P586Amissense 1Likely Pathogenic (1)0.000000
340. c.3335G>A p.W1112Xnonsense 1Pathogenic (1)0.000000
341. c.3656T>C p.L1219Pmissense 1VUS (1)0.000000
342. c.1097A>C p.Q366Pmissense 1VUS (1)0.000000
343. c.3019T>C p.W1007Rmissense 1VUS (1)0.000000
344. c.365C>A p.A122Dmissense 1VUS (1)0.000000
345. c.931T>A p.S311Tmissense 1VUS (1)0.000000
346. c.1540A>G p.I514Vmissense 1VUS (1)0.000008
347. c.3572C>T p.S1191Lmissense 1VUS (1)0.000016
348. c.701C>A p.T234Nmissense 1Likely Pathogenic (1)0.000000
349. c.3257G>A p.W1086Xnonsense 1Pathogenic (1)0.000021
350. c.1358C>T p.P453Lmissense 1VUS (1)0.000008
351. c.1624+1G>A essential splice site 1Pathogenic (1)0.000000
352. c.3049G>A p.E1017Kmissense 1VUS favour benign (1)0.000085
353. c.2909G>A p.R970Qmissense 1Likely Pathogenic (1)0.000032
354. c.211_212delinsTA p.Val71*frameshift 1Pathogenic (1)0.000000
355. c.2938C>T p.R980Cmissense 1VUS (1)0.000062
356. c.2030C>T p.P677Lmissense 1VUS (1)0.000000
357. c.2170C>T p.R724Wmissense 1VUS (1)0.000019
358. c.631G>A p.D211Nmissense 1VUS (1)0.000009
359. c.1294G>A p.A432Tmissense 1VUS (1)0.000037
360. c.3G>C p.Met1?missense 1Likely Pathogenic (1)0.000000
361. c.982delG frameshift 1Pathogenic (1)0.000000
362. c.2557G>A p.G853Smissense 1VUS (1)0.000008
363. c.1291G>A p.D431Nmissense 1VUS (1)0.000028
364. c.146_148delTCA p.Ile49delinframe 1VUS (1)0.000039
365. c.3040delC p.Leu1014TrpfsX6frameshift 1Pathogenic (1)0.000000
366. c.3334_3351del p.Trp1112_Glu1117delinframe 1Likely Pathogenic (1)0.000000
367. c.711C>A p.Y237Xnonsense 1Pathogenic (1)0.000000
368. c.655-1G>A essential splice site 1Pathogenic (1)0.000000
369. c.2737+2T>A essential splice site 1Pathogenic (1)0.000000
370. c.2993A>G p.Q998Rmissense 1VUS favour pathogenic (1)0.000000
371. c.3605G>A p.C1202Ymissense 1Likely Pathogenic (1)0.000000
372. c.613C>T p.Q205Xnonsense 1Pathogenic (1)0.000000
373. c.2834G>A p.R945Qmissense 1VUS (1)0.000000
374. c.3776delA frameshift 1Pathogenic (1)0.000000
375. c.2512dup p.Glu838Glyfs*46frameshift 1Pathogenic (1)0.000000
376. c.3332_3335dupAGTG p.W1112Xnonsense 1Pathogenic (1)0.000000
377. c.3256T>C p.W1086Rmissense 1VUS (1)0.000000
378. c.2708G>A p.G903Dmissense 1Likely Pathogenic (1)0.000000
379. c.2671C>T p.R891Wmissense 1Likely Pathogenic (1)0.000031
380. c.2641G>A p.V881Imissense 1VUS (1)0.000018
381. c.2939G>A p.R980Hmissense 1VUS (1)0.000000
382. c.1535T>A p.L512Qmissense 1VUS favour pathogenic (1)0.000000
383. c.1266_1267insTGAT p.Ile423*frameshift 1Pathogenic (1)0.000000
384. c.3815-1G>A essential splice site 1Pathogenic (1)0.000000
385. c.1892delT frameshift 1Pathogenic (1)0.000000
386. c.1457G>A p.W486Xnonsense 1Pathogenic (1)0.000000
387. c.3753T>G p.Y1251Xnonsense 1Pathogenic (1)0.000000
388. c.3742G>A p.G1248Rmissense 1VUS (1)0.000033
389. c.518C>A p.T173Nmissense 1VUS (1)0.000000
390. c.1359del p.Val454Cysfs*12frameshift 1Pathogenic (1)0.000000
391. c.3605delG frameshift 1Pathogenic (1)0.000000
392. c.1950C>G p.D650Emissense 1VUS (1)0.000000
393. c.3713T>C p.L1238Pmissense 1Likely Pathogenic (1)0.000000
394. c.1174G>T p.A392Smissense 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. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.