MYBPC3 variants in HCM cohorts

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 class	LMM class	ExAC frequency
1.	c.1504C>T	p.R502W	missense	104	Pathogenic (59)	Pathogenic (45)	0.000024
2.	c.772G>A	p.E258K	missense	68	Pathogenic (47)	Pathogenic (21)	0.000039
3.	c.2373_2374insG	p.Trp792ValfsTer41	frameshift	66	Pathogenic (40)	Pathogenic (26)	0.000037
4.	c.1624G>C	p.E542Q	missense	41	Pathogenic (24)	Likely Pathogenic (17)	0.000024
5.	c.1928-2A>G		essential splice site	30	Pathogenic (10)	Pathogenic (20)	0.000000
6.	c.655G>C	p.V219L	missense	26	Likely Pathogenic (18)	Likely Pathogenic (8)	0.000000
7.	c.2429G>A	p.R810H	missense	19	VUS (11)	VUS favour pathogenic (8)	0.000033
8.	c.2096delC		frameshift	19	Pathogenic (15)	Pathogenic (4)	0.000000
9.	c.2827C>T	p.R943X	nonsense	18	Pathogenic (11)	Pathogenic (7)	0.000017
10.	c.3226_3227insT		frameshift	18	Pathogenic (12)	Pathogenic (6)	0.000000
11.	c.2864_2865delCT		frameshift	14	Pathogenic (8)	Pathogenic (6)	0.000000
12.	c.1484G>A	p.R495Q	missense	14	Likely Pathogenic (4)	VUS favour pathogenic (10)	0.000008
13.	c.1483C>G	p.R495G	missense	14	Likely Pathogenic (10)	Likely Pathogenic (4)	0.000000
14.	c.3697C>T	p.Q1233X	nonsense	13	Likely Pathogenic (4)	Pathogenic (9)	0.000008
15.	c.3330+2T>G		essential splice site	11		Pathogenic (11)	0.000000
16.	c.2308G>A	p.D770N	missense	11	Likely Pathogenic (5)	Likely Pathogenic (6)	0.000008
17.	c.442G>A	p.G148R	missense	11	Likely Pathogenic (4)	VUS favour pathogenic (7)	0.000042
18.	c.927-2A>G		essential splice site	10	Pathogenic (8)	Pathogenic (2)	0.000000
19.	c.2604_2605delinsA	p.S871fs	frameshift	10	Pathogenic (8)	Pathogenic (2)	0.000000
20.	c.3613C>T	p.R1205W	missense	10	Likely Pathogenic (10)		0.000016
21.	c.3190+2T>G		essential splice site	9	Pathogenic (7)	Pathogenic (2)	0.000016
22.	c.3771C>A	p.N1257K	missense	9	Likely Pathogenic (9)		0.000000
23.	c.2309-2A>G		essential splice site	9		Pathogenic (9)	0.000000
24.	c.1505G>A	p.R502Q	missense	8	Pathogenic (2)	Pathogenic (6)	0.000000
25.	c.2490_2491insT	p.His831SerfsTer2	frameshift	8	Pathogenic (7)	Pathogenic (1)	0.000024
26.	c.3627+1G>A		essential splice site	8	Pathogenic (6)	Pathogenic (2)	0.000000
27.	c.2670G>A	p.W890X	nonsense	7		Pathogenic (7)	0.000000
28.	c.2905+1G>A		essential splice site	7	Pathogenic (3)	Pathogenic (4)	0.000000
29.	c.710A>C	p.Y237S	missense	6	Likely Pathogenic (3)	Likely Pathogenic (3)	0.000000
30.	c.3065G>C	p.R1022P	missense	6	Likely Pathogenic (5)	VUS favour pathogenic (1)	0.000025
31.	c.2573G>A	p.S858N	missense	6	Likely Pathogenic (2)	VUS favour pathogenic (4)	0.000000
32.	c.2459G>A	p.R820Q	missense	6	VUS (5)	Likely Pathogenic (1)	0.000016
33.	c.1828G>A	p.D610N	missense	5	VUS (2)	VUS (3)	0.000000
34.	c.2267delC		frameshift	5	Pathogenic (5)		0.000000
35.	c.913_914delTT		frameshift	5		Pathogenic (5)	0.000000
36.	c.2556_2557delinsTCT	p.Gly853fs	frameshift	5	Pathogenic (4)	Pathogenic (1)	0.000000
37.	c.2610delC		frameshift	5	Pathogenic (5)		0.000000
38.	c.821+2T>C		essential splice site	5	Pathogenic (4)	Pathogenic (1)	0.000000
39.	c.821+1G>A		essential splice site	5	Pathogenic (1)	Pathogenic (4)	0.000043
40.	c.2374T>C	p.W792R	missense	5		Likely Pathogenic (5)	0.000000
41.	c.3064C>T	p.R1022C	missense	5	VUS (1)	VUS favour pathogenic (4)	0.000008
42.	c.2905C>T	p.Q969X	nonsense	5	Pathogenic (2)	Pathogenic (3)	0.000000
43.	c.1483C>T	p.R495W	missense	4	Likely Pathogenic (2)	VUS favour pathogenic (2)	0.000000
44.	c.3742_3759dup	p.Gly1248_Cys1253dup	inframe	4		Likely Pathogenic (4)	0.000000
45.	c.3277G>T	p.G1093C	missense	4	VUS (3)	VUS (1)	0.000020
46.	c.3408C>A	p.Y1136X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000000
47.	c.3763G>A	p.A1255T	missense	4	VUS (3)	VUS favour pathogenic (1)	0.000075
48.	c.2210C>T	p.T737M	missense	4	VUS (3)	VUS (1)	0.000050
49.	c.3181C>T	p.Q1061X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000016
50.	c.3163A>T	p.K1055X	nonsense	4	Pathogenic (4)		0.000000
51.	c.26-2A>G		essential splice site	4		Pathogenic (4)	0.000051
52.	c.2182G>T	p.E728X	nonsense	4		Pathogenic (4)	0.000000
53.	c.2873C>T	p.T958I	missense	4	VUS (1)	VUS favour benign (3)	0.000065
54.	c.484C>T	p.Q162X	nonsense	4	Pathogenic (4)		0.000000
55.	c.1591G>A	p.G531R	missense	4	Likely Pathogenic (1)	VUS favour pathogenic (3)	0.000017
56.	c.2454G>A	p.W818X	nonsense	4		Pathogenic (4)	0.000000
57.	c.3798C>G	p.C1266W	missense	4	VUS (4)		0.000000
58.	c.3286G>T	p.E1096X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000000
59.	c.1720C>T	p.R574W	missense	3	VUS (3)		0.000054
60.	c.1790G>A	p.R597Q	missense	3	VUS (1)	VUS favour pathogenic (2)	0.000000
61.	c.2450G>A	p.R817Q	missense	3		VUS favour pathogenic (3)	0.000016
62.	c.3129C>A	p.Y1043X	nonsense	3	Pathogenic (3)		0.000000
63.	c.2311_2312insG	p.Val771GlyfsX62	frameshift	3		Pathogenic (3)	0.000000
64.	c.3600_3609delCTGCTGTGCT		frameshift	3	Pathogenic (3)	Pathogenic (0)	0.000000
65.	c.3767_3769delCCA	p.Thr1256del	inframe	3		Likely Pathogenic (3)	0.000000
66.	c.2545del	p.Val849Serfs*30	frameshift	3	Pathogenic (3)		0.000000
67.	c.2309-1G>A		essential splice site	3	Pathogenic (3)		0.000000
68.	c.3190+1G>A		essential splice site	3		Pathogenic (3)	0.000000
69.	c.2558delG		frameshift	3	Pathogenic (1)	Pathogenic (2)	0.000000
70.	c.3233G>A	p.W1078X	nonsense	3		Pathogenic (3)	0.000022
71.	c.833delG	p.Gly278GlufsX22	frameshift	3	Pathogenic (2)	Pathogenic (1)	0.000000
72.	c.532G>A	p.V178M	missense	3	VUS (1)	VUS favour pathogenic (2)	0.000020
73.	c.3624delC		frameshift	3	Pathogenic (1)	Pathogenic (2)	0.000000
74.	c.1037G>A	p.R346H	missense	3	VUS (1)	VUS (2)	0.000000
75.	c.772+1G>A		essential splice site	3	Pathogenic (1)	Pathogenic (2)	0.000000
76.	c.177_187del	p.Glu60AlafsX49	frameshift	3	Pathogenic (2)	Pathogenic (1)	0.000000
77.	c.2920C>T	p.Q974X	nonsense	3		Pathogenic (3)	0.000000
78.	c.1828G>C	p.D610H	missense	3	VUS (1)	VUS favour benign (2)	0.000058
79.	c.2308+1G>A		essential splice site	3	Pathogenic (2)	Pathogenic (1)	0.000000
80.	c.355G>A	p.E119K	missense	3		VUS (3)	0.000000
81.	c.1123G>A	p.V375M	missense	3	VUS (3)		0.000009
82.	c.3491-2A>T		essential splice site	3		Pathogenic (3)	0.000000
83.	c.3676C>T	p.R1226C	missense	2	VUS (1)	VUS (1)	0.000058
84.	c.2432A>G	p.K811R	missense	2	VUS (2)		0.000000
85.	c.1090+1G>A		essential splice site	2	Pathogenic (1)	Pathogenic (1)	0.000000
86.	c.1863delC	p.Phe621LeufsX42	frameshift	2		Pathogenic (2)	0.000000
87.	c.2943_2947delGACCA		frameshift	2		Pathogenic (2)	0.000000
88.	c.3751T>C	p.Y1251H	missense	2	VUS (2)		0.000000
89.	c.2953A>T	p.K985X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
90.	c.1766G>A	p.R589H	missense	2		VUS (2)	0.000000
91.	c.1841A>G	p.Y614C	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000000
92.	c.2449C>T	p.R817W	missense	2	VUS (1)	VUS (1)	0.000000
93.	c.1886T>C	p.L629P	missense	2	VUS (2)		0.000000
94.	c.443dup	p.Ala149Serfs*4	frameshift	2	Pathogenic (2)		0.000000
95.	c.747C>A	p.C249X	nonsense	2	Pathogenic (2)		0.000000
96.	c.844C>T	p.R282W	missense	2	Likely Pathogenic (1)	VUS favour pathogenic (1)	0.000000
97.	c.25+1G>A		essential splice site	2	Pathogenic (2)		0.000000
98.	c.1038_1042dupCGGCA		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000008
99.	c.3192_3193insC	p.Lys1065GlnfsX12	frameshift	2		Pathogenic (2)	0.000000
100.	c.459delC		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
101.	c.2882C>T	p.P961L	missense	2		VUS (2)	0.000048
102.	c.3624_3625insC	p.Lys1209GlnfsX33	frameshift	2		Pathogenic (2)	0.000000
103.	c.2197C>T	p.R733C	missense	2	Likely Pathogenic (1)	VUS (1)	0.000085
104.	c.2269G>A	p.V757M	missense	2	VUS (1)	VUS (1)	0.000066
105.	c.999C>G	p.Y333X	nonsense	2		Pathogenic (2)	0.000000
106.	c.3627+1G>T		essential splice site	2	Pathogenic (2)		0.000000
107.	c.3005G>A	p.R1002Q	missense	2	VUS (2)		0.000046
108.	c.373G>T	p.A125S	missense	2	VUS (1)	VUS (1)	0.000000
109.	c.1210C>T	p.Q404X	nonsense	2		Pathogenic (2)	0.000000
110.	c.1999_2000delinsG	p.Leu667AspfsX15	frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
111.	c.932C>A	p.S311X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
112.	c.557C>T	p.P186L	missense	2	VUS (2)		0.000047
113.	c.818G>A	p.R273H	missense	2	VUS (2)		0.000042
114.	c.1869C>A	p.C623X	nonsense	2		Pathogenic (2)	0.000000
115.	c.1895delT	p.Met632ArgfsX31	frameshift	2		Pathogenic (2)	0.000000
116.	c.814C>T	p.R272C	missense	2		VUS (2)	0.000083
117.	c.3582_3593delGGGCTACACTGC		inframe	2	Likely Pathogenic (1)		0.000000
118.	c.1513_1515delAAG		inframe	2		VUS favour pathogenic (2)	0.000000
119.	c.1273C>T	p.Q425X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
120.	c.1456T>G	p.W486G	missense	2	VUS (1)	Likely Pathogenic (1)	0.000000
121.	c.636C>G	p.S212R	missense	2		VUS favour pathogenic (2)	0.000000
122.	c.1090+1G>T		essential splice site	2	Pathogenic (1)	Pathogenic (1)	0.000000
123.	c.3752A>G	p.Y1251C	missense	2	VUS (2)		0.000000
124.	c.1351+1G>A		essential splice site	2	Pathogenic (1)	Pathogenic (1)	0.000000
125.	c.2905+2dup		essential splice site	2	Likely Pathogenic (2)		0.000000
126.	c.1021G>A	p.G341S	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000025
127.	c.2524dup	p.Tyr842Leufs*42	frameshift	2	Pathogenic (2)		0.000000
128.	c.3271del	p.Asp1091Metfs*98	frameshift	2	Pathogenic (2)		0.000000
129.	c.3455_3466del	p.Ala1152_Lys1155del	inframe	2	Likely Pathogenic (2)		0.000000
130.	c.436_437insA	p.Thr146AsnfsX7	frameshift	2		Pathogenic (2)	0.000000
131.	c.1934C>T	p.P645L	missense	2		VUS (2)	0.000000
132.	c.3470C>T	p.P1157L	missense	2	VUS (2)		0.000093
133.	c.2526C>G	p.Y842X	nonsense	2	Pathogenic (2)		0.000000
134.	c.1357_1358delCC		frameshift	2		Pathogenic (2)	0.000000
135.	c.3811C>T	p.R1271X	nonsense	2	VUS (1)	Pathogenic (1)	0.000025
136.	c.2320G>A	p.A774T	missense	2		VUS (2)	0.000000
137.	c.2300A>G	p.K767R	missense	2	VUS (2)		0.000016
138.	c.1213A>G	p.M405V	missense	2	VUS (1)	Pathogenic (1)	0.000000
139.	c.1897+1G>A		essential splice site	2		Pathogenic (2)	0.000000
140.	c.3253G>T	p.E1085X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
141.	c.3373G>A	p.V1125M	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000022
142.	c.2219G>C	p.G740A	missense	2	VUS (2)		0.000000
143.	c.2534_2538delGCGTC		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
144.	c.126G>A	p.W42X	nonsense	2	Pathogenic (2)		0.000000
145.	c.2030C>T	p.P677L	missense	1	VUS (1)		0.000000
146.	c.2170C>T	p.R724W	missense	1		VUS (1)	0.000019
147.	c.3257G>A	p.W1086X	nonsense	1	Pathogenic (1)		0.000021
148.	c.1624+1G>A		essential splice site	1	Pathogenic (1)		0.000000
149.	c.3049G>A	p.E1017K	missense	1		VUS favour benign (1)	0.000085
150.	c.2909G>A	p.R970Q	missense	1	Likely Pathogenic (1)		0.000032
151.	c.211_212delinsTA	p.Val71*	frameshift	1	Pathogenic (1)		0.000000
152.	c.3288delG		frameshift	1		Pathogenic (1)	0.000000
153.	c.2938C>T	p.R980C	missense	1		VUS (1)	0.000062
154.	c.631G>A	p.D211N	missense	1	VUS (1)		0.000009
155.	c.1294G>A	p.A432T	missense	1		VUS (1)	0.000037
156.	c.3G>C	p.Met1?	missense	1		Likely Pathogenic (1)	0.000000
157.	c.982delG		frameshift	1	Pathogenic (1)		0.000000
158.	c.2557G>A	p.G853S	missense	1		VUS (1)	0.000008
159.	c.1291G>A	p.D431N	missense	1	VUS (1)		0.000028
160.	c.1156G>T	p.E386X	nonsense	1		Pathogenic (1)	0.000000
161.	c.1628delA		frameshift	1		Pathogenic (1)	0.000000
162.	c.146_148delTCA	p.Ile49del	inframe	1	VUS (1)		0.000039
163.	c.3040delC	p.Leu1014TrpfsX6	frameshift	1		Pathogenic (1)	0.000000
164.	c.3334_3351del	p.Trp1112_Glu1117del	inframe	1	Likely Pathogenic (1)		0.000000
165.	c.711C>A	p.Y237X	nonsense	1	Pathogenic (1)		0.000000
166.	c.2737+2T>A		essential splice site	1		Pathogenic (1)	0.000000
167.	c.3605G>A	p.C1202Y	missense	1		Likely Pathogenic (1)	0.000000
168.	c.613C>T	p.Q205X	nonsense	1		Pathogenic (1)	0.000000
169.	c.2834G>A	p.R945Q	missense	1	VUS (1)		0.000000
170.	c.1778C>T	p.S593F	missense	1		VUS favour pathogenic (1)	0.000034
171.	c.2512dup	p.Glu838Glyfs*46	frameshift	1	Pathogenic (1)		0.000000
172.	c.3332_3335dupAGTG	p.W1112X	nonsense	1		Pathogenic (1)	0.000000
173.	c.3256T>C	p.W1086R	missense	1	VUS (1)		0.000000
174.	c.2708G>A	p.G903D	missense	1	Likely Pathogenic (1)		0.000000
175.	c.2312T>C	p.V771A	missense	1		VUS (1)	0.000000
176.	c.1457G>A	p.W486X	nonsense	1	Pathogenic (1)		0.000000
177.	c.2939G>A	p.R980H	missense	1		VUS (1)	0.000000
178.	c.1535T>A	p.L512Q	missense	1		VUS favour pathogenic (1)	0.000000
179.	c.1266_1267insTGAT	p.Ile423*	frameshift	1	Pathogenic (1)		0.000000
180.	c.3815-1G>A		essential splice site	1		Pathogenic (1)	0.000000
181.	c.518C>A	p.T173N	missense	1		VUS (1)	0.000000
182.	c.1359del	p.Val454Cysfs*12	frameshift	1	Pathogenic (1)		0.000000
183.	c.3605delG		frameshift	1	Pathogenic (1)		0.000000
184.	c.1950C>G	p.D650E	missense	1		VUS (1)	0.000000
185.	c.3713T>C	p.L1238P	missense	1	Likely Pathogenic (1)		0.000000
186.	c.1174G>T	p.A392S	missense	1	VUS (1)		0.000000
187.	c.1693A>T	p.K565X	nonsense	1		Pathogenic (1)	0.000000
188.	c.2654C>T	p.T885M	missense	1		VUS (1)	0.000022
189.	c.255del	p.Ser86Profs*10	frameshift	1	Pathogenic (1)		0.000000
190.	c.2249C>T	p.T750M	missense	1	Likely Pathogenic (1)		0.000024
191.	c.3452C>T	p.A1151V	missense	1	VUS (1)		0.000078
192.	c.553_562del	p.Lys185Trpfs*12	frameshift	1	Pathogenic (1)		0.000000
193.	c.2504G>T	p.R835L	missense	1	Likely Pathogenic (1)		0.000074
194.	c.3614G>A	p.R1205Q	missense	1	VUS (1)		0.000016
195.	c.3791G>A	p.C1264Y	missense	1		VUS (1)	0.000008
196.	c.2737+1G>C		essential splice site	1		Pathogenic (1)	0.000000
197.	c.1377delC		frameshift	1	Pathogenic (1)		0.000000
198.	c.1591G>C	p.G531R	missense	1		VUS favour pathogenic (1)	0.000017
199.	c.1789C>T	p.R597W	missense	1	VUS (1)		0.000038
200.	c.1575T>G	p.Y525X	nonsense	1		Pathogenic (1)	0.000000
201.	c.1021G>C	p.G341R	missense	1	VUS (1)		0.000000
202.	c.3735delC		frameshift	1		Likely Pathogenic (1)	0.000000
203.	c.3364A>T	p.T1122S	missense	1	Likely Pathogenic (1)		0.000000
204.	c.1678delG	p.Asp560ThrfsX19	frameshift	1		Pathogenic (1)	0.000000
205.	c.799C>G	p.L267V	missense	1	VUS (1)		0.000080
206.	c.3792_3793del	p.Cys1264*	frameshift	1	Likely Pathogenic (1)		0.000000
207.	c.1112C>T	p.P371L	missense	1	VUS (1)		0.000028
208.	c.1224-2A>G		essential splice site	1		Pathogenic (1)	0.000000
209.	c.2149-1G>A		essential splice site	1		Pathogenic (1)	0.000000
210.	c.188G>A	p.R63Q	missense	1	VUS (1)		0.000039
211.	c.821+1G>C		essential splice site	1		Pathogenic (1)	0.000000
212.	c.333_334insT	p.E112X	nonsense	1		Pathogenic (1)	0.000000
213.	c.3297dup	p.Tyr1100Valfs*49	frameshift	1	Pathogenic (1)		0.000000
214.	c.2149_2737del	p.Leu717Alafs*11	frameshift	1	Pathogenic (1)		0.000000
215.	c.2906-2A>G		essential splice site	1		Pathogenic (1)	0.000000
216.	c.3614G>C	p.R1205P	missense	1	Likely Pathogenic (1)		0.000000
217.	c.533delT	p.Val178GlyfsX7	frameshift	1		Pathogenic (1)	0.000000
218.	c.2953A>G	p.K985E	missense	1	Pathogenic (1)		0.000000
219.	c.2524_2525insT	p.Tyr842LeufsX42	frameshift	1		Pathogenic (1)	0.000000
220.	c.2748G>A	p.W916X	nonsense	1	Pathogenic (1)		0.000000
221.	c.932C>T	p.S311L	missense	1		VUS (1)	0.000000
222.	c.2610_2611insC	p.Ser871GlnfsX13	frameshift	1		Pathogenic (1)	0.000000
223.	c.2381C>A	p.P794Q	missense	1	VUS (1)		0.000000
224.	c.1523_1525delinsT	p.Gln508Leufs*22	frameshift	1	Pathogenic (1)		0.000000
225.	c.3065G>A	p.R1022H	missense	1		VUS favour pathogenic (1)	0.000000
226.	c.2603-1G>C		essential splice site	1	Pathogenic (1)		0.000000
227.	c.1960C>T	p.R654C	missense	1		VUS favour benign (1)	0.000008
228.	c.2054_2067+11del	p.Lys685Argfs*3	frameshift	1	Pathogenic (1)		0.000000
229.	c.1021_1028del	p.Gly341*	frameshift	1	Pathogenic (1)		0.000000
230.	c.1418T>C	p.F473S	missense	1		VUS (1)	0.000000
231.	c.1731G>C	p.W577C	missense	1	VUS (1)		0.000000
232.	c.2308+1G>T		essential splice site	1		Pathogenic (1)	0.000000
233.	c.853G>A	p.D285N	missense	1		VUS (1)	0.000000
234.	c.1223+2T>C		essential splice site	1	Pathogenic (1)		0.000000
235.	c.3694A>T	p.K1232X	nonsense	1		Pathogenic (1)	0.000000
236.	c.3281A>T	p.N1094I	missense	1		VUS (1)	0.000000
237.	c.1404del	p.Gln469Serfs*19	frameshift	1	Pathogenic (1)		0.000000
238.	c.1168delC		frameshift	1		Pathogenic (1)	0.000000
239.	c.1672G>A	p.A558T	missense	1		VUS (1)	0.000008
240.	c.3490+1G>A		essential splice site	1	Pathogenic (1)		0.000000
241.	c.655-2del		essential splice site	1	Pathogenic (1)		0.000000
242.	c.2833_2834delCG		frameshift	1		Pathogenic (1)	0.000000
243.	c.121dup	p.Arg41Profs*8	frameshift	1	Pathogenic (1)		0.000000
244.	c.1090+2T>C		essential splice site	1	Pathogenic (1)		0.000000
245.	c.1624+2T>C		essential splice site	1		Pathogenic (1)	0.000000
246.	c.2518G>A	p.V840M	missense	1		VUS (1)	0.000016
247.	c.351_352del	p.Gly118Argfs*8	frameshift	1	Pathogenic (1)		0.000000
248.	c.3413G>C	p.R1138P	missense	1		VUS (1)	0.000000
249.	c.3415G>A	p.V1139I	missense	1		VUS (1)	0.000087
250.	c.1898-1G>A		essential splice site	1	Pathogenic (1)		0.000000
251.	c.2304_2308+2delCATCGGT		essential splice site	1	Pathogenic (1)		0.000000
252.	c.1471G>A	p.V491M	missense	1	VUS (1)		0.000058
253.	c.3083C>G	p.T1028S	missense	1		VUS (1)	0.000000
254.	c.1699_1700delGA	p.Glu567GlyfsX4	frameshift	1		Pathogenic (1)	0.000000
255.	c.1153G>A	p.V385M	missense	1	VUS (1)		0.000010
256.	c.1685C>T	p.A562V	missense	1	VUS (1)		0.000008
257.	c.1343T>C	p.F448S	missense	1		Likely Pathogenic (1)	0.000000
258.	c.1000G>T	p.E334X	nonsense	1		Pathogenic (1)	0.000000
259.	c.2723A>G	p.Y908C	missense	1		VUS (1)	0.000062
260.	c.1924C>T	p.Q642X	nonsense	1		Pathogenic (1)	0.000000
261.	c.*26+2T>C		essential splice site	1	Likely Pathogenic (1)		0.000000
262.	c.2747G>A	p.W916X	nonsense	1		Pathogenic (1)	0.000000
263.	c.3739G>A	p.D1247N	missense	1	VUS (1)		0.000000
264.	c.3043dup	p.Ala1015Glyfs*36	frameshift	1	Pathogenic (1)		0.000000
265.	c.2394_2395insT	p.Gly799TrpfsX34	frameshift	1		Pathogenic (1)	0.000000
266.	c.148A>G	p.S50G	missense	1	VUS (1)		0.000038
267.	c.3166_3167insG	p.Ala1056GlyfsX9	frameshift	1		Pathogenic (1)	0.000000
268.	c.3330+1G>C		essential splice site	1	Pathogenic (1)		0.000000
269.	c.2533C>T	p.R845C	missense	1		VUS favour pathogenic (1)	0.000000
270.	c.2690_2696del	p.Gly897Glufs*25	frameshift	1	Pathogenic (1)		0.000000
271.	c.2965G>T	p.E989X	nonsense	1		Pathogenic (1)	0.000000
272.	c.2188del	p.Thr730Profs*24	frameshift	1	Pathogenic (1)		0.000000
273.	c.2807dup	p.Ala938Glyfs*113	frameshift	1	Pathogenic (1)		0.000000
274.	c.2163delC	p.Glu722ArgfsX32	frameshift	1		Pathogenic (1)	0.000000
275.	c.223G>A	p.D75N	missense	1		VUS favour pathogenic (1)	0.000091
276.	c.2429_2503delins23	p.Arg810Profs*10	frameshift	1	Pathogenic (1)		0.000000
277.	c.3476_3479dupTTAT	p.Pro1161TyrfsX9	frameshift	1		Pathogenic (1)	0.000000
278.	c.3206C>A	p.P1069H	missense	1	Likely Pathogenic (1)		0.000000
279.	c.2247C>A	p.Y749X	nonsense	1	Pathogenic (1)		0.000000
280.	c.2525A>G	p.Y842C	missense	1		VUS (1)	0.000000
281.	c.1455A>T	p.K485N	missense	1	VUS (1)		0.000000
282.	c.2013_2016delinsGG	p.Pro672AspfsX20	frameshift	1		Pathogenic (1)	0.000000
283.	c.713G>A	p.R238H	missense	1		VUS (1)	0.000074
284.	c.1797del	p.His599Glnfs*3	frameshift	1	Pathogenic (1)		0.000000
285.	c.1231A>G	p.I411V	missense	1	VUS (1)		0.000000
286.	c.431_432delGT	p.Gly144AlafsX8	frameshift	1		Pathogenic (1)	0.000000
287.	c.177dup	p.Glu60Argfs*53	frameshift	1	Pathogenic (1)		0.000000
288.	c.1120C>T	p.Q374X	nonsense	1	Pathogenic (1)		0.000000
289.	c.1800delA		frameshift	1		Pathogenic (1)	0.000000
290.	c.391dup	p.Ala131Glyfs*22	frameshift	1	Pathogenic (1)		0.000000
291.	c.566T>A	p.V189D	missense	1		VUS (1)	0.000000
292.	c.1352_1353del	p.Glu451Alafs*23	frameshift	1	Pathogenic (1)		0.000000
293.	c.1397T>A	p.M466K	missense	1		VUS (1)	0.000008
294.	c.731del	p.Lys244Argfs*56	frameshift	1	Pathogenic (1)		0.000000
295.	c.2436G>T	p.K812N	missense	1		VUS (1)	0.000000
296.	c.2503C>T	p.R835C	missense	1	VUS (1)		0.000024
297.	c.1A>T	p.Met1?	missense	1	Likely Pathogenic (1)		0.000000
298.	c.2828G>A	p.R943Q	missense	1		VUS (1)	0.000025
299.	c.241G>T	p.V81F	missense	1	VUS (1)		0.000000
300.	c.2198G>A	p.R733H	missense	1	VUS (1)		0.000034
301.	c.3316G>A	p.D1106N	missense	1	VUS (1)		0.000061
302.	c.3825A>G	p.X1275TrpextX77	nonsense	1		Likely Pathogenic (1)	0.000000
303.	c.994G>A	p.E332K	missense	1	VUS (1)		0.000009
304.	c.451G>A	p.D151N	missense	1		VUS (1)	0.000041
305.	c.2265C>A	p.N755K	missense	1	Pathogenic (1)		0.000000
306.	c.1303C>T	p.Q435X	nonsense	1	Pathogenic (1)		0.000000
307.	c.104G>A	p.R35Q	missense	1		VUS (1)	0.000079
308.	c.187C>T	p.R63W	missense	1	VUS (1)		0.000077
309.	c.3476_3477delTT		frameshift	1		Pathogenic (1)	0.000000
310.	c.3797G>A	p.C1266Y	missense	1		Likely Pathogenic (1)	0.000000
311.	c.3357C>A	p.Y1119X	nonsense	1	Pathogenic (1)		0.000000
312.	c.743_746delACTG		frameshift	1	Pathogenic (1)		0.000000
313.	c.2780_2781delCA		frameshift	1		Pathogenic (1)	0.000000
314.	c.1458-1G>A		essential splice site	1		Pathogenic (1)	0.000000
315.	c.551_552insT	p.Lys185GlufsX56	frameshift	1		Pathogenic (1)	0.000000
316.	c.2541C>A	p.Y847X	nonsense	1		Pathogenic (1)	0.000000
317.	c.2234A>G	p.D745G	missense	1		VUS (1)	0.000000
318.	c.3331-1G>A		essential splice site	1		Pathogenic (1)	0.000000
319.	c.3580G>A	p.A1194T	missense	1		VUS (1)	0.000008
320.	c.1586C>G	p.T529S	missense	1		VUS favour pathogenic (1)	0.000000
321.	c.3335G>A	p.W1112X	nonsense	1		Pathogenic (1)	0.000000
322.	c.2718_2719dup	p.Glu907Glyfs*18	frameshift	1	Pathogenic (1)		0.000000
323.	c.481C>A	p.P161T	missense	1		VUS favour pathogenic (1)	0.000041
324.	c.966G>A	p.W322X	nonsense	1		Pathogenic (1)	0.000000
325.	c.2065C>T	p.Q689X	nonsense	1	Pathogenic (1)		0.000000
326.	c.1505G>T	p.R502L	missense	1		VUS favour pathogenic (1)	0.000000
327.	c.2371C>T	p.Q791X	nonsense	1	Pathogenic (1)		0.000000
328.	c.1458G>A	p.W486X	nonsense	1	Pathogenic (1)		0.000000
329.	c.3548T>G	p.F1183C	missense	1		Likely Pathogenic (1)	0.000000
330.	c.2584C>T	p.Q862X	nonsense	1	Pathogenic (1)		0.000000
331.	c.1358C>T	p.P453L	missense	1		VUS (1)	0.000008
332.	c.821+2T>G		essential splice site	1	Pathogenic (1)		0.000000
333.	c.1569dup	p.His524Alafs*7	frameshift	1	Pathogenic (1)		0.000000
334.	c.1201C>T	p.Q401X	nonsense	1	Pathogenic (1)		0.000000
335.	c.2517_2538del	p.Val840ThrfsX32	frameshift	1		Pathogenic (1)	0.000000
336.	c.1376_1377del	p.Pro459Leufs*15	frameshift	1	Pathogenic (1)		0.000000
337.	c.2995-1G>A		essential splice site	1	Pathogenic (1)		0.000000
338.	c.256_258del	p.Ser86del	inframe	1	VUS (1)		0.000000
339.	c.611_618delinsT	p.Gly204Valfs*94	frameshift	1	Pathogenic (1)		0.000000
340.	c.100_110dup	p.Val38Serfs*5	frameshift	1	Pathogenic (1)		0.000000
341.	c.3617delG		frameshift	1	Pathogenic (1)		0.000000
342.	c.2560A>G	p.M854V	missense	1		VUS (1)	0.000000
343.	c.2905+1G>C		essential splice site	1		Pathogenic (1)	0.000000
344.	c.1433C>T	p.S478L	missense	1	Likely Pathogenic (1)		0.000017
345.	c.3098G>A	p.R1033Q	missense	1		VUS (1)	0.000000
346.	c.655-1G>A		essential splice site	1		Pathogenic (1)	0.000000
347.	c.2993A>G	p.Q998R	missense	1		VUS favour pathogenic (1)	0.000000
348.	c.1072G>A	p.D358N	missense	1	VUS (1)		0.000008
349.	c.3746G>T	p.G1249V	missense	1		VUS (1)	0.000000
350.	c.3776delA		frameshift	1		Pathogenic (1)	0.000000
351.	c.3068_3069insA	p.Asn1023LysfsX28	frameshift	1		Pathogenic (1)	0.000000
352.	c.2113_2114insA	p.Thr705AsnfsX3	frameshift	1		Pathogenic (1)	0.000000
353.	c.506-1G>A		essential splice site	1	Pathogenic (1)		0.000000
354.	c.2671C>T	p.R891W	missense	1		Likely Pathogenic (1)	0.000031
355.	c.1351+2T>C		essential splice site	1		Pathogenic (1)	0.000000
356.	c.811_817delTTCCGCC		frameshift	1	Pathogenic (1)		0.000000
357.	c.2641G>A	p.V881I	missense	1		VUS (1)	0.000018
358.	c.2738-2A>G		essential splice site	1	Pathogenic (1)		0.000000
359.	c.2875_2876delAC	p.Thr959GlyfsX91	frameshift	1		Pathogenic (1)	0.000000
360.	c.3728C>G	p.P1243R	missense	1	VUS (1)		0.000000
361.	c.3690_3691delCA	p.Phe1230LeufsX11	frameshift	1		Pathogenic (1)	0.000000
362.	c.1892delT		frameshift	1		Pathogenic (1)	0.000000
363.	c.2968C>G	p.P990A	missense	1	Likely Pathogenic (1)		0.000000
364.	c.2437A>T	p.K813X	nonsense	1		Pathogenic (1)	0.000000
365.	c.49C>T	p.R17W	missense	1	VUS (1)		0.000023
366.	c.3753T>G	p.Y1251X	nonsense	1		Pathogenic (1)	0.000000
367.	c.3316del	p.Asp1106Thrfs*83	frameshift	1	Pathogenic (1)		0.000000
368.	c.2528_2536delAGATGCGCG	p.Glu843_Arg845del	inframe	1		Pathogenic (1)	0.000000
369.	c.2502del	p.Arg835Alafs*2	frameshift	1	Pathogenic (1)		0.000000
370.	c.290C>T	p.A97V	missense	1		VUS favour pathogenic (1)	0.000000
371.	c.2603-2_2603-1delinsGA		essential splice site	1	Pathogenic (1)		0.000000
372.	c.2161_2168del	p.Thr721Profs*23	frameshift	1	Pathogenic (1)		0.000000
373.	c.993_994insT	p.E332X	nonsense	1		Pathogenic (1)	0.000000
374.	c.2789del	p.Leu930Argfs*2	frameshift	1	Pathogenic (1)		0.000000
375.	c.3742G>A	p.G1248R	missense	1		VUS (1)	0.000033
376.	c.436A>C	p.T146P	missense	1		VUS (1)	0.000000
377.	c.1224-1G>T		essential splice site	1	Pathogenic (1)		0.000000
378.	c.506-1G>T		essential splice site	1		Pathogenic (1)	0.000000
379.	c.326C>T	p.A109V	missense	1		VUS (1)	0.000000
380.	c.1405C>T	p.Q469X	nonsense	1	Pathogenic (1)		0.000000
381.	c.2040_2041insT	p.Val681CysfsX12	frameshift	1		Pathogenic (1)	0.000000
382.	c.103C>T	p.R35W	missense	1		VUS (1)	0.000056
383.	c.1080G>C	p.K360N	missense	1	VUS (1)		0.000000
384.	c.1188G>T	p.W396C	missense	1		VUS (1)	0.000000
385.	c.1756C>G	p.P586A	missense	1	Likely Pathogenic (1)		0.000000
386.	c.3656T>C	p.L1219P	missense	1	VUS (1)		0.000000
387.	c.1097A>C	p.Q366P	missense	1	VUS (1)		0.000000
388.	c.2048G>A	p.W683X	nonsense	1		Pathogenic (1)	0.000000
389.	c.3019T>C	p.W1007R	missense	1	VUS (1)		0.000000
390.	c.365C>A	p.A122D	missense	1	VUS (1)		0.000000
391.	c.931T>A	p.S311T	missense	1		VUS (1)	0.000000
392.	c.1540A>G	p.I514V	missense	1		VUS (1)	0.000008
393.	c.3572C>T	p.S1191L	missense	1	VUS (1)		0.000016
394.	c.701C>A	p.T234N	missense	1	Likely Pathogenic (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.