MYBPC3 protein-altering 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.1483C>G	p.R495G	missense	14	Likely Pathogenic (10)	Likely Pathogenic (4)	0.000000
13.	c.1484G>A	p.R495Q	missense	14	Likely Pathogenic (4)	VUS favour pathogenic (10)	0.000008
14.	c.3697C>T	p.Q1233X	nonsense	13	Likely Pathogenic (4)	Pathogenic (9)	0.000008
15.	c.2308G>A	p.D770N	missense	11	Likely Pathogenic (5)	Likely Pathogenic (6)	0.000008
16.	c.3330+2T>G		essential splice site	11		Pathogenic (11)	0.000000
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.2459G>A	p.R820Q	missense	6	VUS (5)	Likely Pathogenic (1)	0.000016
32.	c.2573G>A	p.S858N	missense	6	Likely Pathogenic (2)	VUS favour pathogenic (4)	0.000000
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.2556_2557delinsTCT	p.Gly853fs	frameshift	5	Pathogenic (4)	Pathogenic (1)	0.000000
36.	c.2610delC		frameshift	5	Pathogenic (5)		0.000000
37.	c.913_914delTT		frameshift	5		Pathogenic (5)	0.000000
38.	c.821+2T>C		essential splice site	5	Pathogenic (4)	Pathogenic (1)	0.000000
39.	c.2905C>T	p.Q969X	nonsense	5	Pathogenic (2)	Pathogenic (3)	0.000000
40.	c.821+1G>A		essential splice site	5	Pathogenic (1)	Pathogenic (4)	0.000043
41.	c.2374T>C	p.W792R	missense	5		Likely Pathogenic (5)	0.000000
42.	c.3064C>T	p.R1022C	missense	5	VUS (1)	VUS favour pathogenic (4)	0.000008
43.	c.3286G>T	p.E1096X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000000
44.	c.3277G>T	p.G1093C	missense	4	VUS (3)	VUS (1)	0.000020
45.	c.1483C>T	p.R495W	missense	4	Likely Pathogenic (2)	VUS favour pathogenic (2)	0.000000
46.	c.2210C>T	p.T737M	missense	4	VUS (3)	VUS (1)	0.000050
47.	c.3408C>A	p.Y1136X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000000
48.	c.3763G>A	p.A1255T	missense	4	VUS (3)	VUS favour pathogenic (1)	0.000075
49.	c.3163A>T	p.K1055X	nonsense	4	Pathogenic (4)		0.000000
50.	c.2182G>T	p.E728X	nonsense	4		Pathogenic (4)	0.000000
51.	c.3181C>T	p.Q1061X	nonsense	4	Pathogenic (3)	Pathogenic (1)	0.000016
52.	c.484C>T	p.Q162X	nonsense	4	Pathogenic (4)		0.000000
53.	c.3798C>G	p.C1266W	missense	4	VUS (4)		0.000000
54.	c.26-2A>G		essential splice site	4		Pathogenic (4)	0.000051
55.	c.2873C>T	p.T958I	missense	4	VUS (1)	VUS favour benign (3)	0.000065
56.	c.3742_3759dup	p.Gly1248_Cys1253dup	inframe	4		Likely Pathogenic (4)	0.000000
57.	c.1591G>A	p.G531R	missense	4	Likely Pathogenic (1)	VUS favour pathogenic (3)	0.000017
58.	c.2454G>A	p.W818X	nonsense	4		Pathogenic (4)	0.000000
59.	c.3190+1G>A		essential splice site	3		Pathogenic (3)	0.000000
60.	c.1790G>A	p.R597Q	missense	3	VUS (1)	VUS favour pathogenic (2)	0.000000
61.	c.3600_3609delCTGCTGTGCT		frameshift	3	Pathogenic (3)	Pathogenic (0)	0.000000
62.	c.833delG	p.Gly278GlufsX22	frameshift	3	Pathogenic (2)	Pathogenic (1)	0.000000
63.	c.2450G>A	p.R817Q	missense	3		VUS favour pathogenic (3)	0.000016
64.	c.2558delG		frameshift	3	Pathogenic (1)	Pathogenic (2)	0.000000
65.	c.1037G>A	p.R346H	missense	3	VUS (1)	VUS (2)	0.000000
66.	c.3233G>A	p.W1078X	nonsense	3		Pathogenic (3)	0.000022
67.	c.772+1G>A		essential splice site	3	Pathogenic (1)	Pathogenic (2)	0.000000
68.	c.177_187del	p.Glu60AlafsX49	frameshift	3	Pathogenic (2)	Pathogenic (1)	0.000000
69.	c.2920C>T	p.Q974X	nonsense	3		Pathogenic (3)	0.000000
70.	c.532G>A	p.V178M	missense	3	VUS (1)	VUS favour pathogenic (2)	0.000020
71.	c.3624delC		frameshift	3	Pathogenic (1)	Pathogenic (2)	0.000000
72.	c.355G>A	p.E119K	missense	3		VUS (3)	0.000000
73.	c.2308+1G>A		essential splice site	3	Pathogenic (2)	Pathogenic (1)	0.000000
74.	c.1123G>A	p.V375M	missense	3	VUS (3)		0.000009
75.	c.3491-2A>T		essential splice site	3		Pathogenic (3)	0.000000
76.	c.1828G>C	p.D610H	missense	3	VUS (1)	VUS favour benign (2)	0.000058
77.	c.1720C>T	p.R574W	missense	3	VUS (3)		0.000054
78.	c.3129C>A	p.Y1043X	nonsense	3	Pathogenic (3)		0.000000
79.	c.2311_2312insG	p.Val771GlyfsX62	frameshift	3		Pathogenic (3)	0.000000
80.	c.2309-1G>A		essential splice site	3	Pathogenic (3)		0.000000
81.	c.3767_3769delCCA	p.Thr1256del	inframe	3		Likely Pathogenic (3)	0.000000
82.	c.2545del	p.Val849Serfs*30	frameshift	3	Pathogenic (3)		0.000000
83.	c.25+1G>A		essential splice site	2	Pathogenic (2)		0.000000
84.	c.3192_3193insC	p.Lys1065GlnfsX12	frameshift	2		Pathogenic (2)	0.000000
85.	c.1090+1G>A		essential splice site	2	Pathogenic (1)	Pathogenic (1)	0.000000
86.	c.2943_2947delGACCA		frameshift	2		Pathogenic (2)	0.000000
87.	c.999C>G	p.Y333X	nonsense	2		Pathogenic (2)	0.000000
88.	c.3624_3625insC	p.Lys1209GlnfsX33	frameshift	2		Pathogenic (2)	0.000000
89.	c.1766G>A	p.R589H	missense	2		VUS (2)	0.000000
90.	c.3627+1G>T		essential splice site	2	Pathogenic (2)		0.000000
91.	c.3005G>A	p.R1002Q	missense	2	VUS (2)		0.000046
92.	c.373G>T	p.A125S	missense	2	VUS (1)	VUS (1)	0.000000
93.	c.818G>A	p.R273H	missense	2	VUS (2)		0.000042
94.	c.844C>T	p.R282W	missense	2	Likely Pathogenic (1)	VUS favour pathogenic (1)	0.000000
95.	c.1999_2000delinsG	p.Leu667AspfsX15	frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
96.	c.557C>T	p.P186L	missense	2	VUS (2)		0.000047
97.	c.1895delT	p.Met632ArgfsX31	frameshift	2		Pathogenic (2)	0.000000
98.	c.1038_1042dupCGGCA		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000008
99.	c.2882C>T	p.P961L	missense	2		VUS (2)	0.000048
100.	c.459delC		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
101.	c.3582_3593delGGGCTACACTGC		inframe	2	Likely Pathogenic (1)		0.000000
102.	c.2197C>T	p.R733C	missense	2	Likely Pathogenic (1)	VUS (1)	0.000085
103.	c.2269G>A	p.V757M	missense	2	VUS (1)	VUS (1)	0.000066
104.	c.3752A>G	p.Y1251C	missense	2	VUS (2)		0.000000
105.	c.3455_3466del	p.Ala1152_Lys1155del	inframe	2	Likely Pathogenic (2)		0.000000
106.	c.2905+2dup		essential splice site	2	Likely Pathogenic (2)		0.000000
107.	c.2524dup	p.Tyr842Leufs*42	frameshift	2	Pathogenic (2)		0.000000
108.	c.1210C>T	p.Q404X	nonsense	2		Pathogenic (2)	0.000000
109.	c.3271del	p.Asp1091Metfs*98	frameshift	2	Pathogenic (2)		0.000000
110.	c.932C>A	p.S311X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
111.	c.436_437insA	p.Thr146AsnfsX7	frameshift	2		Pathogenic (2)	0.000000
112.	c.1869C>A	p.C623X	nonsense	2		Pathogenic (2)	0.000000
113.	c.814C>T	p.R272C	missense	2		VUS (2)	0.000083
114.	c.1934C>T	p.P645L	missense	2		VUS (2)	0.000000
115.	c.2526C>G	p.Y842X	nonsense	2	Pathogenic (2)		0.000000
116.	c.3470C>T	p.P1157L	missense	2	VUS (2)		0.000093
117.	c.2320G>A	p.A774T	missense	2		VUS (2)	0.000000
118.	c.2300A>G	p.K767R	missense	2	VUS (2)		0.000016
119.	c.1513_1515delAAG		inframe	2		VUS favour pathogenic (2)	0.000000
120.	c.1273C>T	p.Q425X	nonsense	2	Pathogenic (1)	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.3253G>T	p.E1085X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
124.	c.1897+1G>A		essential splice site	2		Pathogenic (2)	0.000000
125.	c.1456T>G	p.W486G	missense	2	VUS (1)	Likely Pathogenic (1)	0.000000
126.	c.1351+1G>A		essential splice site	2	Pathogenic (1)	Pathogenic (1)	0.000000
127.	c.1021G>A	p.G341S	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000025
128.	c.2219G>C	p.G740A	missense	2	VUS (2)		0.000000
129.	c.126G>A	p.W42X	nonsense	2	Pathogenic (2)		0.000000
130.	c.3373G>A	p.V1125M	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000022
131.	c.3676C>T	p.R1226C	missense	2	VUS (1)	VUS (1)	0.000058
132.	c.2432A>G	p.K811R	missense	2	VUS (2)		0.000000
133.	c.2534_2538delGCGTC		frameshift	2	Pathogenic (1)	Pathogenic (1)	0.000000
134.	c.1357_1358delCC		frameshift	2		Pathogenic (2)	0.000000
135.	c.1863delC	p.Phe621LeufsX42	frameshift	2		Pathogenic (2)	0.000000
136.	c.3751T>C	p.Y1251H	missense	2	VUS (2)		0.000000
137.	c.3811C>T	p.R1271X	nonsense	2	VUS (1)	Pathogenic (1)	0.000025
138.	c.1213A>G	p.M405V	missense	2	VUS (1)	Pathogenic (1)	0.000000
139.	c.1841A>G	p.Y614C	missense	2	VUS (1)	VUS favour pathogenic (1)	0.000000
140.	c.2953A>T	p.K985X	nonsense	2	Pathogenic (1)	Pathogenic (1)	0.000000
141.	c.2449C>T	p.R817W	missense	2	VUS (1)	VUS (1)	0.000000
142.	c.1886T>C	p.L629P	missense	2	VUS (2)		0.000000
143.	c.747C>A	p.C249X	nonsense	2	Pathogenic (2)		0.000000
144.	c.443dup	p.Ala149Serfs*4	frameshift	2	Pathogenic (2)		0.000000
145.	c.2249C>T	p.T750M	missense	1	Likely Pathogenic (1)		0.000024
146.	c.3452C>T	p.A1151V	missense	1	VUS (1)		0.000078
147.	c.553_562del	p.Lys185Trpfs*12	frameshift	1	Pathogenic (1)		0.000000
148.	c.2504G>T	p.R835L	missense	1	Likely Pathogenic (1)		0.000074
149.	c.103C>T	p.R35W	missense	1		VUS (1)	0.000056
150.	c.3614G>A	p.R1205Q	missense	1	VUS (1)		0.000016
151.	c.2654C>T	p.T885M	missense	1		VUS (1)	0.000022
152.	c.255del	p.Ser86Profs*10	frameshift	1	Pathogenic (1)		0.000000
153.	c.2048G>A	p.W683X	nonsense	1		Pathogenic (1)	0.000000
154.	c.1789C>T	p.R597W	missense	1	VUS (1)		0.000038
155.	c.1021G>C	p.G341R	missense	1	VUS (1)		0.000000
156.	c.3791G>A	p.C1264Y	missense	1		VUS (1)	0.000008
157.	c.2737+1G>C		essential splice site	1		Pathogenic (1)	0.000000
158.	c.1377delC		frameshift	1	Pathogenic (1)		0.000000
159.	c.1112C>T	p.P371L	missense	1	VUS (1)		0.000028
160.	c.2149-1G>A		essential splice site	1		Pathogenic (1)	0.000000
161.	c.188G>A	p.R63Q	missense	1	VUS (1)		0.000039
162.	c.821+1G>C		essential splice site	1		Pathogenic (1)	0.000000
163.	c.3364A>T	p.T1122S	missense	1	Likely Pathogenic (1)		0.000000
164.	c.3288delG		frameshift	1		Pathogenic (1)	0.000000
165.	c.1678delG	p.Asp560ThrfsX19	frameshift	1		Pathogenic (1)	0.000000
166.	c.799C>G	p.L267V	missense	1	VUS (1)		0.000080
167.	c.3792_3793del	p.Cys1264*	frameshift	1	Likely Pathogenic (1)		0.000000
168.	c.2149_2737del	p.Leu717Alafs*11	frameshift	1	Pathogenic (1)		0.000000
169.	c.2906-2A>G		essential splice site	1		Pathogenic (1)	0.000000
170.	c.3614G>C	p.R1205P	missense	1	Likely Pathogenic (1)		0.000000
171.	c.533delT	p.Val178GlyfsX7	frameshift	1		Pathogenic (1)	0.000000
172.	c.2953A>G	p.K985E	missense	1	Pathogenic (1)		0.000000
173.	c.2524_2525insT	p.Tyr842LeufsX42	frameshift	1		Pathogenic (1)	0.000000
174.	c.1156G>T	p.E386X	nonsense	1		Pathogenic (1)	0.000000
175.	c.333_334insT	p.E112X	nonsense	1		Pathogenic (1)	0.000000
176.	c.3297dup	p.Tyr1100Valfs*49	frameshift	1	Pathogenic (1)		0.000000
177.	c.1523_1525delinsT	p.Gln508Leufs*22	frameshift	1	Pathogenic (1)		0.000000
178.	c.3065G>A	p.R1022H	missense	1		VUS favour pathogenic (1)	0.000000
179.	c.2603-1G>C		essential splice site	1	Pathogenic (1)		0.000000
180.	c.2054_2067+11del	p.Lys685Argfs*3	frameshift	1	Pathogenic (1)		0.000000
181.	c.2748G>A	p.W916X	nonsense	1	Pathogenic (1)		0.000000
182.	c.2610_2611insC	p.Ser871GlnfsX13	frameshift	1		Pathogenic (1)	0.000000
183.	c.2381C>A	p.P794Q	missense	1	VUS (1)		0.000000
184.	c.1628delA		frameshift	1		Pathogenic (1)	0.000000
185.	c.3281A>T	p.N1094I	missense	1		VUS (1)	0.000000
186.	c.1404del	p.Gln469Serfs*19	frameshift	1	Pathogenic (1)		0.000000
187.	c.1778C>T	p.S593F	missense	1		VUS favour pathogenic (1)	0.000034
188.	c.1021_1028del	p.Gly341*	frameshift	1	Pathogenic (1)		0.000000
189.	c.1418T>C	p.F473S	missense	1		VUS (1)	0.000000
190.	c.1731G>C	p.W577C	missense	1	VUS (1)		0.000000
191.	c.853G>A	p.D285N	missense	1		VUS (1)	0.000000
192.	c.1223+2T>C		essential splice site	1	Pathogenic (1)		0.000000
193.	c.3694A>T	p.K1232X	nonsense	1		Pathogenic (1)	0.000000
194.	c.1090+2T>C		essential splice site	1	Pathogenic (1)		0.000000
195.	c.2518G>A	p.V840M	missense	1		VUS (1)	0.000016
196.	c.351_352del	p.Gly118Argfs*8	frameshift	1	Pathogenic (1)		0.000000
197.	c.3413G>C	p.R1138P	missense	1		VUS (1)	0.000000
198.	c.1672G>A	p.A558T	missense	1		VUS (1)	0.000008
199.	c.3490+1G>A		essential splice site	1	Pathogenic (1)		0.000000
200.	c.655-2del		essential splice site	1	Pathogenic (1)		0.000000
201.	c.2312T>C	p.V771A	missense	1		VUS (1)	0.000000
202.	c.121dup	p.Arg41Profs*8	frameshift	1	Pathogenic (1)		0.000000
203.	c.2304_2308+2delCATCGGT		essential splice site	1	Pathogenic (1)		0.000000
204.	c.1471G>A	p.V491M	missense	1	VUS (1)		0.000058
205.	c.3083C>G	p.T1028S	missense	1		VUS (1)	0.000000
206.	c.3415G>A	p.V1139I	missense	1		VUS (1)	0.000087
207.	c.1898-1G>A		essential splice site	1	Pathogenic (1)		0.000000
208.	c.2308+1G>T		essential splice site	1		Pathogenic (1)	0.000000
209.	c.1000G>T	p.E334X	nonsense	1		Pathogenic (1)	0.000000
210.	c.2723A>G	p.Y908C	missense	1		VUS (1)	0.000062
211.	c.2833_2834delCG		frameshift	1		Pathogenic (1)	0.000000
212.	c.*26+2T>C		essential splice site	1	Likely Pathogenic (1)		0.000000
213.	c.1699_1700delGA	p.Glu567GlyfsX4	frameshift	1		Pathogenic (1)	0.000000
214.	c.1153G>A	p.V385M	missense	1	VUS (1)		0.000010
215.	c.1693A>T	p.K565X	nonsense	1		Pathogenic (1)	0.000000
216.	c.1685C>T	p.A562V	missense	1	VUS (1)		0.000008
217.	c.3166_3167insG	p.Ala1056GlyfsX9	frameshift	1		Pathogenic (1)	0.000000
218.	c.3330+1G>C		essential splice site	1	Pathogenic (1)		0.000000
219.	c.1591G>C	p.G531R	missense	1		VUS favour pathogenic (1)	0.000017
220.	c.1575T>G	p.Y525X	nonsense	1		Pathogenic (1)	0.000000
221.	c.2747G>A	p.W916X	nonsense	1		Pathogenic (1)	0.000000
222.	c.3739G>A	p.D1247N	missense	1	VUS (1)		0.000000
223.	c.3043dup	p.Ala1015Glyfs*36	frameshift	1	Pathogenic (1)		0.000000
224.	c.2394_2395insT	p.Gly799TrpfsX34	frameshift	1		Pathogenic (1)	0.000000
225.	c.148A>G	p.S50G	missense	1	VUS (1)		0.000038
226.	c.2807dup	p.Ala938Glyfs*113	frameshift	1	Pathogenic (1)		0.000000
227.	c.2163delC	p.Glu722ArgfsX32	frameshift	1		Pathogenic (1)	0.000000
228.	c.2429_2503delins23	p.Arg810Profs*10	frameshift	1	Pathogenic (1)		0.000000
229.	c.1224-2A>G		essential splice site	1		Pathogenic (1)	0.000000
230.	c.3476_3479dupTTAT	p.Pro1161TyrfsX9	frameshift	1		Pathogenic (1)	0.000000
231.	c.3206C>A	p.P1069H	missense	1	Likely Pathogenic (1)		0.000000
232.	c.2533C>T	p.R845C	missense	1		VUS favour pathogenic (1)	0.000000
233.	c.2690_2696del	p.Gly897Glufs*25	frameshift	1	Pathogenic (1)		0.000000
234.	c.3735delC		frameshift	1		Likely Pathogenic (1)	0.000000
235.	c.2965G>T	p.E989X	nonsense	1		Pathogenic (1)	0.000000
236.	c.2188del	p.Thr730Profs*24	frameshift	1	Pathogenic (1)		0.000000
237.	c.1797del	p.His599Glnfs*3	frameshift	1	Pathogenic (1)		0.000000
238.	c.1231A>G	p.I411V	missense	1	VUS (1)		0.000000
239.	c.431_432delGT	p.Gly144AlafsX8	frameshift	1		Pathogenic (1)	0.000000
240.	c.2247C>A	p.Y749X	nonsense	1	Pathogenic (1)		0.000000
241.	c.2525A>G	p.Y842C	missense	1		VUS (1)	0.000000
242.	c.1455A>T	p.K485N	missense	1	VUS (1)		0.000000
243.	c.2013_2016delinsGG	p.Pro672AspfsX20	frameshift	1		Pathogenic (1)	0.000000
244.	c.1397T>A	p.M466K	missense	1		VUS (1)	0.000008
245.	c.731del	p.Lys244Argfs*56	frameshift	1	Pathogenic (1)		0.000000
246.	c.2436G>T	p.K812N	missense	1		VUS (1)	0.000000
247.	c.177dup	p.Glu60Argfs*53	frameshift	1	Pathogenic (1)		0.000000
248.	c.1120C>T	p.Q374X	nonsense	1	Pathogenic (1)		0.000000
249.	c.1960C>T	p.R654C	missense	1		VUS favour benign (1)	0.000008
250.	c.391dup	p.Ala131Glyfs*22	frameshift	1	Pathogenic (1)		0.000000
251.	c.932C>T	p.S311L	missense	1		VUS (1)	0.000000
252.	c.566T>A	p.V189D	missense	1		VUS (1)	0.000000
253.	c.1352_1353del	p.Glu451Alafs*23	frameshift	1	Pathogenic (1)		0.000000
254.	c.241G>T	p.V81F	missense	1	VUS (1)		0.000000
255.	c.2198G>A	p.R733H	missense	1	VUS (1)		0.000034
256.	c.3316G>A	p.D1106N	missense	1	VUS (1)		0.000061
257.	c.2503C>T	p.R835C	missense	1	VUS (1)		0.000024
258.	c.1A>T	p.Met1?	missense	1	Likely Pathogenic (1)		0.000000
259.	c.2828G>A	p.R943Q	missense	1		VUS (1)	0.000025
260.	c.1303C>T	p.Q435X	nonsense	1	Pathogenic (1)		0.000000
261.	c.1624+2T>C		essential splice site	1		Pathogenic (1)	0.000000
262.	c.104G>A	p.R35Q	missense	1		VUS (1)	0.000079
263.	c.3825A>G	p.X1275TrpextX77	nonsense	1		Likely Pathogenic (1)	0.000000
264.	c.994G>A	p.E332K	missense	1	VUS (1)		0.000009
265.	c.1168delC		frameshift	1		Pathogenic (1)	0.000000
266.	c.451G>A	p.D151N	missense	1		VUS (1)	0.000041
267.	c.2265C>A	p.N755K	missense	1	Pathogenic (1)		0.000000
268.	c.1458-1G>A		essential splice site	1		Pathogenic (1)	0.000000
269.	c.187C>T	p.R63W	missense	1	VUS (1)		0.000077
270.	c.3357C>A	p.Y1119X	nonsense	1	Pathogenic (1)		0.000000
271.	c.743_746delACTG		frameshift	1	Pathogenic (1)		0.000000
272.	c.1586C>G	p.T529S	missense	1		VUS favour pathogenic (1)	0.000000
273.	c.2718_2719dup	p.Glu907Glyfs*18	frameshift	1	Pathogenic (1)		0.000000
274.	c.1343T>C	p.F448S	missense	1		Likely Pathogenic (1)	0.000000
275.	c.1924C>T	p.Q642X	nonsense	1		Pathogenic (1)	0.000000
276.	c.551_552insT	p.Lys185GlufsX56	frameshift	1		Pathogenic (1)	0.000000
277.	c.2541C>A	p.Y847X	nonsense	1		Pathogenic (1)	0.000000
278.	c.3331-1G>A		essential splice site	1		Pathogenic (1)	0.000000
279.	c.2371C>T	p.Q791X	nonsense	1	Pathogenic (1)		0.000000
280.	c.1458G>A	p.W486X	nonsense	1	Pathogenic (1)		0.000000
281.	c.3548T>G	p.F1183C	missense	1		Likely Pathogenic (1)	0.000000
282.	c.2584C>T	p.Q862X	nonsense	1	Pathogenic (1)		0.000000
283.	c.966G>A	p.W322X	nonsense	1		Pathogenic (1)	0.000000
284.	c.2065C>T	p.Q689X	nonsense	1	Pathogenic (1)		0.000000
285.	c.1505G>T	p.R502L	missense	1		VUS favour pathogenic (1)	0.000000
286.	c.1201C>T	p.Q401X	nonsense	1	Pathogenic (1)		0.000000
287.	c.2517_2538del	p.Val840ThrfsX32	frameshift	1		Pathogenic (1)	0.000000
288.	c.1376_1377del	p.Pro459Leufs*15	frameshift	1	Pathogenic (1)		0.000000
289.	c.223G>A	p.D75N	missense	1		VUS favour pathogenic (1)	0.000091
290.	c.821+2T>G		essential splice site	1	Pathogenic (1)		0.000000
291.	c.1569dup	p.His524Alafs*7	frameshift	1	Pathogenic (1)		0.000000
292.	c.100_110dup	p.Val38Serfs*5	frameshift	1	Pathogenic (1)		0.000000
293.	c.713G>A	p.R238H	missense	1		VUS (1)	0.000074
294.	c.3617delG		frameshift	1	Pathogenic (1)		0.000000
295.	c.2560A>G	p.M854V	missense	1		VUS (1)	0.000000
296.	c.2995-1G>A		essential splice site	1	Pathogenic (1)		0.000000
297.	c.256_258del	p.Ser86del	inframe	1	VUS (1)		0.000000
298.	c.611_618delinsT	p.Gly204Valfs*94	frameshift	1	Pathogenic (1)		0.000000
299.	c.1072G>A	p.D358N	missense	1	VUS (1)		0.000008
300.	c.3746G>T	p.G1249V	missense	1		VUS (1)	0.000000
301.	c.2905+1G>C		essential splice site	1		Pathogenic (1)	0.000000
302.	c.1433C>T	p.S478L	missense	1	Likely Pathogenic (1)		0.000017
303.	c.3098G>A	p.R1033Q	missense	1		VUS (1)	0.000000
304.	c.1800delA		frameshift	1		Pathogenic (1)	0.000000
305.	c.2113_2114insA	p.Thr705AsnfsX3	frameshift	1		Pathogenic (1)	0.000000
306.	c.506-1G>A		essential splice site	1	Pathogenic (1)		0.000000
307.	c.1351+2T>C		essential splice site	1		Pathogenic (1)	0.000000
308.	c.811_817delTTCCGCC		frameshift	1	Pathogenic (1)		0.000000
309.	c.3068_3069insA	p.Asn1023LysfsX28	frameshift	1		Pathogenic (1)	0.000000
310.	c.3690_3691delCA	p.Phe1230LeufsX11	frameshift	1		Pathogenic (1)	0.000000
311.	c.2968C>G	p.P990A	missense	1	Likely Pathogenic (1)		0.000000
312.	c.2437A>T	p.K813X	nonsense	1		Pathogenic (1)	0.000000
313.	c.49C>T	p.R17W	missense	1	VUS (1)		0.000023
314.	c.3316del	p.Asp1106Thrfs*83	frameshift	1	Pathogenic (1)		0.000000
315.	c.2738-2A>G		essential splice site	1	Pathogenic (1)		0.000000
316.	c.2875_2876delAC	p.Thr959GlyfsX91	frameshift	1		Pathogenic (1)	0.000000
317.	c.3728C>G	p.P1243R	missense	1	VUS (1)		0.000000
318.	c.2161_2168del	p.Thr721Profs*23	frameshift	1	Pathogenic (1)		0.000000
319.	c.2780_2781delCA		frameshift	1		Pathogenic (1)	0.000000
320.	c.993_994insT	p.E332X	nonsense	1		Pathogenic (1)	0.000000
321.	c.2789del	p.Leu930Argfs*2	frameshift	1	Pathogenic (1)		0.000000
322.	c.2528_2536delAGATGCGCG	p.Glu843_Arg845del	inframe	1		Pathogenic (1)	0.000000
323.	c.2502del	p.Arg835Alafs*2	frameshift	1	Pathogenic (1)		0.000000
324.	c.3476_3477delTT		frameshift	1		Pathogenic (1)	0.000000
325.	c.290C>T	p.A97V	missense	1		VUS favour pathogenic (1)	0.000000
326.	c.2603-2_2603-1delinsGA		essential splice site	1	Pathogenic (1)		0.000000
327.	c.3797G>A	p.C1266Y	missense	1		Likely Pathogenic (1)	0.000000
328.	c.1405C>T	p.Q469X	nonsense	1	Pathogenic (1)		0.000000
329.	c.2040_2041insT	p.Val681CysfsX12	frameshift	1		Pathogenic (1)	0.000000
330.	c.1080G>C	p.K360N	missense	1	VUS (1)		0.000000
331.	c.3580G>A	p.A1194T	missense	1		VUS (1)	0.000008
332.	c.1188G>T	p.W396C	missense	1		VUS (1)	0.000000
333.	c.1756C>G	p.P586A	missense	1	Likely Pathogenic (1)		0.000000
334.	c.3335G>A	p.W1112X	nonsense	1		Pathogenic (1)	0.000000
335.	c.436A>C	p.T146P	missense	1		VUS (1)	0.000000
336.	c.1224-1G>T		essential splice site	1	Pathogenic (1)		0.000000
337.	c.481C>A	p.P161T	missense	1		VUS favour pathogenic (1)	0.000041
338.	c.506-1G>T		essential splice site	1		Pathogenic (1)	0.000000
339.	c.2234A>G	p.D745G	missense	1		VUS (1)	0.000000
340.	c.326C>T	p.A109V	missense	1		VUS (1)	0.000000
341.	c.3019T>C	p.W1007R	missense	1	VUS (1)		0.000000
342.	c.365C>A	p.A122D	missense	1	VUS (1)		0.000000
343.	c.931T>A	p.S311T	missense	1		VUS (1)	0.000000
344.	c.1540A>G	p.I514V	missense	1		VUS (1)	0.000008
345.	c.3572C>T	p.S1191L	missense	1	VUS (1)		0.000016
346.	c.701C>A	p.T234N	missense	1	Likely Pathogenic (1)		0.000000
347.	c.3656T>C	p.L1219P	missense	1	VUS (1)		0.000000
348.	c.1097A>C	p.Q366P	missense	1	VUS (1)		0.000000
349.	c.1624+1G>A		essential splice site	1	Pathogenic (1)		0.000000
350.	c.3049G>A	p.E1017K	missense	1		VUS favour benign (1)	0.000085
351.	c.2909G>A	p.R970Q	missense	1	Likely Pathogenic (1)		0.000032
352.	c.211_212delinsTA	p.Val71*	frameshift	1	Pathogenic (1)		0.000000
353.	c.2938C>T	p.R980C	missense	1		VUS (1)	0.000062
354.	c.2030C>T	p.P677L	missense	1	VUS (1)		0.000000
355.	c.2170C>T	p.R724W	missense	1		VUS (1)	0.000019
356.	c.3257G>A	p.W1086X	nonsense	1	Pathogenic (1)		0.000021
357.	c.1358C>T	p.P453L	missense	1		VUS (1)	0.000008
358.	c.2557G>A	p.G853S	missense	1		VUS (1)	0.000008
359.	c.1291G>A	p.D431N	missense	1	VUS (1)		0.000028
360.	c.631G>A	p.D211N	missense	1	VUS (1)		0.000009
361.	c.1294G>A	p.A432T	missense	1		VUS (1)	0.000037
362.	c.3G>C	p.Met1?	missense	1		Likely Pathogenic (1)	0.000000
363.	c.982delG		frameshift	1	Pathogenic (1)		0.000000
364.	c.3040delC	p.Leu1014TrpfsX6	frameshift	1		Pathogenic (1)	0.000000
365.	c.3334_3351del	p.Trp1112_Glu1117del	inframe	1	Likely Pathogenic (1)		0.000000
366.	c.711C>A	p.Y237X	nonsense	1	Pathogenic (1)		0.000000
367.	c.655-1G>A		essential splice site	1		Pathogenic (1)	0.000000
368.	c.2737+2T>A		essential splice site	1		Pathogenic (1)	0.000000
369.	c.2993A>G	p.Q998R	missense	1		VUS favour pathogenic (1)	0.000000
370.	c.3605G>A	p.C1202Y	missense	1		Likely Pathogenic (1)	0.000000
371.	c.146_148delTCA	p.Ile49del	inframe	1	VUS (1)		0.000039
372.	c.2512dup	p.Glu838Glyfs*46	frameshift	1	Pathogenic (1)		0.000000
373.	c.3332_3335dupAGTG	p.W1112X	nonsense	1		Pathogenic (1)	0.000000
374.	c.3256T>C	p.W1086R	missense	1	VUS (1)		0.000000
375.	c.2708G>A	p.G903D	missense	1	Likely Pathogenic (1)		0.000000
376.	c.2671C>T	p.R891W	missense	1		Likely Pathogenic (1)	0.000031
377.	c.613C>T	p.Q205X	nonsense	1		Pathogenic (1)	0.000000
378.	c.2834G>A	p.R945Q	missense	1	VUS (1)		0.000000
379.	c.3776delA		frameshift	1		Pathogenic (1)	0.000000
380.	c.1266_1267insTGAT	p.Ile423*	frameshift	1	Pathogenic (1)		0.000000
381.	c.3815-1G>A		essential splice site	1		Pathogenic (1)	0.000000
382.	c.1892delT		frameshift	1		Pathogenic (1)	0.000000
383.	c.1457G>A	p.W486X	nonsense	1	Pathogenic (1)		0.000000
384.	c.3753T>G	p.Y1251X	nonsense	1		Pathogenic (1)	0.000000
385.	c.2641G>A	p.V881I	missense	1		VUS (1)	0.000018
386.	c.2939G>A	p.R980H	missense	1		VUS (1)	0.000000
387.	c.1535T>A	p.L512Q	missense	1		VUS favour pathogenic (1)	0.000000
388.	c.1950C>G	p.D650E	missense	1		VUS (1)	0.000000
389.	c.3713T>C	p.L1238P	missense	1	Likely Pathogenic (1)		0.000000
390.	c.1174G>T	p.A392S	missense	1	VUS (1)		0.000000
391.	c.3742G>A	p.G1248R	missense	1		VUS (1)	0.000033
392.	c.518C>A	p.T173N	missense	1		VUS (1)	0.000000
393.	c.1359del	p.Val454Cysfs*12	frameshift	1	Pathogenic (1)		0.000000
394.	c.3605delG		frameshift	1	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.