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

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.