1 
Table S5: List of gene mutations identified with Sanger sequencing/qPCR in tumor samples 
2 
Case ID 
hmGBC vs
nonhm
tumors 
Site of primary disease 
Gene 
CCDS ID 
mutation
type 
protein 
coding 
function 
exon 
Functional
Domain/Moti
f (HPRD
database) 
COSMIC 
Predicted
functional
implication
(COSMIC) 
3 
CH014 
nonhm 
Extrahepatic 
CTNNB1 
2694.1 
missense 
p.D164E 
c.492C>G 
missense 
3 
ARM 


4 
CH014 
nonhm 
Extrahepatic 
KRAS 
8702.1 
missense 
p.G12A 
c.35G>C 
missense 
1 
RAS 
COSM522 
Pathogenic 
5 
CH040 
nonhm 
Extrahepatic 
PIK3R1 
3993.1 
missense 
p.S429P 
c. 1285T>C 
missense 
9 



6 
CH045 
nonhm 
Extrahepatic 
KRAS 
8702.1 
missense 
p.E63K 
c.187G>A 
missense 
2 
RAS 
COSM27159 
Pathogenic 
7 
CH105 
nonhm 
Extrahepatic 
PTEN 
31238.1 
missense 
p.V365I 
c.1093G>A 
missense 
9 

COSM5056 (rs758542021) 
Pathogenic 
8 
CH112 
nonhm 
Extrahepatic 
CTNNB1 
2694.1 
missense 
p.V167M 
c. 499G>A 
missense 
4 
ARM 


9 
CH112 
nonhm 
Extrahepatic 
PIK3R1 
3993.1 
missense 
p.E485G 
c.1454A>G 
missense 
11 



10 
CH112 
nonhm 
Extrahepatic 
PIK3R1 
3993.1 
missense 
p.L573P 
c. 1718T>C 
missense 
12 

COSM1069619 
Pathogenic 
11 
CH112 
nonhm 
Extrahepatic 
PTEN 
31238.1 
missense 
p.D236N 
c.706G>A 
missense 
7 



12 
CH112 
nonhm 
Extrahepatic 
PTEN 
31238.1 
missense 
p.V351I 
c.1051G>A 
missense 
9 



13 
CH112 
nonhm 
Extrahepatic 
PTEN 
31238.1 
missense 
p.R14T 
c.41G>C 
missense 
1 



14 
CH112 
nonhm 
Extrahepatic 
PTEN 
31238.1 
missense 
p.V365I 
c.1093G>A 
missense 
9 

COSM5056 (rs758542021) 
Pathogenic 
15 
CH147 
nonhm 
Extrahepatic 
CTNNB1 
2694.1 
missense 
p.A117T 
c.349G>A 
missense 
3 



16 
CH159 
nonhm 
Extrahepatic 
CTNNB1 
2694.1 
missense 
p.V122D 
c.365T>A 
missense 
3 



17 
CH159 
nonhm 
Extrahepatic 
PTEN 
31238.1 
nonsense 
p.R233* 
c.697C>T 
nonsense 
7 

COSM5154 
Pathogenic 
18 
CH002 
hmGBC 
Gallbladder 
PTEN 
31238.1 
missenseframeshift 
p.L23fs*1 
c.del68T 
frameshift 
1 



19 
CH018 
hmGBC 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E545K 
c.1633G>A 
missense 
9 
PI3KA 
COSM763 
Pathogenic 
20 
CH120 
hmGBC 
Gallbladder 
PIK3R1 
3993.1 
nonsense 
p.Q415* 
c.1243C>T 
nonsense 
9 

COSM4834480 
Pathogenic 
21 
CH120 
hmGBC 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.S429F 
c.1286C>T 
missense 
9 

COSM5537072 
Pathogenic 
22 
CH120 
hmGBC 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.R577G 
c.1729A>G 
missense 
12 



23 
CH005 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.H259Y 
c.775C>T 
missense 
7 



24 
CH010 
nonhm 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E545K 
c.1633G>A 
missense 
9 
PI3KA 
COSM763 
Pathogenic 
25 
CH010 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.A192T 
c.574G>A 
missense 
6 

COSM1492349 
Pathogenic 
26 
CH010 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.P204L 
c.611C>T 
missense 
6 

COSM1577256 
Pathogenic 
27 
CH010 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.M264I 
c.792G>A 
missense 
7 

COSM5351742 
Pathogenic 
28 
CH026 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.G235E 
c.704G>A 
missense 
4 
ARM 


29 
CH026 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p. E411K 
c.1231G>A 
missense 
9 
SH2 


30 
CH028 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.R274C 
c.820C>T 
missense 
5 
ARM 


31 
CH028 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
nonsense 
p.R544* 
c.1630A>T 
nonsense 
12 
Coiled Coil 
COSM1069604 
Neutral 
32 
CH028 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.S364F 
c.1091C>T 
missense 
9 



33 
CH029 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.S412P 
c. 1234T>C 
missense 
9 
SH2 


34 
CH030 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
nonsense 
p.L581* 
c.1742T>A 
nonsense 
12 



35 
CH032 
nonhm 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E545K 
c.1633G>A 
missense 
9 
PI3KA 
COSM763 
Pathogenic 
36 
CH035 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.H224Y 
c.670C>T 
missense 
4 
ARM 


37 
CH035 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.S229P 
c.685C>T 
missense 
7 



38 
CH035 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.D52N 
c.154G>A 
missense 
2 
DSPC 
COSM5059 
Pathogenic 
39 
CH035 
nonhm 
Gallbladder 
PTEN 
31238.1 
nonsense 
p.E352* 
c.1054G>T 
nonsense 
9 

COSM5297 
Pathogenic 
40 
CH037 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.D299N 
c.895G>A 
missense 
5 
ARM 


41 
CH037 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.N161Y 
c.481A>T 
missense 
3 
ARM 


42 
CH037 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.T201I 
c. 602C>T 
missense 
4 
ARM 


43 
CH037 
nonhm 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E545K 
c.1633G>A 
missense 
9 
PI3KA 
COSM763 
Pathogenic 
44 
CH037 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missenseframeshift 
p.P418fs*5 
c. 1254delC 
frameshift 
9 



45 
CH037 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.G20E 
c.59G>A 
missense 
1 

COSM5094 
Pathogenic 
46 
CH044 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.L229M 
c.685C>A 
missense 
4 
ARM 


47 
CH044 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.M282I 
c. 846G>A 
missense 
5 
ARM 


48 
CH044 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.P154T 
c. 461C>A 
missense 
3 
ARM 


49 
CH044 
nonhm 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E542K 
c.1624G>A 
missense 
9 
PI3KA 
COSM760 
Pathogenic 
50 
CH044 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.D375N 
c.1123G>A 
missense 
9 

COSM5062 
Pathogenic 
51 
CH044 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.S364F 
c.1091C>T 
missense 
9 



52 
CH046 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.K281E 
c.841A>G 
missense 
5 
ARM 


53 
CH047 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.A553T 
c.1657G>A 
missense 
12 
Coiled Coil 


54 
CH055 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.G268R 
c.802G>A 
missense 
5 
ARM 


55 
CH055 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.V283I 
c.847G>A 
missense 
5 
ARM 


56 
CH055 
nonhm 
Gallbladder 
KRAS 
8702.1 
missense 
p.A59T 
c.175G>A 
missense 
2 
RAS 
COSM546 
Pathogenic 
57 
CH055 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.G165R 
c.493G>A 
missense 
6 
DSPC 
COSM5091 
Pathogenic 
58 
CH055 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.S227F 
c.680C>T 
missense 
7 

COSM5095 
Pathogenic 
59 
CH056 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
nonsense 
p.Q309* 
c. 925C>T 
nonsense 
5 
ARM 


60 
CH056 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.M582I 
c.1746G>A 
missense 
13 



61 
CH059 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.V199I 
c.595G>A 
missense 
4 
ARM 
COSM1044591 
Pathogenic 
62 
CH059 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.V283I 
c.847G>A 
missense 
5 
ARM 


63 
CH059 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.R172L 
c.515G>A 
missense 
6 
DSPC 


64 
CH061 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.T120I 
c.359C>T 
missense 
3 



65 
CH062 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.E226K 
c.676G>A 
missense 
4 
ARM 


66 
CH062 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.G216E 
c.647G>A 
missense 
4 
ARM 


67 
CH062 
nonhm 
Gallbladder 
PTEN 
31238.1 
Nonstop extension 
p.*404L (p.*404LIFFYQEG*) 
c.1211G>T 
Nonstop extension 
9 

COSM5333 
Pathogenic 
68 
CH101 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.V175I 
c.523G>A 
missense 
4 
ARM 


69 
CH102 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.H134Y 
c.400C>T 
missense 
3 



70 
CH114 
nonhm 
Gallbladder 
KRAS 
8702.1 
missense 
p.G12D 
c.35G>A 
missense 
1 
RAS 
COSM521 
Pathogenic 
71 
CH114 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.R41G 
c.121A>G 
missense 
2 
DSPC 


72 
CH130 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missenseframeshift 
p.A295fs*10 
c.883delG 
frameshift 
5 
ARM 


73 
CH130 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.L244F 
c.730C>T 
missense 
4 
ARM 


74 
CH130 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.R577K 
c.1730G>A 
missense 
12 

COSM1069630 
Pathogenic 
75 
CH132 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.P100L 
c.299C>T 
missense 
3 



76 
CH132 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.S412F 
c. 1235C>T 
missense 
9 
SH2 


77 
CH132 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.V222M 
c.664G>A 
missense 
7 



78 
CH132 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.P244S 
c.730C>T 
missense 
7 

COSM5119 
Pathogenic 
79 
CH133 
nonhm 
Gallbladder 
KRAS 
8702.1 
missense 
p.G13D 
c.38G>A 
missense 
1 
RAS 
COSM532 
Pathogenic 
80 
CH136 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.A116V 
c.347C>T 
missense 
3 



81 
CH136 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.A284T 
c.850G>A 
missense 
5 
ARM 


82 
CH136 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.A2T 
c.4G>A 
missense 
1 



83 
CH136 
nonhm 
Gallbladder 
PIK3CA 
43171.1 
missense 
p.E542K 
c.1624G>A 
missense 
9 
PI3KA 
COSM760 
Pathogenic 
84 
CH136 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.A192V 
c.575C>T 
missense 
6 



85 
CH142 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.P190L 
c.569C>T 
missense 
6 

COSM249903 
none 
86 
CH155 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.M88I 
c.264G>A 
missense 
3 



87 
CH155 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.M582I 
c.1746G>A 
missense 
13 



88 
CH155 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.D381N 
c.1141G>A 
missense 
9 



89 
CH156 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.M131T 
c.392C>T 
missense 
3 



90 
CH156 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.C105Y 
c.314G>A 
missense 
5 
DSPC 
COSM5113 
Pathogenic 
91 
CH158 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.D569N 
c.1705A>G 
missense 
12 



92 
CH158 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.V175E 
c.524T>A 
missense 
6 
DSPC 


93 
CH177 
nonhm 
Gallbladder 
KRAS 
8702.1 
missense 
p.G12A 
c.35G>C 
missense 
1 
RAS 
COSM522 
Pathogenic 
94 
CH177 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
nonsense 
p. W597* 
c. 1791G>A 
nonsense 
13 



95 
CH184 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.M582V 
c.1744A>G 
missense 
12 



96 
CH184 
nonhm 
Gallbladder 
PIK3R1 
3993.1 
missense 
p.R577S 
c.1731A>G 
missense 
12 



97 
CH185 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.M107I 
c.321G>A 
missense 
3 



98 
CH185 
nonhm 
Gallbladder 
CTNNB1 
2694.1 
missense 
p.V166M 
c. 496G>A 
missense 
4 
ARM 


99 
CH185 
nonhm 
Gallbladder 
PTEN 
31238.1 
missense 
p.H185Y 
c.553C>T 
missense 
6 



100 
CH008 
nonhm 
Intrahepatic 
CTNNB1 
2694.1 
missense 
p.A269V 
c.806C>T 
missense 
5 
ARM 


101 
CH008 
nonhm 
Intrahepatic 
KRAS 
8702.1 
missense 
p.G12V 
c.35G>T 
missense 
1 
RAS 
COSM520 
Pathogenic 
102 
CH008 
nonhm 
Intrahepatic 
PTEN 
31238.1 
nonsense 
p.Q214* 
c.640C>T 
nonsense 
7 

COSM5150 (rs121909227) 
Pathogenic 
103 
CH008 
nonhm 
Intrahepatic 
PTEN 
31238.1 
missense 
p.P367L 
c.1100C>T 
missense 
9 



104 
CH163 
nonhm 
Intrahepatic 
CTNNB1 
2694.1 
missense 
p.V122I 
c.364G>A 
missense 
4 



105 
CH163 
nonhm 
Intrahepatic 
KRAS 
8702.1 
missense 
p.G12A 
c.35G>C 
missense 
1 
RAS 
COSM522 
Pathogenic 
106 
CH166 
nonhm 
Intrahepatic 
CTNNB1 
2694.1 
missense 
p.K288R 
c.863A>G 
missense 
5 
ARM 


107 
CH166 
nonhm 
Intrahepatic 
PTEN 
31238.1 
missense 
p.P204L 
c.611C>T 
missense 
6 

COSM1577256 
Pathogenic 
108 
CH168 
nonhm 
Intrahepatic 
PIK3R1 
3993.1 
missense 
p.A360T 
c.1078G>A 
missense 
8 
SH2 


109 
CH168 
nonhm 
Intrahepatic 
PIK3R1 
3993.1 
missense 
p.M582I 
c.1746G>A 
missense 
13 



110 
CH176 
nonhm 
Intrahepatic 
CTNNB1 
2694.1 
missense 
p.G277D 
c.830G>A 
missense 
5 
ARM 
COSM1044594 
Pathogenic 
111 
CH176 
nonhm 
Intrahepatic 
PIK3CA 
43171.1 
missense 
p.A1046T 
c.3136G>A 
missense 
20 
PI3KC 
COSM27273 
Pathogenic 
112 
CH176 
nonhm 
Intrahepatic 
PIK3CA 
43171.1 
missense 
p.S1003P 
c.3007T>C 
missense 
20 
PI3KC 
COSM328020 
Pathogenic 
113 
CH176 
nonhm 
Intrahepatic 
PIK3R1 
3993.1 
nonsense 
p.L424* 
c.1271T>A 
nonsense 
9 



114 
CH176 
nonhm 
Intrahepatic 
PIK3R1 
3993.1 
missense 
p.R503Q 
c.1508G>A 
missense 
11 


Pathogenic 
115 
CH176 
nonhm 
Intrahepatic 
PTEN 
31238.1 
missense 
p.R41G 
c.121A>G 
missense 
2 
DSPC 


116 
CH180 
nonhm 
Intrahepatic 
PIK3R1 
3993.1 
missense 
p. K382E 
c.1144A>G 
missense 
9 
SH2 

