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Gln 8 His
c. 24C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 27 Thr
c.79C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Cys 31 Stop
c.91C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Glu 34 Lys
c.100G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Cys 41 Ser
c.122G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
0
nd
nd
0
0
6
Cys 41
-> 4bp dup
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 46 Pro
c.137G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 51 Gln
c.152C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 68 Ser
c.202C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
Pro 68 Ser
c.202C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5
Val 87 Leu
c.259G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gln 90 Pro
c.269A>C; c.270G>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 109 Gln
c.326G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
~
+
nd
nd
+
nd
3
Arg 109 Gln
c.326G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5
Gly 132 Arg
c.394G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Gly 132 Arg
c.394G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Thr 145 Ile
c.434C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 162 Ala
c.484C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
nd
nd
+
-
13
Pro 162 Ala
c.484C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8
Pro 162 Leu
c.485C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ile 167 Asn
c.500T>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
nd
0
0
1
Ile 167 Met
c.501C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Lys 183 Arg
c.548A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
~
~
nd
nd
~
~
1
Lys 183 Asn
c.549G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
Ala 204 Val
c.611C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ser 234 Pro
c.700C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gly 245 Ser
c.733G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gly 245 Ser
c.733G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Leu 252 Pro
c.755T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Pro 264 Ser
c.790C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
Leu 267 Phe
c.808C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
His 271 Asn
c.811C>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
170
94
106
76
83
1
2.7+/-0.4
1
Ala 275 Thr
c.823G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ser 281 Asn
c.842G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-5.3
0.7-1.2
0.6-1.3
0.5-1.3
nd
0.2-0.6
12
7.9+/-0.1;15.1+/-2.9
3,5,10,11,12
Ser 281 Asn
c.842G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-5.3
0.7-1.2
0.6-1.3
0.5-1.3
~
-
1
7.9+/-0.1;15.1+/-2.9
Ser 281 Asn
c.842G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-5.3
0.7-1.2
0.6-1.3
0.5-1.3
ND
ND
2
7.9+/-0.1;15.1+/-2.9
Ser 281 Ile
c.842G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7-8
0.61
1-3.7
0.6-0.9
0,23
6
25.1+/-7.9
1-3
Ser 281 Thr
c.842G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-4.4
0.9-1.0
0.7-1.0
0.7-1.0
nd
0.76
6
7.0+/-1.3
3,8,9
Ser 305 Arg
c.915T>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Arg 310 Cys
c.928C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
+
0
nd
nd
(0)
nd
2
317
c.317+1G->A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gln 324 Stop
c.970C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
nd
nd
nd
nd
nd
nd
1
Cys 390 Phe
c.1169G>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Cys 390 Trp
c.1170T>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
~
+
nd
nd
+
-
3
Asp 403 Asn
c.1207G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
Asn 406 Ser
c.1217A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
224, 225
Cys 408 Arg
c.1222T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Asp 410 Asn
c.1228G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
nd
nd
-
-
3
Val 424 Ile
c.1270G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Val 424 Phe
c.1270G>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ser 425 Ile
c.1274G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8.3
0.8
nd
nd
nd
0.76
7
n.d.
1
Ala 428 Ile
c.1283C>T; c.1282G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.3
0.9
1.35
0.7
0.45
1
6.4+/-0.5
1
Ala 428 Val
c.1283C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.4
0.9
n.d.
n.d.
0.25
2
88.2+/-2.1
Ala 428 Val
c.1283C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.4
0.9
1.35
0.71
0.25
2
88.2+/-2.1
1
Gly 431 Ser
c.1292G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.5-6.3
0.6-1.3
0.7-1.4
0.8-1.1
~
0.9
4
4.9+/-0.5;5.8+/-0.6
1,3,4
Gly 431 Ser
c.1292G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.5-6.3
0.6-1.3
0.7-1.4
0.8-1.1
0.9
2
4.9+/-0.5;5.8+/-0.6
1,3,4
Asn 432 Asp
c.1294A>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
0
nd
0
1
nd
Tyr 444 Stop
c.1332C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 449 Leu
c.1346C>U
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.805 +/-0
0.611 +/-0
nd
0.169 +/-0
nd
1.191
1
nd
Arg 450 His
c.1349G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
nd
nd
+
-
16
Arg 450 His
c.1349G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
9
Met 453 Arg
c.1358T>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8.53 +/- 1
0.479+/-0.
1
0
nd
0.806+/-0.
1
Met 453 Arg
c.1358T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8.53 +/- 1
0.479+/-0.
1
0
nd
0.806+/-0.
1
Met 453 Thr
c.1358T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.7-7.0
0.8
1.0
0.8-1.0
nd
0.66
49
5.2+/-0.8
1,10,11
Met 453 Thr
c.1358T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.7-7.0
0.8
1.0
0.8-1.0
nd
0.66
3
5.2+/-0.8
Met 453 Thr
c.1358T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.7-7.0
0.8
1.0
0.8-1.0
nd
0.66
3
5.2+/-0.8
1,3,4
Met 453 Thr
c.1358T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.7-7.0
0.8
1.0
0.8-1.0
0.66
1
5.2+/-0.8
1,3,4
Cys 462 Arg
c.1384T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Met 463 Val
c.1387A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.0-3.3
1.8
1.0
n.d.
-
0.6
4
13.5+/-0.7
1,5
Met 463 Val
c.1387A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.0-3.3
1.8
1.0
n.d.
n.d.
0.6
2
13.5+/-0.7
1,3
Tyr 466 Cys
c.1397A>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Leu 467 Pro
c.1400T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
0
nd
nd
nd
-
1
Val 473 Ile
c.1418G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Thr 477 Ile
c.1431C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
nd
-
(0)
1
Ala 485 Val
c.1454T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.7
n.d.
1.0
0.05
0.03
1
1,2
Ile 486 Asn
c.1457T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7.1
0.8
n.d.
n.d.
0.6
1
6.7+/-1.4
1
Ile 486 Asn
c.1457T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7.1
0.8
n.d.
n.d.
0.6
1
6.7+/-1.4
1
Ile 486 Met
c.1458C>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.3
1.1
1.2-1.7
1.8
-
0.5-0.8
13
5.1 +/- 0.6
1,11
Ile 486 Phe
c.1456A>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.0-8.2
0.8
1.0-3.3
0.4
0.2-0.4
14
57.8+/-6.9
1,5,6,11
Ile 486 Phe
c.1457T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.0-8.2
0.8
1.0-3.3
0.4
-
0.2-0.4
2
57.8+/-6.9
1,2,5,6
Trp 488 Arg
c.1462T>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gln 489 His
c.1467G>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gly 498 Ser
c.1492G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
nd
(0)
0
1
Ser 505 Arg
c.1513G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-2.9
0.7-1.0
1.0
0.5
-
0.6-0.8
2
6.1+/-0.9
2,3,5,7
Ser 505 Asn
c.1513G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5-6.5
1.1
0.8-0.9
1-1.2
-
0.8
3
4.5+/-0.3
1,3,4,5
Ser 505 Asn
c.1513G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5-6.5
1.1
0.8-0.9
1-1.2
0.8
1
4.5+/-0.3
1,2,4,5
Ser 505 Asn
c.1513G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5-6.5
1.1
0.8-0.9
1-1.2
0.8
4
4.5+/-0.3
1,2,5,7
Val 509 Ala
c.1526T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.0
n.d.
n.d.
n.d.
-
n.d.
2
2,3
Leu 512 Arg
c.1535T>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3
0.5
1.0
0.1
-
0.6
7
1
Leu 512 Arg
c.1535T>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3
0.5
1.0
0.1
0.6
1
1
Leu 512 Gln
c.1535T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-4.6
0.7-0.9
0.9
0.5
0.9-1.0
8
4.5+/-0.7
1,6,7
Leu 512 Gln
c.1535T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-4.6
0.7-0.9
0.9
0.5
ND
0.9-1.0
1
4.5+/-0.7
Leu 512 Met
c.1534C>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
Arg 519 Cys
c.1555C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Arg 519 Gly
c.1555C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Phe 525 Leu
c.1575C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
nd
nd
~
-
1
Phe 525 Ser
c.1574T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Phe 525 Ser
c.1574T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ala 526 Thr
c.1576G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Met 527 Thr
c.1580C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Arg 528 Cys
c.1582C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 531 Trp
c.1591C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 531 Trp
c.1591C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Gly 544 Glu
c.1631G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Trp 546 Stop
c.1637G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0
0
nd
nd
(0)
nd
4
Ala 553 Thr
c.1657G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
+
~
0
-
-
4
Leu 555 Stop
Del555-561
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Pro 556 Arg
c.1667C>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ile 568 Phe
c.1702A>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.4
1.1
nd
nd
1
nd
3
nd
Ile 568 Phe
c.1702A>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ile 568 Thr
c.1703T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.2
0.9
0.8-2.2
0.8
-
0.4-0.7
17
25.6+/-6.3
1,10,11
Ile 568 Thr
c.1703T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.2
0.9
0.8-2.2
0.8
-
0.4-0.7
2
1,5,6
Ile 568 Thr
c.1703T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.2
0.9
0.8-2.2
0.8
-
0.4-0.7
1
Ile 568 Val
c.1702A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-2.9
0.8
0.9-1.0
1.1
0.8-1.0
1
1.9+/-0.8;4.4+/-0.1
1-4
Glu 575 Lys
c.1723G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.0
2.42?±?0.4
1
1
Ile 583 Thr
c.1748T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ala 593 Asn
c.1778C>A; c.1777G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.4
1.3
n.d.
n.d.
0.4
1
2
Ala 593 Val
c.1778C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Val 597 Leu
c.1789G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-6.8
0.5
n.d.
n.d.
-
0.1-0.2
1
125.2±10.5
1-3
Val 597 Leu
c.1789G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-6.8
0.5
n.d.
n.d.
0.1-0.2
1
125.2±10.5
1,2,4
Val 597 Phe
c.1789G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.0-4.5
0.7-1.0
n.d.
n.d.
nd
0.3-0.4
2
24.3+/-4.3
1,2
Val 597 Phe
c.1789G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.0-4.5
0.7-1.0
n.d.
n.d.
0.3-0.4
1
24.3+/-4.3
1,3
Cys 600 Arg
c.1798T>C
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
-
0
nd
nd
nd
-
1
Tyr 601 Asn
c.1801T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.2-4.8
0.5-1.2
0.9-1.1
0.2-0.5
nd
0.3-0.6
3
5.9±0.1
1,2,4
Thr 607 Ile
c.1820C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 609 Gln
c.1826G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Arg 609 Stop
c.1825C>T
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
nd
nd
nd
nd
nd
nd
3
Tyr 613 Cys
c.1838A>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Tyr 613 Cys
c.1838A>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
613
del3ICL
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
8
0.5
2
0.4
nd
1
1
Asp 617 Tyr
c.1849G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4
0.9
0.9
0.8
0.6
1
1
Asp 619 Gly
c.1856A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-1.8
0.9-1.0
0.9
0.8-0.9
-
0.6
19
1,11,12
Asp 619 Gly
c.1856A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.4-1.8
0.9-1.0
0.9
0.8-0.9
-
0.6
1
-
226
Thr 620 Ile
c.1859C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.7
1.1
1.1
0.6
1.0
1
0.4±0.1
1
Ala 623 Cys
c.1867G>T; c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
nd
nd
nd
nd
nd
nd
1
4.6±0.4
1
Ala 623 Gly
c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
Ala 623 Ile
c.1867G>A; c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.8
n.d.
1.0
n.d.
-
n.d.
2
1
Ala 623 Phe
c.1867G>T; c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.3-0.4
1.0
n.d.
n.d.
0.5
1
1,2
Ala 623 Ser
c.1867G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.5
n.d.
n.d.
n.d.
nd
n.d.
7
1
Ala 623 Ser
c.1867G>T; c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.5
n.d.
n.d.
n.d.
nd
n.d.
3
1
Ala 623 Val
c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.5-5.0
0.8-1.2
0.9-1.0
1.0
-
1.0
21
5.0±0.7
1,13
Ala 623 Val
c.1868C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.5-5.0
0.8-1.2
0.9-1.0
1.0
-
1.0
1
2,3
Met 626 Ile
c.1877G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.5-4.9
1.0
1.0
1.3
0.3-0.7
2
6.8±0.4
1,2
Ala 627 Val
c.1880C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.2
0.5
n.d.
n.d.
0.5
1
4.2±1.0
1
Leu 629 Phe
c.1887G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.1-6.5
0.8-0.9
1.0-1.1
0.2
~
0.7
19
6.9±0.6
2,3,4,5
Leu 629 Phe
c.1887G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.1-6.5
0.8-0.9
1.0-1.1
0.2
~
0.7
1
6.9±0.6
2,3,4,5
Ile 630 Leu
c.1888A>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.5-6.4
0.8-1.1
0.9
0.3
~
0.4
12
2,3,4
Ile 630 Leu
c.1888A>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.5-6.4
0.8-1.1
0.9
0.3
ND
0.4
1
ND
Ile 630 Leu
c.1888A>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Phe 631 Cys
c.1892T>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.0
1.0
1.0
0.9
-
n.d.
1
2
Phe 631 Ile
c.1891T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7
0.8
1.1
0.2
0.4
1
8.6 ± 0.7
1
Phe 631 Ile
c.1891T>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7
0.8
1.1
0.2
0.4
4
8.6 ± 0.7
3
Phe 631 Leu
c.1893C>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.0
1.0
n.d.
1.0
-
n.d.
20
45.9±9.4
1,11
Phe 631 Leu
c.1891T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.0
1.0
n.d.
1.0
-
n.d.
1
45.9±9.4
1,3
Phe 631 Leu
->
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Phe 631 Ser
c.1892T>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
7.0
1.0
1.0
0.4
0.4
1
1
Thr 632 Ala
c.1894A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.2
1.5
n.d.
n.d.
nd
0.4-0.5
1
1,3
Thr 632 Ala
c.1894A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.2
1.5
n.d.
n.d.
0.4-0.5
7
2,7
Thr 632 Ile
c.1895C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-5.0
0.8-1.0
1.0-1.3
0.7-1.0
-
n.d.
3
14.5±2.7
2,4,5
Thr 632 Ile
c.1895C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-5.0
0.8-1.0
1.0-1.3
0.7-1.0
-
n.d.
2
1,3,4
Thr 632 Ile
c.1895C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7-5.0
0.8-1.0
1.0-1.3
0.7-1.0
n.d.
58
1,3,5
Asp 633 Ala
c1898A>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.4
1.3
n.d.
n.d.
nd
0.2-0.3
1
2,3
Asn 633 Glu
c1899C>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.9
1
0.9-1.3
0.6
-
0.7
2
Asp 633 Glu
c1899C>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-3.9
1.0
0.9-1.3
0.6
-
0.7
14
5,7
Asp 633 His
c1897G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.2
0.7
2.2
1.0
nd
0.8
13
Asp 633 His
c1897G>C
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
6.2
0.7
2.2
1.0
nd
0.8
1
2
Asp 633 Tyr
c1897G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
-
n.d.
18
16.4±6.4
6,10
Asp 633 Tyr
c1897G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
-
n.d.
1
16.4±6.4
1,3
Asp 633 Tyr
c1897G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
ND
ND
1
16.4±6.4
Ile 635 Val
c.1903A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.7
n.d.
n.d.
n.d.
n.d.
1
1
Cys 636 Trp
c.1908C>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.9
0.9
0.2
1.0
0.2
1
1
Pro 639 Ala
c.1915C>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
n.d.
n.d.
n.d.
n.d.
n.d.
1
1
Pro 639 Ser
c.1915C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.8-5.0
1.1
2.4
0.2
0.7
2
1,3
Pro 639 Ser
c.1915C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.8-5.0
1.1
2.4
0.2
-
0.7
1
2,3
Pro 639 Ser
c.1915C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.8-5.0
1.1
2.4
0.2
-
0.7
1
Ile 640 Lys
c.1919T>A; c.1920C>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
5.9
0.5
n.d.
n.d.
0.4
1
14.6±2.2
1
Ala 644 Asp
c.1931C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Ala 647 Val
c.1940C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
ND
1
Asn 650 Tyr
c.1948A>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.6
1.0
1.0
n.d.
~
n.d.
1
1
Leu 653 Val
c.1957C>g
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2
Val 656 Phe
c.1966G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1-7.1
0.8-1.1
0.9
0.5-1.0
-
0.8-1.0
4
4.1 ± 0.9
1,2,6,5
Val 656 Phe
c.1966G>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1-7.1
0.8-1.1
0.9
0.5-1.0
-
0.9-1.0
1
4.1 ± 0.9
Ile 661 Stop
->
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Leu 665 Phe
CTC -> TTC
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
1.2
1
1.1
nd
1.02
1
2.3
Phe 666 Leu
c.1996C>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.6
0.9
0.8
0.2
nd
1.0
1
0.8 ± 0.1
2
Asn 670 Ser
c.2009A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.7-2.4
0.6
n.d.
n.d.
-
1.0
1
0.5±0.1;2.5
2
Asn 670 Ser
c.2009A>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.7-2.4
0.6
n.d.
n.d.
n.d.
1
1
0.5±0.1;2.5
Cys 672 Thr
c.2015G>A
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
2.2-3.3
0.5-0.7
n.d.
n.d.
-
0.4
1
4.2±0.5
1-3
Cys 672 Trp
c.2016T>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
ND
ND
ND
ND
ND
ND
1
Leu 677 Val
c.2029C>G
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1.0-3.4
0.7
1.0
0.2
nd
0.6
1
1.4±0.6
2
Ala 684 Asp
c.2051C>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Val 689 Gly
c.2066T>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3
Ile 691 Phe
c.2071A>T
Constitutively Activating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
0.8
0.7
1.1
0.9
0.9
1
0.7±0.1
2
Phe 696 Cys
c.2087T>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Lys 700 Glu
c.2098A>G
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Glu 758 Lys
c.2272G>A
Inactivating TSH Receptor Mutation
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
1
Q
8
P
27
X
31
E
34
C
41
C
41
R
46
P
51
P
68
P
68
V
87
Q
90
R
109
R
109
G
132
G
132
T
145
P
162
P
162
P
162
I
167
I
167
K
183
K
183
A
204
S
234
G
245
G
245
L
252
P
264
L
267
H
271
A
275
S
281
S
281
S
281
S
281
S
281
S
305
R
310
X
317
X
324
C
390
C
390
D
403
N
406
C
408
D
410
V
424
V
424
S
425
A
428
A
428
A
428
G
431
G
431
N
432
X
444
P
449
R
450
R
450
M
453
M
453
M
453
M
453
M
453
M
453
C
462
M
463
M
463
Y
466
L
467
V
473
T
477
A
485
I
486
I
486
I
486
I
486
I
486
W
488
Q
489
G
498
S
505
S
505
S
505
S
505
V
509
L
512
L
512
L
512
L
512
L
512
R
519
R
519
F
525
F
525
F
525
A
526
M
527
R
528
R
531
R
531
G
544
X
546
A
553
X
555
P
556
I
568
I
568
I
568
I
568
I
568
I
568
E
575
I
583
A
593
A
593
V
597
V
597
V
597
V
597
C
600
Y
601
T
607
R
609
X
609
Y
613
Y
613
X
613
D
617
D
619
D
619
T
620
A
623
A
623
A
623
A
623
A
623
A
623
A
623
A
623
M
626
A
627
L
629
L
629
I
630
I
630
I
630
F
631
F
631
F
631
F
631
F
631
F
631
F
631
T
632
T
632
T
632
T
632
T
632
D
633
N
633
D
633
D
633
D
633
D
633
D
633
D
633
I
635
C
636
P
639
P
639
P
639
P
639
I
640
A
644
A
647
N
650
L
653
V
656
V
656
X
661
L
665
F
666
N
670
N
670
C
672
C
672
L
677
A
684
V
689
I
691
F
696
K
700
E
758