Details Of Published TSH Receptor Mutation

Ala 593 Asn

c.1778C>A; c.1777G>A

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default 
Clinical Features:
based on 1 hot nodule investigated by Georgopoulos et al. 2003 
Treatment:
default
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.4
1.3
n.d.
n.d.
0.4
1
2
Legend:
cAMP (basal): basal in vitro cAMP production of mutant over wild-type TSHR
cAMP (TSH): maximal in vitro cAMP production of mutant over wild-type TSHR
IP (basal): basal in vitro IP production of mutant over wild-type TSHR
IP (TSH): maximal in vitro IP production of mutant over wild-type TSHR
TSH-binding: maximal TSH-binding compared to the wild-type TSHR
Cell surface expression: cell surface expression of mutant compared to WT-TSHR
LRA: linear regression analysis (LRA) of constitutive activity as a function of TSHR expression determined by 125I-bTSH binding or FACS analysis compared to the wild-type TSHR
Prevalence: Prevalence of (somatic and germline) activating mutations*
Ref: Reference for functional characterization
Child: Found in children.
Reference 1:
Georgopoulos et al.
Eur J Endocrinol. 149: 287-92
Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway.
2003
Reference 2:
Sykiotis et al.
Biochem Biophys Res Commun 301:1051-1056
Functional significance of the thyrotropin receptor germline polymorphism D727E.
2003