Details Of Published TSH Receptor Mutation

Leu 629 Phe

c.1887G>T

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default 
Clinical Features:
based on 19 hot nodules investigated by Tonacchera et al. 1998,1999 and 2000, Stephenson et al. 2020, Gozu et al. 2005 and 2006, Sancak et al. 2011, Parma et al. 1997, Georgopoulos et al. 2003, Palos-Paz et al. 2008
and on 1 activating familial germline mutation investigated by Fuhrer et al. 1997


cDNA exchange: TTG>TTC/TTT 
Treatment:
default
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(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
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:
Parma et al.
J. Clin. Endocrinol. Metab. 82: 2695-2701
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas
1997
Reference 2:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 83: 492-498
Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma
1998
Reference 3:
Tonacchera et al.
J. Clin. Endocrinol. Metab. 84: 4155-4158
Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms
1999
Reference 4:
Wonerow et al.
Clin. Endocrinol. 53: 461-468
Functional characterization of five constitutively activating thyrotrophin receptor mutations
2000
Reference 5:
Wonerow et al.
J. Biol. Chem. 273: 7900-7905
Deletions in the third intracellular loop of the thyrotropin receptor. A new mechanism for constitutive activation.
1998
Reference 6:
Tonacchera et al.
J Clin Endocrinol Metab. 85: 2270-4
Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.
2000
Reference 7:
Gozu et al.
Eur J Endocrinol. 155: 535-45
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
2006
Reference 8:
Gozu et al.
Endocr J. 52: 577-85
Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population.
2005
Reference 9:
Sancak et al.
Horm Metab Res. 43:562-8
High Prevalence of TSHR/Gsalpha Mutation-negative Clonal Hot Thyroid Nodules (HNs) in a Turkish Cohort
2011
Reference 10:
Mueller et al.
Thyroid. 19(7):765-73
Cases of borderline in vitro constitutive thyrotropin receptor activity: how to decide whether a thyrotropin receptor mutation is constitutively active or not?
2009
Reference 11:
Stephenson et al.
Thyroid
Sensitive Sequencing Analysis Suggests Thyrotropin Receptor and Guanine Nucleotide-Binding Protein G Subunit Alpha as Sole Driver Mutations in Hot Thyroid Nodules
2020