Details Of Published TSH Receptor Mutation
Phe 631 Ile
c.1891T>AConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
based on 4 hot nodules investigated by Sancak et al. 2011 and Stephenson et al. 2020
Clinical Features:
default
Treatment:
default
Functional Characteristics:
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
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:
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 2:
Nishihara et al.
Endocr J. 56:791-8
Prevalence of TSH receptor and Gsalpha mutations in 45 autonomously functioning thyroid nodules in Japan.
2009
Reference 3:
Jäschke et al.
Clin Endocrinol (Oxf) 73:815-20
Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas
2010
Reference 4:
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