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NM_000369.5(TSHR):c.928C>T (p.Arg310Cys) AND Hypothyroidism due to TSH receptor mutations

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 1, 2000
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000006827.4

Allele description [Variation Report for NM_000369.5(TSHR):c.928C>T (p.Arg310Cys)]

NM_000369.5(TSHR):c.928C>T (p.Arg310Cys)

Gene:
TSHR:thyroid stimulating hormone receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q31.1
Genomic location:
Preferred name:
NM_000369.5(TSHR):c.928C>T (p.Arg310Cys)
HGVS:
  • NC_000014.9:g.81142986C>T
  • NG_009206.1:g.192462C>T
  • NM_000369.2:c.928C>T
  • NM_000369.5:c.928C>TMANE SELECT
  • NP_000360.2:p.Arg310Cys
  • LRG_523t1:c.928C>T
  • LRG_523:g.192462C>T
  • NC_000014.8:g.81609330C>T
Protein change:
R310C; ARG310CYS
Links:
OMIM: 603372.0027; dbSNP: rs121908882
NCBI 1000 Genomes Browser:
rs121908882
Molecular consequence:
  • NM_000369.5:c.928C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypothyroidism due to TSH receptor mutations
Synonyms:
HYPOTHYROIDISM DUE TO UNRESPONSIVENESS TO THYROTROPIN; HYPOTHYROIDISM, CONGENITAL, DUE TO TSH RESISTANCE; HYPOTHYROIDISM, NONAUTOIMMUNE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010142; MedGen: C3493776; Orphanet: 90673; OMIM: 275200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000027023OMIM
no assertion criteria provided
Pathogenic
(Nov 1, 2000) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH.

Russo D, Betterle C, Arturi F, Chiefari E, Girelli ME, Filetti S.

J Clin Endocrinol Metab. 2000 Nov;85(11):4238-42.

PubMed [citation]
PMID:
11095460

Details of each submission

From OMIM, SCV000027023.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

Russo et al. (2000) reported 2 sibs, born of consanguineous parents, who had resistance to TSH and euthyroid hyperthyrotropinemia ('compensated hypothyroidism') (CHNG1; 275200). By direct sequencing of the TSHR gene, they identified a novel mutation in the TSHR gene, resulting in an arg310-to-cys (R310C) substitution in the extracellular domain of the protein. The mutation was homozygous in the 2 affected brothers; heterozygous in both parents, an uncle, and an unaffected brother; and absent in the other unaffected brother. When stably transfected in Chinese hamster ovary cells, the mutant allele showed loss of response to TSH in terms of cAMP stimulation. However, a constitutive activity in terms of basal cAMP production was detected in the mutant, compared with wildtype, TSHR. The authors concluded that the R310C TSHR mutant may determine both the TSH resistance and the clinical euthyroidism detected in this family.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 18, 2023