NM_001354712.2(THRB):c.959G>A (p.Arg320His) AND Thyroid hormone resistance, generalized, autosomal dominant

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 12, 2012
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:: RCV000013380.18

Allele description [Variation Report for NM_001354712.2(THRB):c.959G>A (p.Arg320His)]

NM_001354712.2(THRB):c.959G>A (p.Arg320His)

Gene:

THRB:thyroid hormone receptor beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.2

Genomic location:

Preferred name:

NM_001354712.2(THRB):c.959G>A (p.Arg320His)

HGVS:

NC_000003.12:g.24127684C>T
NG_009159.1:g.372139G>A
NM_000461.5:c.959G>A
NM_001128176.3:c.959G>A
NM_001128177.2:c.959G>A
NM_001252634.2:c.959G>A
NM_001354708.2:c.959G>A
NM_001354709.2:c.959G>A
NM_001354710.2:c.959G>A
NM_001354711.2:c.959G>A
NM_001354712.2:c.959G>AMANE SELECT
NM_001354713.2:c.959G>A
NM_001354714.2:c.866G>A
NM_001354715.2:c.866G>A
NP_000452.2:p.Arg320His
NP_001121648.1:p.Arg320His
NP_001121649.1:p.Arg320His
NP_001239563.1:p.Arg320His
NP_001341637.1:p.Arg320His
NP_001341638.1:p.Arg320His
NP_001341639.1:p.Arg320His
NP_001341640.1:p.Arg320His
NP_001341641.1:p.Arg320His
NP_001341642.1:p.Arg320His
NP_001341643.1:p.Arg289His
NP_001341644.1:p.Arg289His
NC_000003.11:g.24169175C>T
NM_000461.4:c.959G>A
NM_001252634.1:c.959G>A
P10828:p.Arg320His

Protein change:

R289H; ARG320HIS

Links:

UniProtKB: P10828#VAR_004637; OMIM: 190160.0015; dbSNP: rs121918693

NCBI 1000 Genomes Browser:

rs121918693

Molecular consequence:

NM_000461.5:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128176.3:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128177.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001252634.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354708.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354709.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354710.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354711.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354712.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354713.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354714.2:c.866G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354715.2:c.866G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Thyroid hormone resistance, generalized, autosomal dominant (GRTHD)
Synonyms:: HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES
Identifiers:: MONDO: MONDO:0008569; MedGen: C2937288; OMIM: 188570

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033627	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 1993)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 1314846, 8514853
SCV000692418	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	no assertion criteria provided	Pathogenic (Oct 12, 2012)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033627

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 1993)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000692418

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

no assertion criteria provided

Pathogenic
(Oct 12, 2012)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid hormone receptor in a kindred with generalized resistance to thyroid hormones results in a receptor with significant 3,5,3'-triiodothyronine binding activity.

Cugini CD Jr, Leidy JW Jr, Chertow BS, Bérard J, Bradley WE, Menke JB, Hao EH, Usala SJ.

J Clin Endocrinol Metab. 1992 May;74(5):1164-70.

PubMed [citation]

PMID:: 1314846

Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families.

Weiss RE, Weinberg M, Refetoff S.

J Clin Invest. 1993 Jun;91(6):2408-15.

PubMed [citation]

PMID:: 8514853
PMCID:: PMC443299

Details of each submission

From OMIM, SCV000033627.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Cugini et al. (1992) described autosomal dominant generalized thyroid hormone resistance (GRTHD; 188570) due to a guanine-to-adenine transition at nucleotide 1244, resulting in a change of arginine-315 to histidine (ARG315HIS). Affected members of this kindred appeared to have a relatively mild degree of resistance, with mean total thyroxine of only 192 +/- 24 nmol/L and inappropriately normal TSH levels. The oldest affected member studied was 62. The mutation was located further upstream than most previously described mutations; only ala312 to thr was further upstream.

Weiss et al. (1993) found this mutation (designated arg320 to his in the new nomenclature) in 2 separate families with GRTHD. The distinctness of the mutant allele in the 2 families was supported by the fact that each was associated with a different CA repeat polymorphism. The change was a G-to-A transition at nucleotide 1244 in exon 9.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000692418.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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