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NM_001354712.2(THRB):c.1373T>C (p.Val458Ala) AND not provided

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Sep 18, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000986043.3

Allele description [Variation Report for NM_001354712.2(THRB):c.1373T>C (p.Val458Ala)]

NM_001354712.2(THRB):c.1373T>C (p.Val458Ala)

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.1373T>C (p.Val458Ala)
HGVS:
  • NC_000003.12:g.24122897A>G
  • NG_009159.1:g.376926T>C
  • NM_000461.5:c.1373T>C
  • NM_001128176.3:c.1373T>C
  • NM_001128177.2:c.1373T>C
  • NM_001252634.2:c.1373T>C
  • NM_001354708.2:c.1373T>C
  • NM_001354709.2:c.1373T>C
  • NM_001354710.2:c.1373T>C
  • NM_001354711.2:c.1373T>C
  • NM_001354712.2:c.1373T>CMANE SELECT
  • NM_001354713.2:c.1373T>C
  • NM_001354714.2:c.1280T>C
  • NM_001354715.2:c.1280T>C
  • NP_000452.2:p.Val458Ala
  • NP_001121648.1:p.Val458Ala
  • NP_001121649.1:p.Val458Ala
  • NP_001239563.1:p.Val458Ala
  • NP_001341637.1:p.Val458Ala
  • NP_001341638.1:p.Val458Ala
  • NP_001341639.1:p.Val458Ala
  • NP_001341640.1:p.Val458Ala
  • NP_001341641.1:p.Val458Ala
  • NP_001341642.1:p.Val458Ala
  • NP_001341643.1:p.Val427Ala
  • NP_001341644.1:p.Val427Ala
  • NC_000003.11:g.24164388A>G
  • NM_000461.4:c.1373T>C
  • NM_001128177.1:c.1373T>C
Protein change:
V427A; VAL458ALA
Links:
OMIM: 190160.0035; dbSNP: rs121918704
NCBI 1000 Genomes Browser:
rs121918704
Molecular consequence:
  • NM_000461.5:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128176.3:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128177.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001252634.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354708.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354709.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354710.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354711.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354712.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354713.2:c.1373T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354714.2:c.1280T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354715.2:c.1280T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001134857Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Likely pathogenic
(Feb 25, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005324925GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely pathogenic
(Sep 18, 2023)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A new mutation in the thyroid hormone receptor (TR) beta gene (V458A) in a family with resistance to thyroid hormone (RTH).

Weiss RE, Tunca H, Gerstein HC, Refetoff S.

Thyroid. 1996 Aug;6(4):311-2. No abstract available.

PubMed [citation]
PMID:
8875752

A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone.

Lado-Abeal J, Dumitrescu AM, Liao XH, Cohen RN, Pohlenz J, Weiss RE, Lebrethon MC, Verloes A, Refetoff S.

J Clin Endocrinol Metab. 2005 Mar;90(3):1760-7. Epub 2004 Dec 14.

PubMed [citation]
PMID:
15598685
See all PubMed Citations (3)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134857.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Not found in the gnomAD exomes dataset, and the data is high quality (0/251490 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Located in potentially important domain of the protein. Two other pathogenic or likely pathogenic variants affect the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function.

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

From GeneDx, SCV005324925.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 8875752, 27537566, 30976996, 35738449, 15598685, 20237409, 26041374)

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

Last Updated: Oct 8, 2024