VCV000012571.2 - ClinVar

NM_001354712.2(THRB):c.1305dup (p.Ala436fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001354712.2(THRB):c.1305dup (p.Ala436fs)

Variation ID: 12571 Accession: VCV000012571.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: 3p24.2 3: 24122964-24122965 (GRCh38) [ NCBI UCSC ] 3: 24164455-24164456 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 17, 2021	Jan 17, 2021	May 1, 2006

HGVS

Nucleotide	Protein	Molecular consequence
NM_001354712.2:c.1305dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001341641.1:p.Ala436fs	frameshift
NM_000461.5:c.1305dup	NP_000452.2:p.Ala436fs	frameshift
NM_001128176.3:c.1305dup	NP_001121648.1:p.Ala436fs	frameshift
NM_001128177.2:c.1305dup	NP_001121649.1:p.Ala436fs	frameshift
NM_001252634.2:c.1305dup	NP_001239563.1:p.Ala436fs	frameshift
NM_001354708.2:c.1305dup	NP_001341637.1:p.Ala436fs	frameshift
NM_001354709.2:c.1305dup	NP_001341638.1:p.Ala436fs	frameshift
NM_001354710.2:c.1305dup	NP_001341639.1:p.Ala436fs	frameshift
NM_001354711.2:c.1305dup	NP_001341640.1:p.Ala436fs	frameshift
NM_001354713.2:c.1305dup	NP_001341642.1:p.Ala436fs	frameshift
NM_001354714.2:c.1212dup	NP_001341643.1:p.Ala405fs	frameshift
NM_001354715.2:c.1212dup	NP_001341644.1:p.Ala405fs	frameshift
NM_001374822.1:c.1305dup	NP_001361751.1:p.Ala436fs	frameshift
NM_001374823.1:c.1305dup	NP_001361752.1:p.Ala436fs	frameshift
NM_001374824.1:c.1305dup	NP_001361753.1:p.Ala436fs	frameshift
NM_001374825.1:c.1305dup	NP_001361754.1:p.Ala436fs	frameshift
NM_001374826.1:c.1305dup	NP_001361755.1:p.Ala436fs	frameshift
NM_001374827.1:c.1134dup	NP_001361756.1:p.Ala379fs	frameshift
NC_000003.12:g.24122965dup
NC_000003.11:g.24164456dup
NG_009159.1:g.376858dup

... more HGVS ... less HGVS

Protein change

A436fs, A379fs, A405fs

Other names

Canonical SPDI

NC_000003.12:24122964:A:AA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 190160.0042 VarSome

Comment on variant

NCBI staff provided HGVS expressions for allelic variant 190160.0042 based the sequence in Figure 2 and the altered protein sequence reported in the paper by Wu et al., 2006 (PubMed 16464943).

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
THRB		-	-	GRCh38 GRCh37	323	367

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Selective pituitary resistance to thyroid hormone	Pathogenic (1)	no assertion criteria provided	May 1, 2006	RCV000013399.26

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 01, 2006)	no assertion criteria provided Method: literature only	THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY Affected status: not provided Allele origin: germline	OMIM Accession: SCV000033646.3 First in ClinVar: Apr 04, 2013 Last updated: Jan 17, 2021	Publications: PubMed (1) PubMed: 16464943 Comment on evidence: Wu et al. (2006) reported a newborn Turkish male, the child of nonconsanguineous parents, with severe but predominantly pituitary thyroid hormone resistance (PRTH; 145650) who … (more) Wu et al. (2006) reported a newborn Turkish male, the child of nonconsanguineous parents, with severe but predominantly pituitary thyroid hormone resistance (PRTH; 145650) who presented at 6 days of age with respiratory distress, tachycardia, diaphoresis, and a thyroid gland 4 times normal size. The authors hypothesized that the RTH was due to reduced ligand binding and/or abnormal interaction with nuclear cofactors. Sequencing of the THRB gene demonstrated a de novo heterozygous mutation, 1590_1591insT, resulting in a frameshift producing a mutant THR-beta with a 28-amino acid nonsense sequence and 2-amino acid carboxyl-terminal extension. The mutant TR-beta had impaired ability to recruit nuclear receptor corepressor (NCOR1; 600849) but intact association with silencing mediator of retinoid and thyroid receptor (SMRT; 600848). Wu et al. (2006) concluded that alterations in codons 436-453 in helix 11 of THR-beta result in significantly diminished association with NCOR but not with SMRT. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A novel thyroid hormone receptor-beta mutation that fails to bind nuclear receptor corepressor in a patient as an apparent cause of severe, predominantly pituitary resistance to thyroid hormone.	Wu SY	The Journal of clinical endocrinology and metabolism	2006	PMID: 16464943

Text-mined citations for this variant ...

Record last updated Nov 29, 2022

ClinVar Genomic variation as it relates to human health

NM_001354712.2(THRB):c.1305dup (p.Ala436fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...