NM_003235.5(TG):c.2359C>T (p.Arg787Ter) AND Iodotyrosyl coupling defect

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 1, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000778925.9

Allele description [Variation Report for NM_003235.5(TG):c.2359C>T (p.Arg787Ter)]

NM_003235.5(TG):c.2359C>T (p.Arg787Ter)

Gene:

TG:thyroglobulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.22

Genomic location:

Preferred name:

NM_003235.5(TG):c.2359C>T (p.Arg787Ter)

HGVS:

NC_000008.11:g.132888166C>T
NG_015832.1:g.26207C>T
NM_003235.5:c.2359C>TMANE SELECT
NP_003226.4:p.Arg787Ter
NC_000008.10:g.133900411C>T
NM_003235.4:c.2359C>T

Protein change:

R787*

Links:

dbSNP: rs752966476

NCBI 1000 Genomes Browser:

rs752966476

Molecular consequence:

NM_003235.5:c.2359C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Iodotyrosyl coupling defect (TDH3)
Synonyms:: HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 3; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 3
Identifiers:: MONDO: MONDO:0010135; MedGen: C0342194; Orphanet: 95716; OMIM: 274700

Recent activity

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Danio rerio F-box protein 30a (fbxo30a), mRNA
Danio rerio F-box protein 30a (fbxo30a), mRNA
gi|41055928|ref|NM_201151.1|

Nucleotide
cyclic pyranopterin monophosphate synthase accessory protein [Mycobacterium tube...
cyclic pyranopterin monophosphate synthase accessory protein [Mycobacterium tuberculosis H37Rv]
gi|15608004|ref|NP_215379.1|

Protein
PREDICTED: Mus musculus predicted gene, 40802 (Gm40802), ncRNA
PREDICTED: Mus musculus predicted gene, 40802 (Gm40802), ncRNA
gi|1720363451|ref|XR_872173.2|

Nucleotide
fliG [Aquifex aeolicus VF5]
fliG [Aquifex aeolicus VF5]
Gene ID:1193953

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000915340	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23164529, 17033963, 23455760 Citation Link,
SCV002515371	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2022)	maternal	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 36474027

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000915340

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV002515371

Daryl Scott Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2022)

maternal

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New insights into thyroglobulin gene: molecular analysis of seven novel mutations associated with goiter and hypothyroidism.

Citterio CE, Machiavelli GA, Miras MB, Gruñeiro-Papendieck L, Lachlan K, Sobrero G, Chiesa A, Walker J, Muñoz L, Testa G, Belforte FS, González-Sarmiento R, Rivolta CM, Targovnik HM.

Mol Cell Endocrinol. 2013 Jan 30;365(2):277-91. doi: 10.1016/j.mce.2012.11.002. Epub 2012 Nov 16.

PubMed [citation]

PMID:: 23164529

Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs.

Smeitink JA, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P, Sasarman F, Vriend G, Jacob-Hirsch J, Shaag A, Rechavi G, Welling B, Horst J, Rodenburg RJ, van den Heuvel B, Shoubridge EA.

Am J Hum Genet. 2006 Nov;79(5):869-77. Epub 2006 Sep 15.

PubMed [citation]

PMID:: 17033963
PMCID:: PMC1698578

See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915340.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The TG c.2359C>T (p.Arg787Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Arg787Ter variant has been reported in two studies in which it is found in a total of four patients with thyroid dyshormonogenesis, including in two siblings in a homozygous state, and in two siblings in a heterozygous state with no second variant identified. The variant was also found in a heterozygous state in the unaffected fathers in both families (Agretti et al. 2013; Citterio et al. 2013). The p.Arg787Ter variant was absent from 60 controls and is reported at a frequency of 0.00003 in the total population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Arg787Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for thyroid dyshormonogenesis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

From Daryl Scott Lab, Baylor College of Medicine, SCV002515371.1

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

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

Last Updated: Jul 29, 2024

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