NM_001206744.2(TPO):c.2421del (p.Cys808fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 21, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003558563.2

Allele description [Variation Report for NM_001206744.2(TPO):c.2421del (p.Cys808fs)]

NM_001206744.2(TPO):c.2421del (p.Cys808fs)

Gene:

TPO:thyroid peroxidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p25.3

Genomic location:

Preferred name:

NM_001206744.2(TPO):c.2421del (p.Cys808fs)

HGVS:

NC_000002.12:g.1503982del
NG_011581.1:g.95520del
NM_000547.6:c.2421del
NM_001206744.2:c.2421delMANE SELECT
NM_001206745.2:c.2250del
NM_175719.4:c.2250del
NM_175721.3:c.2386+7217del
NM_175722.3:c.1902del
NP_000538.3:p.Cys808fs
NP_000538.3:p.Cys808fs
NP_001193673.1:p.Cys808fs
NP_001193674.1:p.Cys751fs
NP_783650.1:p.Cys751fs
NP_783653.1:p.Cys635fs
NC_000002.11:g.1507748del
NC_000002.11:g.1507754del
NM_000547.5:c.2421del

Protein change:

C635fs

Links:

dbSNP: rs760307139

NCBI 1000 Genomes Browser:

rs760307139

Molecular consequence:

NM_000547.6:c.2421del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206744.2:c.2421del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206745.2:c.2250del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_175719.4:c.2250del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_175722.3:c.1902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_175721.3:c.2386+7217del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292054	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 21, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11061528, 23236987, 25564141, 27135621, 34200080, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292054

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 21, 2023)

germline

clinical testing

PubMed (6)
[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

Citations

PubMed

Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update).

Bakker B, Bikker H, Vulsma T, de Randamie JS, Wiedijk BM, De Vijlder JJ.

J Clin Endocrinol Metab. 2000 Oct;85(10):3708-12.

PubMed [citation]

PMID:: 11061528

Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community.

Cangul H, Aycan Z, Olivera-Nappa A, Saglam H, Schoenmakers NA, Boelaert K, Cetinkaya S, Tarim O, Bober E, Darendeliler F, Bas V, Demir K, Aydin BK, Kendall M, Cole T, Högler W, Chatterjee VK, Barrett TG, Maher ER.

Clin Endocrinol (Oxf). 2013 Aug;79(2):275-81. doi: 10.1111/cen.12127. Epub 2013 May 6.

PubMed [citation]

PMID:: 23236987

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292054.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Cys808Alafs*24) in the TPO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPO are known to be pathogenic (PMID: 11061528, 23236987, 25564141). This variant is present in population databases (rs760307139, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with congenital hypothyroidism (PMID: 27135621, 34200080). ClinVar contains an entry for this variant (Variation ID: 623380). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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