NM_004387.4(NKX2-5):c.355G>T (p.Ala119Ser) AND Hypothyroidism, congenital, nongoitrous, 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 1, 2006
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:: RCV000009584.5

Allele description [Variation Report for NM_004387.4(NKX2-5):c.355G>T (p.Ala119Ser)]

NM_004387.4(NKX2-5):c.355G>T (p.Ala119Ser)

Gene:

NKX2-5:NK2 homeobox 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.1

Genomic location:

Preferred name:

NM_004387.4(NKX2-5):c.355G>T (p.Ala119Ser)

Other names:

p.A119S:GCG>TCG

HGVS:

NC_000005.10:g.173233189C>A
NG_013340.1:g.7124G>T
NM_001166175.2:c.*308G>T
NM_001166176.2:c.*154G>T
NM_004387.4:c.355G>TMANE SELECT
NP_004378.1:p.Ala119Ser
LRG_671t1:c.355G>T
LRG_671:g.7124G>T
LRG_671p1:p.Ala119Ser
NC_000005.9:g.172660192C>A
NM_001166175.1:c.*308G>T
NM_004387.3:c.355G>T
P52952:p.Ala119Ser

Protein change:

A119S; ALA119SER

Links:

UniProtKB: P52952#VAR_047869; OMIM: 600584.0015; dbSNP: rs137852684

NCBI 1000 Genomes Browser:

rs137852684

Molecular consequence:

NM_001166175.2:c.*308G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001166176.2:c.*154G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_004387.4:c.355G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypothyroidism, congenital, nongoitrous, 5 (CHNG5)
Identifiers:: MONDO: MONDO:0009154; MedGen: C2673630; Orphanet: 95712; OMIM: 225250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029802	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029802

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2006)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis.

Dentice M, Cordeddu V, Rosica A, Ferrara AM, Santarpia L, Salvatore D, Chiovato L, Perri A, Moschini L, Fazzini C, Olivieri A, Costa P, Stoppioni V, Baserga M, De Felice M, Sorcini M, Fenzi G, Di Lauro R, Tartaglia M, Macchia PE.

J Clin Endocrinol Metab. 2006 Apr;91(4):1428-33. Epub 2006 Jan 17.

PubMed [citation]

PMID:: 16418214

Details of each submission

From OMIM, SCV000029802.3

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

Description

In a 13-year-old girl with an ectopic thyroid and severe hypothyroidism (CHNG5; 225250), who had no documented congenital heart defect, Dentice et al. (2006) identified a heterozygous 335G-T transversion in the NXK2E gene, resulting in an ala119-to-ser substitution a few residues upstream from the beginning of the homeodomain. The mutation was inherited from the mother, who exhibited autoimmune hypothyroidism and was on lifelong treatment with L-T4, and was not observed among 561 controls. The mutation exhibited a significant functional impairment, with reduction of transactivation properties and dominant-negative effect, which was associated with reduced DNA binding.

#	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

Last Updated: Oct 20, 2024

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