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NM_004387.4(NKX2-5):c.656C>T (p.Ala219Val) AND Tetralogy of Fallot

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 15, 2005
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:
RCV000009576.5

Allele description [Variation Report for NM_004387.4(NKX2-5):c.656C>T (p.Ala219Val)]

NM_004387.4(NKX2-5):c.656C>T (p.Ala219Val)

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.656C>T (p.Ala219Val)
HGVS:
  • NC_000005.10:g.173232888G>A
  • NG_013340.1:g.7425C>T
  • NM_001166175.2:c.*609C>T
  • NM_001166176.2:c.*455C>T
  • NM_004387.4:c.656C>TMANE SELECT
  • NP_004378.1:p.Ala219Val
  • LRG_671t1:c.656C>T
  • LRG_671:g.7425C>T
  • LRG_671p1:p.Ala219Val
  • NC_000005.9:g.172659891G>A
  • NM_004387.3:c.656C>T
  • P52952:p.Ala219Val
Protein change:
A219V; ALA219VAL
Links:
UniProtKB: P52952#VAR_038240; OMIM: 600584.0008; dbSNP: rs104893902
NCBI 1000 Genomes Browser:
rs104893902
Molecular consequence:
  • NM_001166175.2:c.*609C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001166176.2:c.*455C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_004387.4:c.656C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Tetralogy of Fallot (TOF)
Synonyms:
Fallot tetralogy
Identifiers:
MONDO: MONDO:0008542; MedGen: C0039685; Orphanet: 3303; OMIM: 187500; Human Phenotype Ontology: HP:0001636

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029794OMIM
no assertion criteria provided
Pathogenic
(Jul 15, 2005)
unknownliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

NKX2.5 mutations in patients with tetralogy of fallot.

Goldmuntz E, Geiger E, Benson DW.

Circulation. 2001 Nov 20;104(21):2565-8.

PubMed [citation]
PMID:
11714651

Functional dissection of sequence-specific NKX2-5 DNA binding domain mutations associated with human heart septation defects using a yeast-based system.

Inga A, Reamon-Buettner SM, Borlak J, Resnick MA.

Hum Mol Genet. 2005 Jul 15;14(14):1965-75. Epub 2005 May 25.

PubMed [citation]
PMID:
15917268

Details of each submission

From OMIM, SCV000029794.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Goldmuntz et al. (2001) reported an ala-to-val substitution at the highly conserved codon 219 position (A219V) of the CSX gene in an individual with tetralogy of Fallot (TOF; 187500) with pulmonary valve atresia without major aortopulmonary collateral arteries, right-sided aortic arch, and mirror-image aortic arch branching. The patient's mother was also found to carry this variant but was clinically normal. The authors concluded that this mutation was likely to represent a pathologic sequence change with reduced penetrance.

Inga et al. (2005) noted that the A219V mutation is located in the NK2-specific domain and showed that this mutation resulted in a mild reduction of function for all response elements tested using a yeast-based functional assay. They suggested that the germline A219V mutation is a risk factor that when combined with somatic NK2-5 mutations can increase the likelihood of congenital heart disease.

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

Last Updated: Sep 29, 2024