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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 21, 2019
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:: RCV002362574.2

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:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

TSA: Tetralonia malvae s7577_L_18360_0_a_3_6_l_1119 transcribed RNA sequence
TSA: Tetralonia malvae s7577_L_18360_0_a_3_6_l_1119 transcribed RNA sequence
gi|1163965014|gb|GBNI01029296.1||gn :GBNI01|s7577_L_18360_0_a_3_6_l_1119

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002664807	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 21, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11714651, 15161646, 15917268 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002664807

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 21, 2019)

germline

clinical testing

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

Citation Link

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

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

Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac malformations.

Reamon-Buettner SM, Hecker H, Spanel-Borowski K, Craatz S, Kuenzel E, Borlak J.

Am J Pathol. 2004 Jun;164(6):2117-25.

PubMed [citation]

PMID:: 15161646
PMCID:: PMC1615780

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002664807.2

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

Description

The p.A219V variant (also known as c.656C>T), located in coding exon 2 of the NKX2-5 gene, results from a C to T substitution at nucleotide position 656. The alanine at codon 219 is replaced by valine, an amino acid with similar properties. This variant has been detected in a proband with tetralogy of Fallot and an in an unaffected parent (Goldmuntz E et al. Circulation, 2001 Nov;104:2565-8). This variant has also been detected in probands with ventricular septal defect; however, some cases also had an additional NKX2-5 variant (Reamon-Buettner SM et al. Am. J. Pathol., 2004 Jun;164:2117-25). A yeast assay reported this variant may have mild impact on function (Inga A et al. Hum. Mol. Genet., 2005 Jul;14:1965-75). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

ClinVar

Relating variation to medicine