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NM_004387.4(NKX2-5):c.848C>A (p.Pro283Gln) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 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:
RCV002408478.2

Allele description [Variation Report for NM_004387.4(NKX2-5):c.848C>A (p.Pro283Gln)]

NM_004387.4(NKX2-5):c.848C>A (p.Pro283Gln)

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.848C>A (p.Pro283Gln)
HGVS:
  • NC_000005.10:g.173232696G>T
  • NG_013340.1:g.7617C>A
  • NM_001166175.2:c.*801C>A
  • NM_001166176.2:c.*647C>A
  • NM_004387.4:c.848C>AMANE SELECT
  • NP_004378.1:p.Pro283Gln
  • LRG_671t1:c.848C>A
  • LRG_671:g.7617C>A
  • LRG_671p1:p.Pro283Gln
  • NC_000005.9:g.172659699G>T
  • NM_004387.3:c.848C>A
  • P52952:p.Pro283Gln
Protein change:
P283Q; PRO283GLN
Links:
UniProtKB: P52952#VAR_067587; OMIM: 600584.0021; dbSNP: rs375086983
NCBI 1000 Genomes Browser:
rs375086983
Molecular consequence:
  • NM_001166175.2:c.*801C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001166176.2:c.*647C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_004387.4:c.848C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002675366Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 18, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease.

Peng T, Wang L, Zhou SF, Li X.

Genetica. 2010 Dec;138(11-12):1231-40. doi: 10.1007/s10709-010-9522-4. Epub 2010 Nov 26.

PubMed [citation]
PMID:
21110066

NKX2-5 mutations in an inbred consanguineous population: genetic and phenotypic diversity.

Abou Hassan OK, Fahed AC, Batrawi M, Arabi M, Refaat MM, DePalma SR, Seidman JG, Seidman CE, Bitar FF, Nemer GM.

Sci Rep. 2015 Mar 6;5:8848. doi: 10.1038/srep08848.

PubMed [citation]
PMID:
25742962
PMCID:
PMC4351524
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002675366.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.P283Q variant (also known as c.848C>A), located in coding exon 2 of the NKX2-5 gene, results from a C to A substitution at nucleotide position 848. The proline at codon 283 is replaced by glutamine, an amino acid with similar properties. This alteration has been reported in individuals with ventricular septal defect, patent ductus arteriosus and aortic stenosis (Peng T et al. Genetica, 2010 Dec;138:1231-40; Abou Hassan OK et al. Sci Rep. 2015 Mar;5:8848). This variant was also reported in one individual from a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This variant has also been detected in congenital hypothyroidism cohorts, where some cases had additional genetic variants also detected (Fu C et al. Clin. Chim. Acta, 2019 Feb;489:103-108; Wang F et al. Front Endocrinol (Lausanne), 2020 Apr;11:237). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024