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NM_000238.4(KCNH2):c.3140G>T (p.Arg1047Leu) AND Sudden unexplained death

Germline classification:
Likely benign (1 submission)
Last evaluated:
Mar 27, 2015
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:
RCV000172896.10

Allele description [Variation Report for NM_000238.4(KCNH2):c.3140G>T (p.Arg1047Leu)]

NM_000238.4(KCNH2):c.3140G>T (p.Arg1047Leu)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.3140G>T (p.Arg1047Leu)
HGVS:
  • NC_000007.14:g.150947340C>A
  • NG_008916.1:g.35587G>T
  • NM_000238.4:c.3140G>TMANE SELECT
  • NM_172057.3:c.2120G>T
  • NP_000229.1:p.Arg1047Leu
  • NP_000229.1:p.Arg1047Leu
  • NP_742054.1:p.Arg707Leu
  • LRG_288t1:c.3140G>T
  • LRG_288:g.35587G>T
  • LRG_288p1:p.Arg1047Leu
  • NC_000007.13:g.150644428C>A
  • NM_000238.2:c.3140G>T
  • NM_000238.3:c.3140G>T
Protein change:
R1047L
Links:
dbSNP: rs36210421
NCBI 1000 Genomes Browser:
rs36210421
Molecular consequence:
  • NM_000238.4:c.3140G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.2120G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sudden unexplained death
Identifiers:
MedGen: C0520806

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000223887Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
criteria provided, single submitter

(Agnes Ginges Centre for Molecular Cardiology criteria (2015))		Likely benign
(Mar 27, 2015) 		germlineresearch

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot provided1not providednot providednot providedresearch

Citations

PubMed

Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced Torsades de Pointes.

Sun Z, Milos PM, Thompson JF, Lloyd DB, Mank-Seymour A, Richmond J, Cordes JS, Zhou J.

J Mol Cell Cardiol. 2004 Nov;37(5):1031-9.

PubMed [citation]
PMID:
15522280

Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ.

Circulation. 2009 Nov 3;120(18):1752-60. doi: 10.1161/CIRCULATIONAHA.109.863076. Epub 2009 Oct 19.

PubMed [citation]
PMID:
19841300
PMCID:
PMC3025752
See all PubMed Citations (3)

Details of each submission

From Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV000223887.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (3)

Description

The KCNH2 Arg1047Leu variant has previously been reported as a polymorphism and suggested to be associated with increased risk to Torsades de Pointes (Mank-Seymour AR et al., 2006; Sun Z et al., 2004; Kapa S et al., 2009). It is present in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/) with an allele frequency of 0.008 (105/11944 alleles); and the frequency in the European (non-Finnish) sub-population is 0.02 (73/3656 alleles). We identified this variant in a 16 yo boy who had a sudden cardiac arrest with no pre-morbid diagnosis and Greek ethnicity. Post-mortem examination was unremarkable and there is no family history of any cardiac disease. Based on the frequency of the KCNH2 Arg1047Leu variant in 2% of the European (non-Finnish) population, we do not expect this variant to cause disease in isolation. We therefore classify this variant as "likely benign".

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot provided1not provided

Last Updated: Oct 8, 2024