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NM_000238.4(KCNH2):c.2350C>T (p.Arg784Trp) AND Long QT syndrome 2, acquired, susceptibility to

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 23, 2002
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:
RCV000015514.12

Allele description

NM_000238.4(KCNH2):c.2350C>T (p.Arg784Trp)

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.2350C>T (p.Arg784Trp)
HGVS:
  • NC_000007.14:g.150950216G>A
  • NG_008916.1:g.32711C>T
  • NM_000238.4:c.2350C>TMANE SELECT
  • NM_001204798.2:c.1330C>T
  • NM_001406753.1:c.2062C>T
  • NM_001406755.1:c.2173C>T
  • NM_001406756.1:c.2062C>T
  • NM_001406757.1:c.2050C>T
  • NM_172056.3:c.2350C>T
  • NM_172057.3:c.1330C>T
  • NP_000229.1:p.Arg784Trp
  • NP_000229.1:p.Arg784Trp
  • NP_001191727.1:p.Arg444Trp
  • NP_001393682.1:p.Arg688Trp
  • NP_001393684.1:p.Arg725Trp
  • NP_001393685.1:p.Arg688Trp
  • NP_001393686.1:p.Arg684Trp
  • NP_742053.1:p.Arg784Trp
  • NP_742053.1:p.Arg784Trp
  • NP_742054.1:p.Arg444Trp
  • NP_742054.1:p.Arg444Trp
  • LRG_288t1:c.2350C>T
  • LRG_288t2:c.2350C>T
  • LRG_288t3:c.1330C>T
  • LRG_288:g.32711C>T
  • LRG_288p1:p.Arg784Trp
  • LRG_288p2:p.Arg784Trp
  • LRG_288p3:p.Arg444Trp
  • NC_000007.13:g.150647304G>A
  • NM_000238.3:c.2350C>T
  • NM_172056.2:c.2350C>T
  • NM_172057.2:c.1330C>T
  • NR_176254.1:n.2758C>T
  • NR_176255.1:n.1631C>T
  • Q12809:p.Arg784Trp
Protein change:
R444W; ARG784TRP
Links:
UniProtKB: Q12809#VAR_036676; OMIM: 152427.0014; dbSNP: rs12720441
NCBI 1000 Genomes Browser:
rs12720441
Molecular consequence:
  • NM_000238.4:c.2350C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.1330C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.2062C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.2173C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.2062C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.2050C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.2350C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.1330C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 2, acquired, susceptibility to
Identifiers:
MedGen: CN070020

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000035779OMIM
no assertion criteria provided
Uncertain significance
(Apr 23, 2002) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes.

Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, Hohnloser SH, Shimizu W, Schwartz PJ, Stanton M, Murray KT, Norris K, George AL Jr, Roden DM.

Circulation. 2002 Apr 23;105(16):1943-8.

PubMed [citation]
PMID:
11997281

Genetic variants associated with inherited cardiovascular disorders among 13,131 asymptomatic older adults of European descent.

Lacaze P, Sebra R, Riaz M, Ingles J, Tiller J, Thompson BA, James PA, Fatkin D, Semsarian C, Reid CM, Tonkin AM, Winship I, Schadt E, McNeil JJ.

NPJ Genom Med. 2021 Jun 16;6(1):51. doi: 10.1038/s41525-021-00211-x.

PubMed [citation]
PMID:
34135346
PMCID:
PMC8209162

Details of each submission

From OMIM, SCV000035779.3

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

Description

This variant, formerly titled LONG QT SYNDROME 2, ACQUIRED, SUSCEPTIBILITY TO, has been reclassified based on the article by Lacaze et al. (2021).

Yang et al. (2002) described an individual who developed QT prolongation and torsade de pointes while taking the drug amiodarone (see 613688). The ECG abnormalities reversed on drug withdrawal. Analysis of the coding sequence of the gene encoding HERG revealed a C-to-T transition at nucleotide position 2350, which resulted in an arginine-to-tryptophan substitution at amino acid position 784 (R784W). The mutation was not found in 228 controls. In vitro expression studies of the mutant protein confirmed a significant reduction in potassium currents. These findings suggested that the R784W mutation was responsible for the patient's response to amiodarone.

In a review of genetic variants associated with inherited cardiovascular disorders among 13,131 asymptomatic older adults (mean age, 75 years) of European descent, Lacaze et al. (2021) identified the R784W variant in 3 alleles, thus calling its pathogenicity into question.

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

Last Updated: Sep 29, 2024