U.S. flag

An official website of the United States government

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

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 1, 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:
RCV001841245.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.2350C>T (p.Arg784Trp)]

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:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001348997Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 1, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

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

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]
PMID:
15840476
See all PubMed Citations (8)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001348997.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This missense variant replaces arginine with tryptophan at codon 784 of the KCNH2 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). In vitro experimental functional studies have shown that this variant may result in deficient protein trafficking (PMID: 25417810), reduced channel current (PMID: 11997281) and faster channel deactivation compared to wild type (PMID: 19172259). This variant has been reported in two individuals affected with long QT syndrome (PMID: 19841300, 22949429) and in an individual suspected to be affected with long QT syndrome (PMID: 15840476). This variant has also been reported in two individuals affected with drug-induced torsades de pointes, a form of ventricular tachycardia (PMID: 11997281, 24223155). This variant has been identified in 3/282186 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 26, 2024