U.S. flag

An official website of the United States government

NM_000238.4(KCNH2):c.2371C>T (p.Arg791Trp) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Feb 5, 2024
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:
RCV002228167.10

Allele description [Variation Report for NM_000238.4(KCNH2):c.2371C>T (p.Arg791Trp)]

NM_000238.4(KCNH2):c.2371C>T (p.Arg791Trp)

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.2371C>T (p.Arg791Trp)
Other names:
p.R791W:CGG>TGG
HGVS:
  • NC_000007.14:g.150950195G>A
  • NG_008916.1:g.32732C>T
  • NM_000238.4:c.2371C>TMANE SELECT
  • NM_001204798.2:c.1351C>T
  • NM_001406753.1:c.2083C>T
  • NM_001406755.1:c.2194C>T
  • NM_001406756.1:c.2083C>T
  • NM_001406757.1:c.2071C>T
  • NM_172056.3:c.2371C>T
  • NM_172057.3:c.1351C>T
  • NP_000229.1:p.Arg791Trp
  • NP_000229.1:p.Arg791Trp
  • NP_001191727.1:p.Arg451Trp
  • NP_001393682.1:p.Arg695Trp
  • NP_001393684.1:p.Arg732Trp
  • NP_001393685.1:p.Arg695Trp
  • NP_001393686.1:p.Arg691Trp
  • NP_742053.1:p.Arg791Trp
  • NP_742053.1:p.Arg791Trp
  • NP_742054.1:p.Arg451Trp
  • NP_742054.1:p.Arg451Trp
  • LRG_288t1:c.2371C>T
  • LRG_288t2:c.2371C>T
  • LRG_288t3:c.1351C>T
  • LRG_288:g.32732C>T
  • LRG_288p1:p.Arg791Trp
  • LRG_288p2:p.Arg791Trp
  • LRG_288p3:p.Arg451Trp
  • NC_000007.13:g.150647283G>A
  • NM_000238.2:c.2371C>T
  • NM_000238.3:c.2371C>T
  • NM_172056.2:c.2371C>T
  • NM_172057.2:c.1351C>T
  • NR_176254.1:n.2779C>T
  • NR_176255.1:n.1652C>T
  • Q12809:p.Arg791Trp
Protein change:
R451W
Links:
UniProtKB: Q12809#VAR_074879; dbSNP: rs138498207
NCBI 1000 Genomes Browser:
rs138498207
Molecular consequence:
  • NM_000238.4:c.2371C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.1351C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.2083C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.2194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.2083C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.2071C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.2371C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.1351C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
variation affecting protein function [Variation Ontology: 0003]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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
SCV000696024Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Feb 5, 2024) 		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

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]
PMID:
19716085
PMCID:
PMC3049907

Identification of Medically Actionable Secondary Findings in the 1000 Genomes.

Olfson E, Cottrell CE, Davidson NO, Gurnett CA, Heusel JW, Stitziel NO, Chen LS, Hartz S, Nagarajan R, Saccone NL, Bierut LJ.

PLoS One. 2015;10(9):e0135193. doi: 10.1371/journal.pone.0135193.

PubMed [citation]
PMID:
26332594
PMCID:
PMC4558085
See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696024.3

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

Description

Variant summary: KCNH2 c.2371C>T (p.Arg791Trp) results in a non-conservative amino acid change located in the Cyclic nucleotide-binding domain (IPR000595) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.9e-05 in 281704 control chromosomes, predominantly at a frequency of 0.00093 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 8 fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNH2 causing Long QT Syndrome phenotype (0.00012), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.2371C>T has been reported in the literature in individuals affected with Long QT Syndrome and sudden infant death syndrome (Kapplinger_2009, Smith_2018), however without strong evidence for causality (e.g., lack of co-segregation data). These reports therefore do not provide unequivocal conclusions about association of the variant with Long QT Syndrome. One functional study showed this variant with competent trafficking and moderate alteration on gating (Anderson_2014) with nearly normal values for the repolarizing outward potassium current density or Ikv11.1. Another functional study demonstrated this variant expressed and generated peak Kv11.1 current levels similar to cells expressing wild-type-Kv11.1 channels but altered gating (Smith_2018). The following publications have been ascertained in the context of this evaluation (PMID: 25637381, 25417810, 32048431, 19716085, 29247119, 26332594, 29752375). ClinVar contains an entry for this variant (Variation ID: 67391). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Aug 25, 2024