NM_000238.4(KCNH2):c.2680C>T (p.Arg894Cys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 8, 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:: RCV003162446.8

Allele description [Variation Report for NM_000238.4(KCNH2):c.2680C>T (p.Arg894Cys)]

NM_000238.4(KCNH2):c.2680C>T (p.Arg894Cys)

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.2680C>T (p.Arg894Cys)

Other names:

p.R894C:CGC>TGC

HGVS:

NC_000007.14:g.150948456G>A
NG_008916.1:g.34471C>T
NM_000238.4:c.2680C>TMANE SELECT
NM_001406753.1:c.2392C>T
NM_172057.3:c.1660C>T
NP_000229.1:p.Arg894Cys
NP_000229.1:p.Arg894Cys
NP_001393682.1:p.Arg798Cys
NP_742054.1:p.Arg554Cys
NP_742054.1:p.Arg554Cys
LRG_288t1:c.2680C>T
LRG_288t3:c.1660C>T
LRG_288:g.34471C>T
LRG_288p1:p.Arg894Cys
LRG_288p3:p.Arg554Cys
NC_000007.13:g.150645544G>A
NM_000238.2:c.2680C>T
NM_000238.3:c.2680C>T
NM_172056.1:c.*1443C>T
NM_172057.2:c.1660C>T
NR_176254.1:n.3088C>T
NR_176255.1:n.1961C>T
Q12809:p.Arg894Cys

Protein change:

R554C

Links:

UniProtKB: Q12809#VAR_074887; dbSNP: rs199473433

NCBI 1000 Genomes Browser:

rs199473433

Molecular consequence:

NM_000238.4:c.2680C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.2392C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1660C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_176254.1:n.3088C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176255.1:n.1961C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003900765	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Feb 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19716085, 24631775, 28532774 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003900765

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Feb 8, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths.

Wang D, Shah KR, Um SY, Eng LS, Zhou B, Lin Y, Mitchell AA, Nicaj L, Prinz M, McDonald TV, Sampson BA, Tang Y.

Forensic Sci Int. 2014 Apr;237:90-9. doi: 10.1016/j.forsciint.2014.01.014. Epub 2014 Feb 15.

PubMed [citation]

PMID:: 24631775

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003900765.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.R894C variant (also known as c.2680C>T), located in coding exon 11 of the KCNH2 gene, results from a C to T substitution at nucleotide position 2680. The arginine at codon 894 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in long QT syndrome cohorts and a sudden unexplained death cohort; however clinical details were limited in some cases (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; Wang D et al. Forensic Sci Int, 2014 Apr;237:90-9; Ebrahim MA et al. Am J Cardiol, 2017 Jul;120:256-261). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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