NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 20, 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:: RCV001841705.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val)]

NM_000238.4(KCNH2):c.2131A>G (p.Ile711Val)

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.2131A>G (p.Ile711Val)

Other names:

p.I711V:ATC>GTC

HGVS:

NC_000007.14:g.150950935T>C
NG_008916.1:g.31992A>G
NM_000238.4:c.2131A>GMANE SELECT
NM_001204798.2:c.1111A>G
NM_001406753.1:c.1843A>G
NM_001406755.1:c.1954A>G
NM_001406756.1:c.1843A>G
NM_001406757.1:c.1831A>G
NM_172056.3:c.2131A>G
NM_172057.3:c.1111A>G
NP_000229.1:p.Ile711Val
NP_000229.1:p.Ile711Val
NP_001191727.1:p.Ile371Val
NP_001393682.1:p.Ile615Val
NP_001393684.1:p.Ile652Val
NP_001393685.1:p.Ile615Val
NP_001393686.1:p.Ile611Val
NP_742053.1:p.Ile711Val
NP_742053.1:p.Ile711Val
NP_742054.1:p.Ile371Val
NP_742054.1:p.Ile371Val
LRG_288t1:c.2131A>G
LRG_288t2:c.2131A>G
LRG_288t3:c.1111A>G
LRG_288:g.31992A>G
LRG_288p1:p.Ile711Val
LRG_288p2:p.Ile711Val
LRG_288p3:p.Ile371Val
NC_000007.13:g.150648023T>C
NM_000238.2:c.2131A>G
NM_000238.3:c.2131A>G
NM_172056.2:c.2131A>G
NM_172057.2:c.1111A>G
NR_176254.1:n.2539A>G
NR_176255.1:n.1412A>G
Q12809:p.Ile711Val

Protein change:

I371V

Links:

UniProtKB: Q12809#VAR_074871; dbSNP: rs199473532

NCBI 1000 Genomes Browser:

rs199473532

Molecular consequence:

NM_000238.4:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.1111A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1843A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1954A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1843A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1831A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1111A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000913629	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19716085, 25417810, 27807201, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000913629

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 20, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome.

Anderson CL, Kuzmicki CE, Childs RR, Hintz CJ, Delisle BP, January CT.

Nat Commun. 2014 Nov 24;5:5535. doi: 10.1038/ncomms6535.

PubMed [citation]

PMID:: 25417810
PMCID:: PMC4243539

See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913629.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces isoleucine with valine at codon 711 of the KCNH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant may affect channel gating (PMID: 25417810, 27807201). This variant has been reported in an individual suspected of having long QT syndrome (PMID: 19716085). This variant has been identified in 9/251380 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.

#	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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