NM_000238.4(KCNH2):c.568G>A (p.Ala190Thr) AND not specified

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Mar 3, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000780360.4

Allele description [Variation Report for NM_000238.4(KCNH2):c.568G>A (p.Ala190Thr)]

NM_000238.4(KCNH2):c.568G>A (p.Ala190Thr)

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.568G>A (p.Ala190Thr)

HGVS:

NC_000007.14:g.150958407C>T
NG_008916.1:g.24520G>A
NM_000238.4:c.568G>AMANE SELECT
NM_001406753.1:c.280G>A
NM_001406755.1:c.391G>A
NM_001406756.1:c.280G>A
NM_001406757.1:c.268G>A
NM_172056.3:c.568G>A
NP_000229.1:p.Ala190Thr
NP_000229.1:p.Ala190Thr
NP_001393682.1:p.Ala94Thr
NP_001393684.1:p.Ala131Thr
NP_001393685.1:p.Ala94Thr
NP_001393686.1:p.Ala90Thr
NP_742053.1:p.Ala190Thr
NP_742053.1:p.Ala190Thr
LRG_288t1:c.568G>A
LRG_288t2:c.568G>A
LRG_288:g.24520G>A
LRG_288p1:p.Ala190Thr
LRG_288p2:p.Ala190Thr
NC_000007.13:g.150655495C>T
NM_000238.3:c.568G>A
NM_172056.2:c.568G>A
NR_176254.1:n.976G>A

Protein change:

A131T

Links:

dbSNP: rs150817714

NCBI 1000 Genomes Browser:

rs150817714

Molecular consequence:

NM_000238.4:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.268G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000917553	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 6, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14661677, 25649125 Citation Link,
SCV001433429	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Mar 3, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000917553

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 6, 2018)

germline

clinical testing

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

Citation Link,

SCV001433429

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Mar 3, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.

Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME.

Mayo Clin Proc. 2003 Dec;78(12):1479-87.

PubMed [citation]

PMID:: 14661677

Bayesian models for syndrome- and gene-specific probabilities of novel variant pathogenicity.

Ruklisa D, Ware JS, Walsh R, Balding DJ, Cook SA.

Genome Med. 2015;7(1):5. doi: 10.1186/s13073-014-0120-4.

PubMed [citation]

PMID:: 25649125
PMCID:: PMC4308924

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917553.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: KCNH2 c.568G>A (p.Ala190Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was observed with an allele frequency of 0.00085 in 31934 control chromosomes (gnomAD and publication controls). The observed variant frequency within African control individuals in the gnomAD database is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNH2 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.568G>A, has been reported in the literature in individuals affected with Arrhythmia. These report(s) do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as benign.

#	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

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV001433429.1

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

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

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine