U.S. flag

An official website of the United States government

NM_000238.4(KCNH2):c.2510A>G (p.Asp837Gly) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 22, 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:
RCV002433554.9

Allele description [Variation Report for NM_000238.4(KCNH2):c.2510A>G (p.Asp837Gly)]

NM_000238.4(KCNH2):c.2510A>G (p.Asp837Gly)

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.2510A>G (p.Asp837Gly)
Other names:
p.D837G:GAC>GGC; NM_000238.3(KCNH2):c.2510A>G(p.Asp837Gly); NM_172057.2(KCNH2):c.1490A>G(p.Asp497Gly)
HGVS:
  • NC_000007.14:g.150948938T>C
  • NG_008916.1:g.33989A>G
  • NM_000238.4:c.2510A>GMANE SELECT
  • NM_172057.3:c.1490A>G
  • NP_000229.1:p.Asp837Gly
  • NP_000229.1:p.Asp837Gly
  • NP_742054.1:p.Asp497Gly
  • LRG_288t1:c.2510A>G
  • LRG_288:g.33989A>G
  • LRG_288p1:p.Asp837Gly
  • NC_000007.13:g.150646026T>C
  • NM_000238.2:c.2510A>G
  • NM_000238.3:c.2510A>G
  • Q12809:p.Asp837Gly
Protein change:
D497G
Links:
UniProtKB: Q12809#VAR_068280; dbSNP: rs199473004
NCBI 1000 Genomes Browser:
rs199473004
Molecular consequence:
  • NM_000238.4:c.2510A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.1490A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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
SCV002745149Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Nov 22, 2023) 		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

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

Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome.

Khositseth A, Tester DJ, Will ML, Bell CM, Ackerman MJ.

Heart Rhythm. 2004 May;1(1):60-4.

PubMed [citation]
PMID:
15851119
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002745149.2

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

Description

The p.D837G variant (also known as c.2510A>G), located in coding exon 10 of the KCNH2 gene, results from an A to G substitution at nucleotide position 2510. The aspartic acid at codon 837 is replaced by glycine, an amino acid with similar properties, and is located in the cyclic nucleotide binding region of the protein. This variant has been reported in individuals with long QT syndrome (Khositseth A et al. Heart Rhythm. 2004;1(1):60-4; Ambry internal data). Immunoblot data suggest that this variant is a protein trafficking deficient alteration (Anderson CL et al. Nat Commun. 2014;5:5535). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Nov 24, 2024