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NM_000238.4(KCNH2):c.2681G>A (p.Arg894His) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 5, 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:
RCV001841406.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.2681G>A (p.Arg894His)]

NM_000238.4(KCNH2):c.2681G>A (p.Arg894His)

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.2681G>A (p.Arg894His)
HGVS:
  • NC_000007.14:g.150948455C>T
  • NG_008916.1:g.34472G>A
  • NM_000238.4:c.2681G>AMANE SELECT
  • NM_172057.3:c.1661G>A
  • NP_000229.1:p.Arg894His
  • NP_000229.1:p.Arg894His
  • NP_742054.1:p.Arg554His
  • LRG_288t1:c.2681G>A
  • LRG_288:g.34472G>A
  • LRG_288p1:p.Arg894His
  • NC_000007.13:g.150645543C>T
  • NM_000238.3:c.2681G>A
Protein change:
R554H
Links:
dbSNP: rs199473668
NCBI 1000 Genomes Browser:
rs199473668
Molecular consequence:
  • NM_000238.4:c.2681G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.1661G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001341531Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 5, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Atrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation.

Doñate Puertas R, Millat G, Ernens I, Gache V, Chauveau S, Morel E, Christin E, Couturier N, Devaux Y, Chevalier P.

Biomed Res Int. 2018;2018:4862480. doi: 10.1155/2018/4862480.

PubMed [citation]
PMID:
30276209
PMCID:
PMC6151856

Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing.

Li X, Liu N, Bai R.

Ann Hum Genet. 2020 Mar;84(2):161-168. doi: 10.1111/ahg.12359. Epub 2019 Nov 7.

PubMed [citation]
PMID:
31696929
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001341531.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with histidine at codon 894 of the KCNH2 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with atrial fibrillation and in an individual suspected to be affected with epilepsy (PMID: 30276209, 31696929). This variant has been identified in 25/275238 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The elevated variant allele frequency in the general population indicates that this variant may not be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 3, 2024