NM_000238.3(KCNH2):c.2510A>G (p.Asp837Gly) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jul 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000469039.3

Allele description [Variation Report for NM_000238.3(KCNH2):c.2510A>G (p.Asp837Gly)]

NM_000238.3(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_000238.3(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_000238.3:c.2510A>G
  • NM_172057.2:c.1490A>G
  • NP_000229.1:p.Asp837Gly
  • NP_742054.1:p.Asp497Gly
  • LRG_288t1:c.2510A>G
  • LRG_288t3:c.1490A>G
  • LRG_288:g.33989A>G
  • LRG_288p1:p.Asp837Gly
  • LRG_288p3:p.Asp497Gly
  • NC_000007.13:g.150646026T>C
  • NM_000238.2:c.2510A>G
  • Q12809:p.Asp837Gly
Protein change:
D497G
Links:
UniProtKB: Q12809#VAR_068280; dbSNP: rs199473004
NCBI 1000 Genomes Browser:
rs199473004
Molecular consequence:
  • NM_000238.3:c.2510A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.2:c.1490A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976; OMIM: PS192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000543440Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 30, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.

Partemi S, Vidal MC, Striano P, Campuzano O, Allegue C, Pezzella M, Elia M, Parisi P, Belcastro V, Casellato S, Giordano L, Mastrangelo M, Pietrafusa N, Striano S, Zara F, Bianchi A, Buti D, La Neve A, Tassinari CA, Oliva A, Brugada R.

Int J Legal Med. 2015 May;129(3):495-504. doi: 10.1007/s00414-014-1063-4. Epub 2014 Aug 15.

PubMed [citation]
PMID:
25119684

Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome.

Migdalovich D, Moss AJ, Lopes CM, Costa J, Ouellet G, Barsheshet A, McNitt S, Polonsky S, Robinson JL, Zareba W, Ackerman MJ, Benhorin J, Kaufman ES, Platonov PG, Shimizu W, Towbin JA, Vincent GM, Wilde AA, Goldenberg I.

Heart Rhythm. 2011 Oct;8(10):1537-43. doi: 10.1016/j.hrthm.2011.03.049. Epub 2011 Mar 25.

PubMed [citation]
PMID:
21440677
PMCID:
PMC4028036
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000543440.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces aspartic acid with glycine at codon 837 of the KCNH2 protein (p.Asp837Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with long QT syndrome (PMID: 25119684, 21440677). ClinVar contains an entry for this variant (Variation ID: 67407). This variant has been reported to affect KCNH2 protein function (PMID: 25417810). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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