NM_000238.3(KCNH2):c.1408A>G (p.Asn470Asp) AND Long QT syndrome 2

Clinical significance:Pathogenic (Last evaluated: Feb 17, 2006)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000015502.25

Allele description [Variation Report for NM_000238.3(KCNH2):c.1408A>G (p.Asn470Asp)]

NM_000238.3(KCNH2):c.1408A>G (p.Asn470Asp)

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.1408A>G (p.Asn470Asp)
HGVS:
  • NC_000007.14:g.150952574T>C
  • NG_008916.1:g.30353A>G
  • NM_000238.3:c.1408A>G
  • NM_172056.2:c.1408A>G
  • NM_172057.2:c.388A>G
  • NP_000229.1:p.Asn470Asp
  • NP_742053.1:p.Asn470Asp
  • NP_742054.1:p.Asn130Asp
  • LRG_288t1:c.1408A>G
  • LRG_288t2:c.1408A>G
  • LRG_288t3:c.388A>G
  • LRG_288:g.30353A>G
  • LRG_288p1:p.Asn470Asp
  • LRG_288p2:p.Asn470Asp
  • LRG_288p3:p.Asn130Asp
  • NC_000007.13:g.150649662T>C
Protein change:
N130D; ASN470ASP
Links:
OMIM: 152427.0002; dbSNP: 121912505
NCBI 1000 Genomes Browser:
rs121912505
Molecular consequence:
  • NM_000238.3:c.1408A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 2 (LQT2)
Synonyms:
LONG QT SYNDROME 2, ACQUIRED, REDUCED SUSCEPTIBILITY TO
Identifiers:
MedGen: C3150943; Orphanet: 101016; Orphanet: 768; OMIM: 613688
Prevalence:
1-5 / 10 000 101016768

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000035767OMIMno assertion criteria providedPathogenic
(Feb 17, 2006)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.

Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT.

Cell. 1995 Mar 10;80(5):795-803.

PubMed [citation]
PMID:
7889573

Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome.

Gong Q, Jones MA, Zhou Z.

J Biol Chem. 2006 Feb 17;281(7):4069-74. Epub 2005 Dec 16.

PubMed [citation]
PMID:
16361248
PMCID:
PMC1624912

Details of each submission

From OMIM, SCV000035767.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In an LQT2 (613688) kindred, Curran et al. (1995) found that an aberrant SSCP conformer was due to an A-to-G substitution at position 1408, a mutation that resulted in substitution of aspartic acid for a conserved asparagine in the second transmembrane domain (N470D).

Gong et al. (2006) showed that both wildtype and mutant KCNH2 with the N470D substitution associated with the endoplasmic reticulum chaperone protein calnexin (CANX; 114217). However, the mutant protein showed prolonged association with calnexin, and like immature wildtype KCNH2, was more sensitive than mature wildtype KCNH2 to trypsin digestion. Gong et al. (2006) concluded that aberrant protein folding increases the association of mutant KCNH2 with calnexin and results in defective protein trafficking.

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

Last Updated: Jul 27, 2016