NM_000238.4(KCNH2):c.2694_2699dup (p.Asp898_Thr899dup) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Sep 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000699419.4

Allele description [Variation Report for NM_000238.4(KCNH2):c.2694_2699dup (p.Asp898_Thr899dup)]

NM_000238.4(KCNH2):c.2694_2699dup (p.Asp898_Thr899dup)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.2694_2699dup (p.Asp898_Thr899dup)
HGVS:
  • NC_000007.14:g.150948445_150948446insGTGTCC
  • NG_008916.1:g.34483_34484insACACGG
  • NM_000238.4:c.2694_2699dupMANE SELECT
  • NM_172057.3:c.1674_1679dup
  • NP_000229.1:p.Asp898_Thr899dup
  • NP_742054.1:p.Asp558_Thr559dup
  • LRG_288:g.34483_34484insACACGG
  • NC_000007.13:g.150645531_150645532insCCGTGT
  • NC_000007.13:g.150645533_150645534insGTGTCC
  • NM_000238.3:c.2692_2692+1insACACGG
Links:
dbSNP: rs1399804251
NCBI 1000 Genomes Browser:
rs1399804251
Molecular consequence:
  • NM_000238.4:c.2694_2699dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_172057.3:c.1674_1679dup - inframe_insertion - [Sequence Ontology: SO:0001821]

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
SCV000828128Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 24, 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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]
PMID:
10973849
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000828128.4

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

Description

This sequence change affects donor splice site in intron 11 of the KCNH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 576827). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 10973849, 19862833). 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 25, 2021

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