NM_181798.1(KCNQ1):c.302+1G>A AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Aug 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_181798.1(KCNQ1):c.302+1G>A]


KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000011.10:g.2571404G>A
  • NG_008935.1:g.131414G>A
  • NM_000218.2:c.683+1G>A
  • NM_181798.1:c.302+1G>A
  • LRG_287t1:c.683+1G>A
  • LRG_287t2:c.302+1G>A
  • LRG_287:g.131414G>A
  • NC_000011.9:g.2592634G>A
dbSNP: rs1589957233
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000218.2:c.683+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_181798.1:c.302+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]


Long QT syndrome (LQTS)
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)
SCV000946845Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 20, 2018)
germlineclinical testing

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

Summary from all submissions

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



Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.

Shalaby FY, Levesque PC, Yang WP, Little WA, Conder ML, Jenkins-West T, Blanar MA.

Circulation. 1997 Sep 16;96(6):1733-6.

PubMed [citation]

The genetic basis of long QT and short QT syndromes: a mutation update.

Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M.

Hum Mutat. 2009 Nov;30(11):1486-511. doi: 10.1002/humu.21106. Review.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000946845.1

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


This sequence change affects a donor splice site in intron 4 of the KCNQ1 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). Disruption of this splice site has been observed in an individual affected with long QT syndrome (PMID: 26132555). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 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.

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

Last Updated: Aug 26, 2021

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