NM_181798.1(KCNQ1):c.540+1G>T AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Sep 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:
RCV001377884.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.540+1G>T]

NM_181798.1(KCNQ1):c.540+1G>T

Gene:
KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.5
Genomic location:
Preferred name:
NM_181798.1(KCNQ1):c.540+1G>T
HGVS:
  • NC_000011.10:g.2572987G>T
  • NG_008935.1:g.132997G>T
  • NM_000218.2:c.921+1G>T
  • NM_181798.1:c.540+1G>T
  • LRG_287t1:c.921+1G>T
  • LRG_287t2:c.540+1G>T
  • LRG_287:g.132997G>T
  • NC_000011.9:g.2594217G>T
Links:
dbSNP: rs397508130
NCBI 1000 Genomes Browser:
rs397508130
Molecular consequence:
  • NM_000218.2:c.921+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_181798.1:c.540+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001575331Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 30, 2020)
germlineclinical testing

PubMed (5)
[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

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

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001575331.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects a donor splice site in intron 6 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). This variant has been observed in individual(s) with clinical features of long QT syndrome (PMID: 10973849) and Jervell and Lange-Nielsen syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 53126). 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.

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

Last Updated: Oct 7, 2021

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