NM_181798.1(KCNQ1):c.1399C>T (p.Arg467Ter) AND Long QT syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 11, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000815960.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.1399C>T (p.Arg467Ter)]

NM_181798.1(KCNQ1):c.1399C>T (p.Arg467Ter)

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.1399C>T (p.Arg467Ter)
Other names:
p.R594*:CGA>TGA
HGVS:
  • NC_000011.10:g.2778023C>T
  • NG_008935.1:g.338033C>T
  • NM_000218.2:c.1780C>T
  • NM_181798.1:c.1399C>T
  • NP_000209.2:p.Arg594Ter
  • NP_861463.1:p.Arg467Ter
  • LRG_287t1:c.1780C>T
  • LRG_287t2:c.1399C>T
  • LRG_287:g.338033C>T
  • LRG_287p1:p.Arg594Ter
  • LRG_287p2:p.Arg467Ter
  • NC_000011.9:g.2799253C>T
Protein change:
R467*
Links:
dbSNP: rs794728537
NCBI 1000 Genomes Browser:
rs794728537
Molecular consequence:
  • NM_000218.2:c.1780C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181798.1:c.1399C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000956441Invitaecriteria provided, single submitter
Pathogenic
(Sep 11, 2018)
germlineclinical testing

PubMed (7)
[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

The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward syndrome.

Novotny T, Kadlecova J, Janousek J, Gaillyova R, Bittnerova A, Florianova A, Sisakova M, Toman O, Chroust K, Papousek I, Spinar J.

Pacing Clin Electrophysiol. 2006 Sep;29(9):1013-5.

PubMed [citation]
PMID:
16981927

Large deletion in KCNQ1 identified in a family with Jervell and Lange-Nielsen syndrome.

Sung JY, Bae EJ, Park S, Kim SY, Hyun YJ, Park SS, Seong MW.

Ann Lab Med. 2014 Sep;34(5):395-8. doi: 10.3343/alm.2014.34.5.395. Epub 2014 Aug 21.

PubMed [citation]
PMID:
25187895
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000956441.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change results in a premature translational stop signal in the KCNQ1 gene (p.Arg594*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the KCNQ1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual referred for long QT syndrome testing (PMID: 23098067). ClinVar contains an entry for this variant (Variation ID: 200858). This variant disrupts the C-terminus of the KCNQ1 protein. Other variant(s) that disrupt this region (p.Arg632Glnfs*20) have been determined to be pathogenic (PMID: 10024302, 23098067, 23631430, 25187895, 19825999, 16981927). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 6, 2021

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