NM_181798.1(KCNQ1):c.545C>T (p.Thr182Ile) AND Long QT syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jul 29, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001379437.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.545C>T (p.Thr182Ile)]

NM_181798.1(KCNQ1):c.545C>T (p.Thr182Ile)

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.545C>T (p.Thr182Ile)
HGVS:
  • NC_000011.10:g.2583439C>T
  • NG_008935.1:g.143449C>T
  • NM_000218.2:c.926C>T
  • NM_181798.1:c.545C>T
  • NP_000209.2:p.Thr309Ile
  • NP_861463.1:p.Thr182Ile
  • LRG_287t1:c.926C>T
  • LRG_287t2:c.545C>T
  • LRG_287:g.143449C>T
  • LRG_287p1:p.Thr309Ile
  • LRG_287p2:p.Thr182Ile
  • NC_000011.9:g.2604669C>T
Protein change:
T182I
Links:
dbSNP: rs199472743
NCBI 1000 Genomes Browser:
rs199472743
Molecular consequence:
  • NM_000218.2:c.926C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.545C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001577240Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 29, 2020)
germlineclinical testing

PubMed (6)
[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

Linkage and mutation analysis in two Taiwanese families with long QT syndrome.

Ko YL, Tai DY, Chen SA, Lee-Chen GJ, Chu CH, Lin MW.

J Formos Med Assoc. 2001 Nov;100(11):767-71.

PubMed [citation]
PMID:
11802537

Mutation Analysis of KCNQ1, KCNH2 and SCN5A Genes in Taiwanese Long QT Syndrome Patients.

Chang YS, Yang YW, Lin YN, Lin KH, Chang KC, Chang JG.

Int Heart J. 2015;56(4):450-3. doi: 10.1536/ihj.14-428. Epub 2015 Jun 26.

PubMed [citation]
PMID:
26118593
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001577240.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces threonine with isoleucine at codon 309 of the KCNQ1 protein (p.Thr309Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Long QT syndrome (PMID: 11802537, 26118593, 9482580). ClinVar contains an entry for this variant (Variation ID: 53132). This variant identified in the KCNQ1 gene is located in the pore region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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