NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys) AND Long QT syndrome 1

Clinical significance:Pathogenic (Last evaluated: Feb 1, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000587627.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)]

NM_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)

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_000218.3(KCNQ1):c.520C>T (p.Arg174Cys)
Other names:
p.R174C:CGC>TGC
HGVS:
  • NC_000011.10:g.2570670C>T
  • NG_008935.1:g.130680C>T
  • NM_000218.2:c.520C>T
  • NM_000218.3:c.520C>TMANE SELECT
  • NM_181798.1:c.139C>T
  • NP_000209.2:p.Arg174Cys
  • NP_000209.2:p.Arg174Cys
  • NP_861463.1:p.Arg47Cys
  • LRG_287t1:c.520C>T
  • LRG_287t2:c.139C>T
  • LRG_287:g.130680C>T
  • LRG_287p1:p.Arg174Cys
  • LRG_287p2:p.Arg47Cys
  • NC_000011.9:g.2591900C>T
  • P51787:p.Arg174Cys
Protein change:
R174C
Links:
UniProtKB: P51787#VAR_001517; dbSNP: rs199472696
NCBI 1000 Genomes Browser:
rs199472696
Molecular consequence:
  • NM_000218.2:c.520C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.520C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.139C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 1 (LQT1)
Identifiers:
MONDO: MONDO:0100316; MedGen: C4551647; Orphanet: 101016; Orphanet: 768; OMIM: 192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000695990Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Feb 1, 2016)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]
PMID:
15840476
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695990.1

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

Description

Variant summary: The c.520C>T (p.R174C) in KCNQ1 gene is a missense variant that involves a conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant is present in the control population dataset of ExAC at a low frequency (0.0008%) which does not exceed the maximum allele frequency for a pathogenic KCNQ1 variant (0.01%). This variant has been reported in the literature in multiple affected individuals presented with elongated QTc interval, including one homozygous pt with severe arrhythmic presentation. Other alterations of the same codon, p.R174H, p.R174L and p.R174P have been reported in pts with LQTS. Functional studies showed p.R174C alters the normal channel activity. In addition, several reputable databases/clinical laboratories classified the variant as Pathogenic. Therefore, this variant was classified as Pathogenic.

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

Last Updated: Nov 20, 2021

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