NM_181798.1(KCNQ1):c.584C>T (p.Thr195Met) AND Cardiovascular phenotype

Clinical significance:Pathogenic (Last evaluated: Aug 16, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000247480.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.584C>T (p.Thr195Met)]

NM_181798.1(KCNQ1):c.584C>T (p.Thr195Met)

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.584C>T (p.Thr195Met)
Other names:
p.T322M:ACG>ATG
HGVS:
  • NC_000011.10:g.2583478C>T
  • NG_008935.1:g.143488C>T
  • NM_000218.2:c.965C>T
  • NM_181798.1:c.584C>T
  • NP_000209.2:p.Thr322Met
  • NP_861463.1:p.Thr195Met
  • LRG_287t1:c.965C>T
  • LRG_287t2:c.584C>T
  • LRG_287:g.143488C>T
  • LRG_287p1:p.Thr322Met
  • LRG_287p2:p.Thr195Met
  • NC_000011.9:g.2604708C>T
  • P51787:p.Thr322Met
Protein change:
T195M
Links:
UniProtKB: P51787#VAR_074692; dbSNP: rs199472755
NCBI 1000 Genomes Browser:
rs199472755
Molecular consequence:
  • NM_000218.2:c.965C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.584C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000320507Ambry Geneticscriteria provided, single submitter
Pathogenic
(Aug 16, 2018)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.

Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S.

Circulation. 2007 May 15;115(19):2481-9. Epub 2007 Apr 30.

PubMed [citation]
PMID:
17470695
PMCID:
PMC3332528
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000320507.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (11)

Description

The p.T322M pathogenic mutation (also known as c.965C>T), located in coding exon 7 of the KCNQ1 gene, results from a C to T substitution at nucleotide position 965. The threonine at codon 322 is replaced by methionine, an amino acid with some similar properties, and is located in the pore/S6 transmembrane spanning region. This alteration has been reported in multiple unrelated individuals with known or suspected long QT syndrome (LQTS) (Napolitano C et al. JAMA. 2005;294(23):2975-80; Moss AJ et al. Circulation. 2007;115(19):2481-9; Kapplinger JD et al. Heart Rhythm. 2009;6(9):1297-303; Aziz PF et al. Circ Arrhythm Electrophysiol. 2011;4(6):867-73; Clur SB et al. Circ Arrhythm Electrophysiol. 2018;11(4):e005797). One study reported this alteration in multiple individuals in several families with LQTS (Burgess DE et al. Biochemistry. 2012;51(45):9076-85). This alteration has been reported in the homozygous state in two siblings with Jervell and Lange-Nielsen syndrome, and in the heterozygous state in two relatives reported to have prolonged QT intervals (Zhang S et al. BMC Med Genet. 2008;9:24). This alteration was also reported to co-occur with a KCNQ1 frame shift alteration in a patient with LQTS and syncope starting at three years of age (Toyota N et al. Heart Vessels. 2015 Sep; 30(5):687-91). In addition, in vitro studies suggest this alteration to result in abnormal protein function and trafficking (Burgess DE et al. Biochemistry. 2012;51(45):9076-85; Mousavi Nik A et al. Front Cell Neurosci. 2015;9:32). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 8, 2021

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