NM_000218.3(KCNQ1):c.421G>A (p.Val141Met) AND Cardiovascular phenotype

Clinical significance:Pathogenic (Last evaluated: Dec 2, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000621525.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.421G>A (p.Val141Met)]

NM_000218.3(KCNQ1):c.421G>A (p.Val141Met)

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.421G>A (p.Val141Met)
HGVS:
  • NC_000011.10:g.2527962G>A
  • NG_008935.1:g.87972G>A
  • NM_000218.2:c.421G>A
  • NM_000218.3:c.421G>AMANE SELECT
  • NM_181798.1:c.40G>A
  • NP_000209.2:p.Val141Met
  • NP_000209.2:p.Val141Met
  • NP_861463.1:p.Val14Met
  • LRG_287t1:c.421G>A
  • LRG_287t2:c.40G>A
  • LRG_287:g.87972G>A
  • LRG_287p1:p.Val141Met
  • LRG_287p2:p.Val14Met
  • NC_000011.9:g.2549192G>A
Protein change:
V141M; VAL141MET
Links:
OMIM: 607542.0045; dbSNP: rs199472687
NCBI 1000 Genomes Browser:
rs199472687
Molecular consequence:
  • NM_000218.2:c.421G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.421G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.40G>A - 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
SCV000737832Ambry Geneticscriteria provided, single submitter
Pathogenic
(Dec 2, 2016)
germlineclinical testing

PubMed (5)
[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

De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero.

Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E, Santos-de-Soto J, Grueso-Montero J, Diaz-Enfante E, Brugada P, Sachse F, Sanguinetti MC, Brugada R.

Cardiovasc Res. 2005 Dec 1;68(3):433-40. Epub 2005 Aug 18.

PubMed [citation]
PMID:
16109388

Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels.

Restier L, Cheng L, Sanguinetti MC.

J Physiol. 2008 Sep 1;586(17):4179-91. doi: 10.1113/jphysiol.2008.157511. Epub 2008 Jul 3.

PubMed [citation]
PMID:
18599533
PMCID:
PMC2652179
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000737832.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The p.V141M pathogenic mutation (also known as c.421G>A), located in coding exon 2 of the KCNQ1 gene, results from a G to A substitution at nucleotide position 421. The valine at codon 141 is replaced by methionine, an amino acid with highly similar properties. This mutation was reported in individuals with very early age onset atrial fibrillation (AF) and short QT syndrome (SQTS), including several reported de novo cases (Hong K et al. Cardiovasc. Res., 2005 Dec;68:433-40; Villafañe J et al. J. Am. Coll. Cardiol., 2013 Mar;61:1183-91; Harrell DT et al. Int. J. Cardiol., 2015 Apr;190:393-402; Sarquella-Brugada G et al. Heart Rhyth. Case Rpt, 2015 Jul;1:193-197). Functional studies demonstrated that this is a gain-of-function mutation resulting in slowed deactivation of the potassium channel (Hong K et al. Cardiovasc. Res., 2005 Dec;68:433-40; Restier L et al. J. Physiol. (Lond.), 2008 Sep;586:4179-91; Chan PJ et al. J. Gen. Physiol., 2012 Feb;139:135-44). 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 25, 2021

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