NM_181798.1(KCNQ1):c.49A>G (p.Thr17Ala) AND Cardiovascular phenotype

Clinical significance:Uncertain significance (Last evaluated: Jun 27, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000618499.1

Allele description [Variation Report for NM_181798.1(KCNQ1):c.49A>G (p.Thr17Ala)]

NM_181798.1(KCNQ1):c.49A>G (p.Thr17Ala)

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.49A>G (p.Thr17Ala)
HGVS:
  • NC_000011.10:g.2527971A>G
  • NG_008935.1:g.87981A>G
  • NM_000218.2:c.430A>G
  • NM_181798.1:c.49A>G
  • NP_000209.2:p.Thr144Ala
  • NP_861463.1:p.Thr17Ala
  • LRG_287t1:c.430A>G
  • LRG_287t2:c.49A>G
  • LRG_287:g.87981A>G
  • LRG_287p1:p.Thr144Ala
  • LRG_287p2:p.Thr17Ala
  • NC_000011.9:g.2549201A>G
  • P51787:p.Thr144Ala
Protein change:
T144A
Links:
UniProtKB: P51787#VAR_074936; dbSNP: rs199473451
NCBI 1000 Genomes Browser:
rs199473451
Molecular consequence:
  • NM_000218.2:c.430A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.49A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000738071Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Jun 27, 2017)
germlineclinical testing

PubMed (4)
[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

Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome.

Zareba W, Moss AJ, Sheu G, Kaufman ES, Priori S, Vincent GM, Towbin JA, Benhorin J, Schwartz PJ, Napolitano C, Hall WJ, Keating MT, Qi M, Robinson J, Andrews ML; International LQTS Registry, University of Rochester, Rochester, New York..

J Cardiovasc Electrophysiol. 2003 Nov;14(11):1149-53.

PubMed [citation]
PMID:
14678125

Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of cardiovascular diseases.

Miller TE, You L, Myerburg RJ, Benke PJ, Bishopric NH.

Genet Med. 2007 Jan;9(1):23-33. Erratum in: Genet Med. 2007 Feb;9(2):135.

PubMed [citation]
PMID:
17224687
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000738071.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The p.T144A variant (also known as c.430A>G), located in coding exon 2 of the KCNQ1 gene, results from an A to G substitution at nucleotide position 430. The threonine at codon 144 is replaced by alanine, an amino acid with similar properties, and is located in the S1-S2 domain. This variant has been associated with long QT syndrome (LQTS) in a few individuals, but clinical details were limited and at least one of the individuals harbored another KCNQ1 alteration (p.R594P) in cis (Zareba W et al. J. Cardiovasc. Electrophysiol. 2003;14:1149-53; Miller TE et al. Genet. Med. 2007;9:23-33; Kapplinger JD et al. Heart Rhythm. 2009;6:1297-303). The equivalent alterations in KCNQ1 paralogs KCNQ2 (p.T114A) and KCNQ3 (p.T144A) lead to deficient protein function in vitro; however, no similar studies have been performed for this alteration (Füll Y et al. Pflugers Arch. 2013;465:797-804). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 8, 2021

Support Center