NM_000218.3(KCNQ1):c.944A>G (p.Tyr315Cys) AND Long QT syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000678812.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.944A>G (p.Tyr315Cys)]

NM_000218.3(KCNQ1):c.944A>G (p.Tyr315Cys)

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.944A>G (p.Tyr315Cys)
Other names:
p.Y315C:TAT>TGT
HGVS:
  • NC_000011.10:g.2583457A>G
  • NG_008935.1:g.143467A>G
  • NM_000218.2:c.944A>G
  • NM_000218.3:c.944A>GMANE SELECT
  • NM_181798.1:c.563A>G
  • NP_000209.2:p.Tyr315Cys
  • NP_000209.2:p.Tyr315Cys
  • NP_861463.1:p.Tyr188Cys
  • LRG_287t1:c.944A>G
  • LRG_287t2:c.563A>G
  • LRG_287:g.143467A>G
  • LRG_287p1:p.Tyr315Cys
  • LRG_287p2:p.Tyr188Cys
  • NC_000011.9:g.2604687A>G
  • P51787:p.Tyr315Cys
Protein change:
Y188C
Links:
UniProtKB: P51787#VAR_008946; dbSNP: rs74462309
NCBI 1000 Genomes Browser:
rs74462309
Molecular consequence:
  • NM_000218.2:c.944A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000218.3:c.944A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.1:c.563A>G - 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
SCV000804998Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospitalno assertion criteria providedLikely pathogenic
(Jan 18, 2017)
germlineclinical testing

SCV001588720Invitaecriteria provided, single submitter
Pathogenic
(Aug 14, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Long QT syndrome in South Africa: the results of comprehensive genetic screening.

Hedley PL, Durrheim GA, Hendricks F, Goosen A, Jespersgaard C, Støvring B, Pham TT, Christiansen M, Brink PA, Corfield VA.

Cardiovasc J Afr. 2013 Jul;24(6):231-7. doi: 10.5830/CVJA-2013-032.

PubMed [citation]
PMID:
24217263
PMCID:
PMC3772322

KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death.

Chen S, Zhang L, Bryant RM, Vincent GM, Flippin M, Lee JC, Brown E, Zimmerman F, Rozich R, Szafranski P, Oberti C, Sterba R, Marangi D, Tchou PJ, Chung MK, Wang Q.

Clin Genet. 2003 Apr;63(4):273-82.

PubMed [citation]
PMID:
12702160
PMCID:
PMC1579805
See all PubMed Citations (8)

Details of each submission

From Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital, SCV000804998.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001588720.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces tyrosine with cysteine at codon 315 of the KCNQ1 protein (p.Tyr315Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with long QT syndrome (PMID: 24217263, 12702160, 18774102, 21451124, 9693036, 24606995). ClinVar contains an entry for this variant (Variation ID: 53140). This variant has been reported to affect KCNQ1 protein function (PMID: 11087258, 21451124). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 30, 2021

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