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

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Oct 29, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000678812.14

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_000218.3:c.944A>GMANE SELECT
  • NM_001406836.1:c.944A>G
  • NM_001406837.1:c.674A>G
  • NM_001406838.1:c.500A>G
  • NM_181798.2:c.563A>G
  • NP_000209.2:p.Tyr315Cys
  • NP_000209.2:p.Tyr315Cys
  • NP_001393765.1:p.Tyr315Cys
  • NP_001393766.1:p.Tyr225Cys
  • NP_001393767.1:p.Tyr167Cys
  • NP_861463.1:p.Tyr188Cys
  • 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
  • NM_000218.2:c.944A>G
  • NM_181798.1:c.563A>G
  • NR_040711.2:n.837A>G
  • P51787:p.Tyr315Cys
Protein change:
Y167C
Links:
UniProtKB: P51787#VAR_008946; dbSNP: rs74462309
NCBI 1000 Genomes Browser:
rs74462309
Molecular consequence:
  • NM_000218.3:c.944A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.944A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.674A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.500A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.563A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000804998Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
no assertion criteria provided
Likely pathogenic
(Jan 18, 2017) 		germlineclinical testing

SCV001588720Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 29, 2023) 		germlineclinical testing

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

Help

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

Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1.

Splawski I, Shen J, Timothy KW, Vincent GM, Lehmann MH, Keating MT.

Genomics. 1998 Jul 1;51(1):86-97.

PubMed [citation]
PMID:
9693036

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001588720.4

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 315 of the KCNQ1 protein (p.Tyr315Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with long QT syndrome (PMID: 9693036, 12702160, 18774102, 21451124, 24217263, 24606995). ClinVar contains an entry for this variant (Variation ID: 53140). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ1 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 20, 2024