U.S. flag

An official website of the United States government

NM_000218.3(KCNQ1):c.1046C>A (p.Ser349Ter) AND Long QT syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 3, 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:
RCV000472268.7

Allele description

NM_000218.3(KCNQ1):c.1046C>A (p.Ser349Ter)

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.1046C>A (p.Ser349Ter)
HGVS:
  • NC_000011.10:g.2585225C>A
  • NG_008935.1:g.145235C>A
  • NM_000218.3:c.1046C>AMANE SELECT
  • NM_001406837.1:c.776C>A
  • NM_181798.2:c.665C>A
  • NP_000209.2:p.Ser349Ter
  • NP_000209.2:p.Ser349Ter
  • NP_001393766.1:p.Ser259Ter
  • NP_861463.1:p.Ser222Ter
  • NP_861463.1:p.Ser222Ter
  • LRG_287t1:c.1046C>A
  • LRG_287t2:c.665C>A
  • LRG_287:g.145235C>A
  • LRG_287p1:p.Ser349Ter
  • LRG_287p2:p.Ser222Ter
  • NC_000011.9:g.2606455C>A
  • NM_000218.2:c.1046C>A
  • NM_181798.1:c.665C>A
  • NR_040711.2:n.939C>A
Protein change:
S222*
Links:
dbSNP: rs199472765
NCBI 1000 Genomes Browser:
rs199472765
Molecular consequence:
  • NM_000218.3:c.1046C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406837.1:c.776C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181798.2:c.665C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000543309Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 3, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

T wave morphology analysis distinguishes between KvLQT1 and HERG mutations in long QT syndrome.

Kanters JK, Fanoe S, Larsen LA, Bloch Thomsen PE, Toft E, Christiansen M.

Heart Rhythm. 2004 Sep;1(3):285-92.

PubMed [citation]
PMID:
15851171

Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.

Shalaby FY, Levesque PC, Yang WP, Little WA, Conder ML, Jenkins-West T, Blanar MA.

Circulation. 1997 Sep 16;96(6):1733-6.

PubMed [citation]
PMID:
9323054
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000543309.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 405261). This premature translational stop signal has been observed in individual(s) with long QT Syndrome (PMID: 15851171). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser349*) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833).

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

Last Updated: Feb 28, 2024