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

This record was updated by the submitter. Please see the current version.

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

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mediator of RNA polymerase II transcription subunit 20 isoform 2 [Rattus norvegi...
mediator of RNA polymerase II transcription subunit 20 isoform 2 [Rattus norvegicus]
gi|475807388|ref|NP_001264296.1|

Protein
SRX1613605 (1)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000543309	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15851171, 9323054, 19862833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000543309

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 3, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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