NM_000218.3(KCNQ1):c.1032+1G>A AND Long QT syndrome

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 16, 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:: RCV000190169.6

Allele description

NM_000218.3(KCNQ1):c.1032+1G>A

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.1032+1G>A

HGVS:

NC_000011.10:g.2583546G>A
NG_008935.1:g.143556G>A
NM_000218.3:c.1032+1G>AMANE SELECT
NM_001406836.1:c.1032+1G>A
NM_001406837.1:c.762+1G>A
NM_001406838.1:c.588+1G>A
NM_181798.2:c.651+1G>A
LRG_287t1:c.1032+1G>A
LRG_287:g.143556G>A
NC_000011.9:g.2604776G>A
NM_000218.2:c.1032+1G>A

Links:

dbSNP: rs397508070

NCBI 1000 Genomes Browser:

rs397508070

Molecular consequence:

NM_000218.3:c.1032+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406836.1:c.1032+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406837.1:c.762+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406838.1:c.588+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181798.2:c.651+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222019	Medical Research Institute, Tokyo Medical and Dental University See additional submitters Division of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo	no assertion criteria provided	Likely pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]
SCV001576508	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 16, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16199547, 9323054, 19862833, 16244680, 19716085, 26132555, 34319147, 34505893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000222019

Medical Research Institute, Tokyo Medical and Dental University

See additional submitters

no assertion criteria provided

Likely pathogenic

germline

research

PubMed (1)
[See all records that cite this PMID]

SCV001576508

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 16, 2023)

germline

clinical testing

PubMed (9)
[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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 (9)

Details of each submission

From Medical Research Institute, Tokyo Medical and Dental University, SCV000222019.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

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

From Invitae, SCV001576508.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 7 of the KCNQ1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with long QT syndrome (PMID: 16244680, 19716085, 26132555, 34319147, 34505893). ClinVar contains an entry for this variant (Variation ID: 52937). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 23, 2024

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