NM_000218.3(KCNQ1):c.683+5G>A AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 8, 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:: RCV002362678.10

Allele description [Variation Report for NM_000218.3(KCNQ1):c.683+5G>A]

NM_000218.3(KCNQ1):c.683+5G>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.683+5G>A

HGVS:

NC_000011.10:g.2571408G>A
NG_008935.1:g.131418G>A
NM_000218.3:c.683+5G>AMANE SELECT
NM_001406836.1:c.683+5G>A
NM_001406837.1:c.413+5G>A
NM_001406838.1:c.478-12027G>A
NM_181798.2:c.302+5G>A
LRG_287t1:c.683+5G>A
LRG_287:g.131418G>A
NC_000011.9:g.2592638G>A
NM_000218.2:c.683+5G>A

Links:

dbSNP: rs397508122

NCBI 1000 Genomes Browser:

rs397508122

Molecular consequence:

NM_000218.3:c.683+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406836.1:c.683+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406837.1:c.413+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001406838.1:c.478-12027G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_181798.2:c.302+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002664970	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 8, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17470695, 19841300, 23631430, 25525159, 27917693, 28438721 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002664970

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 8, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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

Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.

Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S.

Circulation. 2007 May 15;115(19):2481-9. Epub 2007 Apr 30.

PubMed [citation]

PMID:: 17470695
PMCID:: PMC3332528

Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ.

Circulation. 2009 Nov 3;120(18):1752-60. doi: 10.1161/CIRCULATIONAHA.109.863076. Epub 2009 Oct 19.

PubMed [citation]

PMID:: 19841300
PMCID:: PMC3025752

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002664970.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.683+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 4 in the KCNQ1 gene. This alteration has been detected in individuals with long QT syndrome (LQTS) and in compound heterozygotes with Jervell and Lange-Nielsen syndrome (JLNS), as well as in some asymptomatic carrier parents (Moss AJ et al. Circulation, 2007 May;115:2481-9; Kapa S et al. Circulation, 2009 Nov;120:1752-60; Crehalet H et al. Cardiogen., 2012;2:26-31; Lieve KV et al. Genet Test Mol Biomarkers, 2013 Jul;17:553-61; Wang C et al. Acta Otolaryngol., 2017 May;137:522-528; Al-Hassnan ZN et al. Heart Rhythm, 2017 Aug;14:1191-1199). RNA splicing studies demonstrated this alteration leads to skipping of exon 4 (Crehalet H et al. Cardiogen., 2012;2:26-31). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the majority of available evidence to date, this variant is likely to be 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: Nov 10, 2024

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