NM_000218.3(KCNQ1):c.683+5G>A AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 10, 2020
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:: RCV001255476.9

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)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001431894	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 10, 2020)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 19841300, 23631430, 22456477, 19862833, 26318259, 17470695, 26669661, 28438721, 29622001, 29740400, 27917693 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001431894

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 10, 2020)

germline

clinical testing

PubMed (11)
[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

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

Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.

Lieve KV, Williams L, Daly A, Richard G, Bale S, Macaya D, Chung WK.

Genet Test Mol Biomarkers. 2013 Jul;17(7):553-61. doi: 10.1089/gtmb.2012.0118. Epub 2013 Apr 30.

PubMed [citation]

PMID:: 23631430

See all PubMed Citations (11)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001431894.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

Variant summary: KCNQ1 c.683+5G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 248582 control chromosomes (gnomAD and publication data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.683+5G>A has been reported in the literature in individuals affected with LQTS and Jervell and Lange-Nielsen Syndrome (Moss_2007, Kapa_2009, Barsheshet_2012, Lieve_2013, Ruwald_2016, Wang_2016, Al-Hassnan_2017, Koponen_2018, Huttunen_2018). These reports do not provide unequivocal conclusions about association of the variant with Arrhythmia. In addition, co-occurrence with another pathogenic variant has been reported (KCNQ1 c.1484_1485delCT, p.L496AfsX19, Wang_2016), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Oct 20, 2024

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