NM_000218.3(KCNQ1):c.781-19TG[2] AND not specified

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: May 24, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000150867.14

Allele description [Variation Report for NM_000218.3(KCNQ1):c.781-19TG[2]]

NM_000218.3(KCNQ1):c.781-19TG[2]

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.781-19TG[2]

HGVS:

NC_000011.10:g.2572828GT[2]
NC_000011.9:g.2594057_2594058del
NG_008935.1:g.132838GT[2]
NM_000218.3:c.781-19TG[2]MANE SELECT
NM_001406836.1:c.781-19TG[2]
NM_001406837.1:c.511-19TG[2]
NM_001406838.1:c.478-10608TG[2]
NM_181798.2:c.400-19TG[2]
LRG_287:g.132838GT[2]
NC_000011.9:g.2594057_2594058del
NC_000011.9:g.2594058GT[2]
NC_000011.9:g.2594062_2594063delGT
NM_000218.2:c.781-14_781-13delGT

Links:

dbSNP: rs727503103

NCBI 1000 Genomes Browser:

rs727503103

Molecular consequence:

NM_000218.3:c.781-19TG[2] - intron variant - [Sequence Ontology: SO:0001627]
NM_001406836.1:c.781-19TG[2] - intron variant - [Sequence Ontology: SO:0001627]
NM_001406837.1:c.511-19TG[2] - intron variant - [Sequence Ontology: SO:0001627]
NM_001406838.1:c.478-10608TG[2] - intron variant - [Sequence Ontology: SO:0001627]
NM_181798.2:c.400-19TG[2] - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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
SCV000198427	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Jan 3, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001737816	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (May 24, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000198427

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely benign
(Jan 3, 2014)

germline

clinical testing

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

SCV001737816

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(May 24, 2021)

germline

clinical testing

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
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000198427.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

781-14_781-13delGT in Intron 5 of KCNQ1: This variant is not expected to have cl inical significance because it is not located in the splice consensus sequence a nd computational tools do not predict an impact to splicing.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737816.1

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

Description

Variant summary: KCNQ1 c.781-14_781-13delGT alters a 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 9.1e-05 in 395002 control chromosomes, predominantly at a frequency of 0.00057 within the East Asian subpopulation in the gnomAD database (v2.1 exomes and v3.1 genomes datasets). The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 5.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNQ1 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.781-14_781-13delGT in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

#	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 26, 2024

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