NM_000218.3(KCNQ1):c.585del (p.Lys196fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 17, 2018
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:: RCV002354240.9

Allele description [Variation Report for NM_000218.3(KCNQ1):c.585del (p.Lys196fs)]

NM_000218.3(KCNQ1):c.585del (p.Lys196fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.585del (p.Lys196fs)

Other names:

p.Lys196Serfs*41

HGVS:

NC_000011.10:g.2570735del
NC_000011.9:g.2591964delG
NG_008935.1:g.130745del
NM_000218.3:c.585delMANE SELECT
NM_001406836.1:c.585delG
NM_001406837.1:c.315delG
NM_181798.2:c.204delG
NP_000209.2:p.Lys196Serfs
NP_000209.2:p.Lys196fs
NP_000209.2:p.Lys196fs
NP_001393765.1:p.Lys196Serfs
NP_001393766.1:p.Lys106Serfs
NP_861463.1:p.Lys69Serfs
NP_861463.1:p.Lys69fs
LRG_287t1:c.585del
LRG_287t2:c.204del
LRG_287:g.130745del
LRG_287p1:p.Lys196fs
LRG_287p2:p.Lys69fs
NC_000011.9:g.2591964del
NC_000011.9:g.2591964delG
NC_000011.9:g.2591965del
NC_000011.9:g.2591965delG
NM_000218.2:c.584delG
NM_000218.2:c.585del
NM_000218.2:c.585delG
NM_181798.1:c.204del
NR_040711.2:n.478delG
p.K196SfsX41
p.Lys196SerfsX41

Protein change:

K196fs

Links:

dbSNP: rs397508120

NCBI 1000 Genomes Browser:

rs397508120

Molecular consequence:

NM_000218.3:c.585del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.585delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.315delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.204delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Rattus norvegicus RAS protein activator like 3 (Rasal3), transcript variant 2, mRNA
gi|2414128258|ref|NM_001134562.3|

Nucleotide
adhesion molecule, interacts with CXADR antigen 1 [Homo sapiens]
adhesion molecule, interacts with CXADR antigen 1 [Homo sapiens]
gi|23397451|ref|NP_694938.1|

Protein
Mus musculus tripartite motif-containing 60 (Trim60), mRNA
Mus musculus tripartite motif-containing 60 (Trim60), mRNA
gi|288541340|ref|NM_153097.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002647670	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 17, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12051962, 19716085 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002647670

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 17, 2018)

germline

clinical testing

PubMed (2)
[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

Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome.

Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T, Bowles NE, Towbin JA.

Mol Genet Metab. 2002 Apr;75(4):308-16.

PubMed [citation]

PMID:: 12051962

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

Details of each submission

From Ambry Genetics, SCV002647670.2

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

Description

The c.585delG pathogenic mutation, located in coding exon 3 of the KCNQ1 gene, results from a deletion of one nucleotide at nucleotide position 585, causing a translational frameshift with a predicted alternate stop codon (p.K196Sfs*41). This mutation was reported in an individual with Jervell and Lange-Nielsen syndrome, who had an additional KCNQ1 variant (Wang Z et al. Mol. Genet. Metab., 2002 Apr;75:308-16). Furthermore, in a study of long QT syndrome clinical genetic testing, this alteration was reported in four patients; however, clinical details were limited (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 13, 2024

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