NM_000218.3(KCNQ1):c.573_577del (p.Arg192fs) AND KCNQ1-related disorder

Germline classification:: Pathogenic (1 submission)
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:: RCV003335078.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.573_577del (p.Arg192fs)]

NM_000218.3(KCNQ1):c.573_577del (p.Arg192fs)

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.573_577del (p.Arg192fs)

Other names:

NP_000209.2:p.Arg518Ter

HGVS:

NC_000011.10:g.2570723_2570727del
NG_008935.1:g.130733_130737del
NM_000218.2:c.572_576del
NM_000218.3:c.573_577delMANE SELECT
NM_001406836.1:c.573_577delGCGCT
NM_001406837.1:c.303_307delGCGCT
NM_181798.2:c.192_196delGCGCT
NP_000209.2:p.Arg192Cysfs
NP_000209.2:p.Arg192fs
NP_000209.2:p.Arg192fs
NP_001393765.1:p.Arg192Cysfs
NP_001393766.1:p.Arg102Cysfs
NP_861463.1:p.Arg65Cysfs
NP_861463.1:p.Arg65fs
LRG_287t1:c.573_577del
LRG_287t2:c.192_196del
LRG_287:g.130733_130737del
LRG_287p1:p.Arg192fs
LRG_287p2:p.Arg65fs
NC_000011.9:g.2591950_2591954del
NC_000011.9:g.2591953_2591957del
NM_000218.2:c.572_576del
NM_000218.2:c.573_577del
NM_000218.2:c.573_577delGCGCT
NM_000218.3:c.573_577del
NM_181798.1:c.192_196del
NM_181798.1:c.192_196delGCGCT
NR_040711.2:n.466_470delGCGCT
p.Arg192CysfsX91
p.R192CfsX91

Protein change:

R192fs

Links:

dbSNP: rs397508118

NCBI 1000 Genomes Browser:

rs397508118

Molecular consequence:

NM_000218.3:c.573_577del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.573_577delGCGCT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.303_307delGCGCT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.192_196delGCGCT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: KCNQ1-related disorder
Synonyms:: KCNQ1-Related Disorders; KCNQ1-related condition
Identifiers:: MedGen: CN239322

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046104	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046104

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046104.1

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

Description

This frameshifting variant in exon 3 of 16 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a heterozygous change in multiple individuals with long QT syndrome (PMID: 10560595, 22539601, 24666684, 11530100, 23392653). Functional studies showed the c.573_577del (p.Arg192CysfsTer91) variant causes a dominant-negative effect on KCNQ1 function (PMID: 11530100). The c.573_577del (p.Arg192CysfsTer91) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (4/249462) and thus is presumed to be rare. Based on the available evidence, the c.573_577del (p.Arg192CysfsTer91) variant is classified as Pathogenic.

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

Last Updated: May 12, 2024

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