NM_000218.3(KCNQ1):c.488del (p.Leu163fs) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 2, 2015
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:: RCV000217623.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.488del (p.Leu163fs)]

NM_000218.3(KCNQ1):c.488del (p.Leu163fs)

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.488del (p.Leu163fs)

HGVS:

NC_000011.10:g.2570638del
NG_008935.1:g.130648del
NM_000218.3:c.488delMANE SELECT
NM_001406836.1:c.488delT
NM_001406837.1:c.218delT
NM_181798.2:c.107delT
NP_000209.2:p.Leu163Argfs
NP_000209.2:p.Leu163fs
NP_001393765.1:p.Leu163Argfs
NP_001393766.1:p.Leu73Argfs
NP_861463.1:p.Leu36Argfs
NP_861463.1:p.Leu36fs
LRG_287t1:c.488del
LRG_287t2:c.107del
LRG_287:g.130648del
LRG_287p2:p.Leu36fs
NC_000011.9:g.2591868del
NC_000011.9:g.2591868delT
NM_000218.2:c.488del
NM_000218.2:c.488delT
NM_181798.1:c.107del
NR_040711.2:n.381delT
p.L163RfsX74
p.Leu163ArgfsX74

Protein change:

L36fs

Links:

dbSNP: rs397508112

NCBI 1000 Genomes Browser:

rs397508112

Molecular consequence:

NM_000218.3:c.488del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.488delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.218delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.107delT - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Congenital long QT syndrome (RWS)
Synonyms:: Familial long QT syndrome; Romano-Ward syndrome; Ventricular fibrillation with prolonged QT interval
Identifiers:: MONDO: MONDO:0019171; MedGen: C1141890; Orphanet: 768; OMIM: PS192500

Name:: Jervell and Lange-Nielsen syndrome (JLNS)
Synonyms:: Jervell-Lange Nielsen syndrome
Identifiers:: MONDO: MONDO:0002441; MedGen: C0022387; OMIM: PS220400

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271231	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Feb 2, 2015)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19716085, 15466642, 15840476, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271231

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Feb 2, 2015)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.

Choi G, Kopplin LJ, Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Circulation. 2004 Oct 12;110(15):2119-24. Epub 2004 Oct 4.

PubMed [citation]

PMID:: 15466642

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271231.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The p.Leu163fs variant in KCNQ1 has been previously reported in at least 1 indiv idual with long QT syndrome and is absent from large population databases (Choi 2004, Tester 2005, Kapplinger 2009). This variant is predicted to cause a frames hift, which alters the protein's amino acid sequence beginning at codon 163 and leads to a premature stop codon 74 amino acids downstream. This alteration is th en predicted to lead to a truncated or absent protein. Loss of function variants in KCNQ1 lead to Jervell and Lange-Nielsen syndrome (JLNS) in compound heterozy gous and homozygous individuals, while dominant-negative and loss-of-function va riants in KCNQ1 have been shown to cause dominantly inherited long QT syndrome 1 (also known as Romano-Ward syndrome)in heterozygous individuals. In summary, al though additional studies are required to fully establish its clinical significa nce, this variant meets our criteria to be classified as likely pathogenic (http ://www.partners.org/personalizedmedicine/LMM) based upon its impact to the prote in.

#	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		1	not provided	1	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine