NM_000218.3(KCNQ1):c.1354del (p.Arg452fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 13, 2023
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:: RCV001929608.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1354del (p.Arg452fs)]

NM_000218.3(KCNQ1):c.1354del (p.Arg452fs)

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.1354del (p.Arg452fs)

HGVS:

NC_000011.10:g.2588815del
NG_008935.1:g.148825del
NM_000218.3:c.1354delMANE SELECT
NM_001406836.1:c.1258delC
NM_001406837.1:c.1084delC
NM_001406838.1:c.814delC
NM_181798.2:c.973delC
NP_000209.2:p.Arg452Glyfs
NP_000209.2:p.Arg452fs
NP_001393765.1:p.Arg420Glyfs
NP_001393766.1:p.Arg362Glyfs
NP_001393767.1:p.Arg272Glyfs
NP_861463.1:p.Arg325Glyfs
NP_861463.1:p.Arg325fs
LRG_287t1:c.1354del
LRG_287t2:c.973del
LRG_287:g.148825del
LRG_287p1:p.Arg452Glyfs
LRG_287p2:p.Arg325fs
NC_000011.9:g.2610045del
NM_000218.2:c.1354delC
NM_181798.1:c.973del
NR_040711.2:n.1247delC

Protein change:

R325fs

Links:

dbSNP: rs2133760795

NCBI 1000 Genomes Browser:

rs2133760795

Molecular consequence:

NM_000218.3:c.1354del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.1258delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.1084delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406838.1:c.814delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.973delC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002206060	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9323054, 19862833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002206060

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.

Shalaby FY, Levesque PC, Yang WP, Little WA, Conder ML, Jenkins-West T, Blanar MA.

Circulation. 1997 Sep 16;96(6):1733-6.

PubMed [citation]

PMID:: 9323054

The genetic basis of long QT and short QT syndromes: a mutation update.

Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M.

Hum Mutat. 2009 Nov;30(11):1486-511. doi: 10.1002/humu.21106. Review.

PubMed [citation]

PMID:: 19862833

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002206060.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1426804). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg452Glyfs*14) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833).

#	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: Sep 29, 2024

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