NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2021
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:: RCV001970148.6

Allele description [Variation Report for NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)]

NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)

HGVS:

NC_000011.10:g.2572074_2572075dup
NG_008935.1:g.132084_132085dup
NM_000218.3:c.745_746dupMANE SELECT
NM_001406836.1:c.745_746dup
NM_001406837.1:c.475_476dup
NM_181798.2:c.364_365dup
NP_000209.2:p.Leu250Glyfs
NP_000209.2:p.Leu250fs
NP_001393765.1:p.Leu250Glyfs
NP_001393766.1:p.Leu160Glyfs
NP_861463.1:p.Leu123Glyfs
NP_861463.1:p.Leu123fs
LRG_287t1:c.745_746dup
LRG_287t2:c.364_365dup
LRG_287:g.132084_132085dup
LRG_287p1:p.Leu250Glyfs
LRG_287p2:p.Leu123fs
NC_000011.9:g.2593302_2593303insGA
NC_000011.9:g.2593304_2593305dup
NM_000218.2:c.745_746dup
NM_181798.1:c.364_365dup
NR_040711.2:n.638_639dup

Protein change:

L123fs

Links:

dbSNP: rs1221462654

NCBI 1000 Genomes Browser:

rs1221462654

Molecular consequence:

NM_000218.3:c.745_746dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.745_746dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.475_476dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.364_365dup - 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
SCV002229367	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2021)	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

SCV002229367

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 2021)

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, SCV002229367.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with KCNQ1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu250Glyfs*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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