NM_000218.3(KCNQ1):c.743G>A (p.Trp248Ter) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 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:: RCV001061339.7

Allele description [Variation Report for NM_000218.3(KCNQ1):c.743G>A (p.Trp248Ter)]

NM_000218.3(KCNQ1):c.743G>A (p.Trp248Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.743G>A (p.Trp248Ter)

HGVS:

NC_000011.10:g.2572072G>A
NG_008935.1:g.132082G>A
NM_000218.3:c.743G>AMANE SELECT
NM_001406836.1:c.743G>A
NM_001406837.1:c.473G>A
NM_181798.2:c.362G>A
NP_000209.2:p.Trp248Ter
NP_000209.2:p.Trp248Ter
NP_001393765.1:p.Trp248Ter
NP_001393766.1:p.Trp158Ter
NP_861463.1:p.Trp121Ter
NP_861463.1:p.Trp121Ter
LRG_287t1:c.743G>A
LRG_287t2:c.362G>A
LRG_287:g.132082G>A
LRG_287p1:p.Trp248Ter
LRG_287p2:p.Trp121Ter
NC_000011.9:g.2593302G>A
NM_000218.2:c.743G>A
NM_181798.1:c.362G>A
NR_040711.2:n.636G>A

Protein change:

W121*

Links:

dbSNP: rs1848344878

NCBI 1000 Genomes Browser:

rs1848344878

Molecular consequence:

NM_000218.3:c.743G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406836.1:c.743G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406837.1:c.473G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_181798.2:c.362G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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C4025863[conceptid] (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226077	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 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

SCV001226077

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 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, SCV001226077.5

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

Description

This sequence change creates a premature translational stop signal (p.Trp248*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 855976). For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine