NM_000218.3(KCNQ1):c.1025T>A (p.Leu342His) AND Long QT syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 12, 2017
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:: RCV000470879.8

Allele description

NM_000218.3(KCNQ1):c.1025T>A (p.Leu342His)

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.1025T>A (p.Leu342His)

HGVS:

NC_000011.10:g.2583538T>A
NG_008935.1:g.143548T>A
NM_000218.3:c.1025T>AMANE SELECT
NM_001406836.1:c.1025T>A
NM_001406837.1:c.755T>A
NM_001406838.1:c.581T>A
NM_181798.2:c.644T>A
NP_000209.2:p.Leu342His
NP_000209.2:p.Leu342His
NP_001393765.1:p.Leu342His
NP_001393766.1:p.Leu252His
NP_001393767.1:p.Leu194His
NP_861463.1:p.Leu215His
NP_861463.1:p.Leu215His
LRG_287t1:c.1025T>A
LRG_287t2:c.644T>A
LRG_287:g.143548T>A
LRG_287p1:p.Leu342His
LRG_287p2:p.Leu215His
NC_000011.9:g.2604768T>A
NM_000218.2:c.1025T>A
NM_181798.1:c.644T>A
NR_040711.2:n.918T>A

Protein change:

L194H

Links:

dbSNP: rs794728522

NCBI 1000 Genomes Browser:

rs794728522

Molecular consequence:

NM_000218.3:c.1025T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.1025T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.755T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.581T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.644T>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000543317	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 12, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19841300, 25348405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000543317

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 12, 2017)

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

Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ.

Circulation. 2009 Nov 3;120(18):1752-60. doi: 10.1161/CIRCULATIONAHA.109.863076. Epub 2009 Oct 19.

PubMed [citation]

PMID:: 19841300
PMCID:: PMC3025752

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]

PMID:: 25348405
PMCID:: PMC4384041

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000543317.5

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant identified in the KCNQ1 gene is located in the transmembrane S6 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNQ1-topology. It is unclear how this variant impacts the function of this protein. This variant has not been reported in the literature in individuals with a KCNQ1-related disease. ClinVar contains an entry for this variant (Variation ID: 405269). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with histidine at codon 342 of the KCNQ1 protein (p.Leu342His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine.

#	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: May 1, 2024

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