NM_000218.3(KCNQ1):c.752T>C (p.Leu251Pro) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 16, 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:: RCV001852977.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.752T>C (p.Leu251Pro)]

NM_000218.3(KCNQ1):c.752T>C (p.Leu251Pro)

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.752T>C (p.Leu251Pro)

Other names:

p.L251P:CTG>CCG

HGVS:

NC_000011.10:g.2572081T>C
NG_008935.1:g.132091T>C
NM_000218.3:c.752T>CMANE SELECT
NM_001406836.1:c.752T>C
NM_001406837.1:c.482T>C
NM_181798.2:c.371T>C
NP_000209.2:p.Leu251Pro
NP_000209.2:p.Leu251Pro
NP_001393765.1:p.Leu251Pro
NP_001393766.1:p.Leu161Pro
NP_861463.1:p.Leu124Pro
NP_861463.1:p.Leu124Pro
LRG_287t1:c.752T>C
LRG_287t2:c.371T>C
LRG_287:g.132091T>C
LRG_287p1:p.Leu251Pro
LRG_287p2:p.Leu124Pro
NC_000011.9:g.2593311T>C
NM_000218.2:c.752T>C
NM_181798.1:c.371T>C
NR_040711.2:n.645T>C

Protein change:

L124P

Links:

dbSNP: rs199472716

NCBI 1000 Genomes Browser:

rs199472716

Molecular consequence:

NM_000218.3:c.752T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.752T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.482T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.371T>C - 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
SCV002238482	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 16, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12710526, 10874277, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002238482

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 16, 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

Biophysical characteristics of a new mutation on the KCNQ1 potassium channel (L251P) causing long QT syndrome.

Deschênes D, Acharfi S, Pouliot V, Hegele R, Krahn A, Daleau P, Chahine M.

Can J Physiol Pharmacol. 2003 Feb;81(2):129-34.

PubMed [citation]

PMID:: 12710526

A novel mutation in KVLQT1, L122P, found in a family with autosomal dominant long QT syndrome.

Krahn AD, Wang J, Spindler B, Skanes AC, Yee R, Klein GJ, Hegele RA.

Am Heart J. 2000 Jul;140(1):146-9.

PubMed [citation]

PMID:: 10874277

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238482.3

#	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 been reported to affect KCNQ1 protein function (PMID: 12710526). This variant has been observed to be de novo in an individual affected with long QT syndrome (LQTS) and segregated with LQTS in this individual's children (PMID: 10874277). This variant is also known as L122P in the literature. ClinVar contains an entry for this variant (Variation ID: 53095). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 251 of the KCNQ1 protein (p.Leu251Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.

#	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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