NM_000218.3(KCNQ1):c.562T>C (p.Trp188Arg) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 10, 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:: RCV003647395.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.562T>C (p.Trp188Arg)]

NM_000218.3(KCNQ1):c.562T>C (p.Trp188Arg)

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.562T>C (p.Trp188Arg)

HGVS:

NC_000011.10:g.2570712T>C
NG_008935.1:g.130722T>C
NM_000218.3:c.562T>CMANE SELECT
NM_001406836.1:c.562T>C
NM_001406837.1:c.292T>C
NM_001406838.1:c.478-12723T>C
NM_181798.2:c.181T>C
NP_000209.2:p.Trp188Arg
NP_000209.2:p.Trp188Arg
NP_001393765.1:p.Trp188Arg
NP_001393766.1:p.Trp98Arg
NP_861463.1:p.Trp61Arg
NP_861463.1:p.Trp61Arg
LRG_287t1:c.562T>C
LRG_287t2:c.181T>C
LRG_287:g.130722T>C
LRG_287p1:p.Trp188Arg
LRG_287p2:p.Trp61Arg
NC_000011.9:g.2591942T>C
NM_000218.2:c.562T>C
NM_181798.1:c.181T>C
NR_040711.2:n.455T>C

Protein change:

W188R

Molecular consequence:

NM_001406838.1:c.478-12723T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000218.3:c.562T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.562T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.292T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.181T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Mus musculus calmegin (Clgn), transcript variant 1, mRNA
Mus musculus calmegin (Clgn), transcript variant 1, mRNA
gi|1046552718|ref|NM_009904.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004391999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26469389, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004391999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 10, 2023)

germline

clinical testing

PubMed (2)
[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

Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation.

Chen L, Zhang Q, Qiu Y, Li Z, Chen Z, Jiang H, Li Y, Yang H.

Sci Rep. 2015 Oct 15;5:15079. doi: 10.1038/srep15079.

PubMed [citation]

PMID:: 26469389
PMCID:: PMC4606798

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004391999.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 188 of the KCNQ1 protein (p.Trp188Arg). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNQ1 protein function. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 26469389). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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