NM_000218.3(KCNQ1):c.919G>T (p.Val307Leu) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 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:: RCV001065918.9

Allele description [Variation Report for NM_000218.3(KCNQ1):c.919G>T (p.Val307Leu)]

NM_000218.3(KCNQ1):c.919G>T (p.Val307Leu)

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.919G>T (p.Val307Leu)

HGVS:

NC_000011.10:g.2572984G>T
NG_008935.1:g.132994G>T
NM_000218.3:c.919G>TMANE SELECT
NM_001406836.1:c.919G>T
NM_001406837.1:c.649G>T
NM_181798.2:c.538G>T
NP_000209.2:p.Val307Leu
NP_000209.2:p.Val307Leu
NP_001393765.1:p.Val307Leu
NP_001393766.1:p.Val217Leu
NP_861463.1:p.Val180Leu
NP_861463.1:p.Val180Leu
LRG_287t1:c.919G>T
LRG_287t2:c.538G>T
LRG_287:g.132994G>T
LRG_287p1:p.Val307Leu
LRG_287p2:p.Val180Leu
NC_000011.9:g.2594214G>T
NM_000218.2:c.919G>T
NM_181798.1:c.538G>T
NR_040711.2:n.812G>T

Protein change:

V180L

Links:

dbSNP: rs120074195

NCBI 1000 Genomes Browser:

rs120074195

Molecular consequence:

NM_000218.3:c.919G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.919G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.649G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.538G>T - 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
SCV001230908	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11278406, 15159330, 19862833, 20436212, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001230908

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2023)

germline

clinical testing

PubMed (5)
[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

Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome.

Seebohm G, Scherer CR, Busch AE, Lerche C.

J Biol Chem. 2001 Apr 27;276(17):13600-5. Epub 2001 Jan 17.

PubMed [citation]

PMID:: 11278406

Mutation in the KCNQ1 gene leading to the short QT-interval syndrome.

Bellocq C, van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens MM, Baró I, Wilde AA.

Circulation. 2004 May 25;109(20):2394-7.

PubMed [citation]

PMID:: 15159330

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001230908.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 307 of the KCNQ1 protein (p.Val307Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with short QT syndrome (PMID: 15159330). ClinVar contains an entry for this variant (Variation ID: 859740). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 11278406, 15159330, 19862833, 20436212). 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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