NM_000218.3(KCNQ1):c.1349A>G (p.Glu450Gly) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 9, 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:: RCV002521457.10

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1349A>G (p.Glu450Gly)]

NM_000218.3(KCNQ1):c.1349A>G (p.Glu450Gly)

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.1349A>G (p.Glu450Gly)

HGVS:

NC_000011.10:g.2588810A>G
NG_008935.1:g.148820A>G
NM_000218.3:c.1349A>GMANE SELECT
NM_001406836.1:c.1253A>G
NM_001406837.1:c.1079A>G
NM_001406838.1:c.809A>G
NM_181798.2:c.968A>G
NP_000209.2:p.Glu450Gly
NP_000209.2:p.Glu450Gly
NP_001393765.1:p.Glu418Gly
NP_001393766.1:p.Glu360Gly
NP_001393767.1:p.Glu270Gly
NP_861463.1:p.Glu323Gly
NP_861463.1:p.Glu323Gly
LRG_287t1:c.1349A>G
LRG_287t2:c.968A>G
LRG_287:g.148820A>G
LRG_287p1:p.Glu450Gly
LRG_287p2:p.Glu323Gly
NC_000011.9:g.2610040A>G
NM_000218.2:c.1349A>G
NM_181798.1:c.968A>G
NR_040711.2:n.1242A>G

Protein change:

E270G

Links:

dbSNP: rs1057518902

NCBI 1000 Genomes Browser:

rs1057518902

Molecular consequence:

NM_000218.3:c.1349A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.1253A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.1079A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.809A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.968A>G - 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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hypothetical protein [Actinomycetes bacterium]
hypothetical protein [Actinomycetes bacterium]
gi|2650931188|gb|WRX71497.1|

Protein
PREDICTED: Homo sapiens neurexin 3 (NRXN3), transcript variant X1, mRNA
PREDICTED: Homo sapiens neurexin 3 (NRXN3), transcript variant X1, mRNA
gi|2217298964|ref|XM_011537363.2|

Nucleotide
serine/threonine-protein kinase Sgk3 isoform 1 [Homo sapiens]
serine/threonine-protein kinase Sgk3 isoform 1 [Homo sapiens]
gi|75813626|ref|NP_001028750.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003025743	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 9, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003025743

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 9, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV003025743.2

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

Description

This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ1 protein function. ClinVar contains an entry for this variant (Variation ID: 374106). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 450 of the KCNQ1 protein (p.Glu450Gly).

#	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: Nov 3, 2024

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