NM_000218.3(KCNQ1):c.32A>G (p.Glu11Gly) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 20, 2024
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:: RCV003534092.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.32A>G (p.Glu11Gly)]

NM_000218.3(KCNQ1):c.32A>G (p.Glu11Gly)

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.32A>G (p.Glu11Gly)

HGVS:

NC_000011.10:g.2445130A>G
NG_008935.1:g.5140A>G
NM_000218.3:c.32A>GMANE SELECT
NM_001406836.1:c.32A>G
NM_001406837.1:c.-331A>G
NM_001406838.1:c.32A>G
NP_000209.2:p.Glu11Gly
NP_000209.2:p.Glu11Gly
NP_001393765.1:p.Glu11Gly
NP_001393767.1:p.Glu11Gly
LRG_287t1:c.32A>G
LRG_287:g.5140A>G
LRG_287p1:p.Glu11Gly
NC_000011.9:g.2466360A>G
NM_000218.2:c.32A>G

Protein change:

E11G

Molecular consequence:

NM_001406837.1:c.-331A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000218.3:c.32A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.32A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.32A>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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translation elongation factor EF-1 alpha, partial [Lamproderma pseudomaculatum]
translation elongation factor EF-1 alpha, partial [Lamproderma pseudomaculatum]
gi|2306687660|gb|UXE43990.1|

Protein
Otomys cf. saundersiae voucher DM8395 cytochrome b gene, partial cds; mitochondr...
Otomys cf. saundersiae voucher DM8395 cytochrome b gene, partial cds; mitochondrial
gi|229558135|gb|FJ619542.1|

Nucleotide
Beaded filament structural protein 2, phakinin [Mus musculus]
Beaded filament structural protein 2, phakinin [Mus musculus]
gi|45768764|gb|AAH68172.1|

Protein
unnamed protein product [Mus musculus]
unnamed protein product [Mus musculus]
gi|74147854|dbj|BAE22294.1|

Protein
Rhizopogon sp. pineroot_b25_mb402 internal transcribed spacer 1, partial sequenc...
Rhizopogon sp. pineroot_b25_mb402 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|669296766|gb|KF428715.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004264322	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 20, 2024)	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

SCV004264322

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 20, 2024)

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, SCV004264322.1

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 11 of the KCNQ1 protein (p.Glu11Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. 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 expected to disrupt KCNQ1 protein function with a positive predictive value of 95%. 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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