NM_000219.6(KCNE1):c.247G>A (p.Glu83Lys) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 2022
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:: RCV001340194.5

Allele description [Variation Report for NM_000219.6(KCNE1):c.247G>A (p.Glu83Lys)]

NM_000219.6(KCNE1):c.247G>A (p.Glu83Lys)

Gene:

KCNE1:potassium voltage-gated channel subfamily E regulatory subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_000219.6(KCNE1):c.247G>A (p.Glu83Lys)

HGVS:

NC_000021.9:g.34449388C>T
NG_009091.1:g.66928G>A
NM_000219.6:c.247G>AMANE SELECT
NM_001127668.4:c.247G>A
NM_001127669.4:c.247G>A
NM_001127670.4:c.247G>A
NM_001270402.3:c.247G>A
NM_001270403.2:c.247G>A
NM_001270404.3:c.247G>A
NM_001270405.3:c.247G>A
NP_000210.2:p.Glu83Lys
NP_001121140.1:p.Glu83Lys
NP_001121141.1:p.Glu83Lys
NP_001121142.1:p.Glu83Lys
NP_001257331.1:p.Glu83Lys
NP_001257332.1:p.Glu83Lys
NP_001257333.1:p.Glu83Lys
NP_001257334.1:p.Glu83Lys
LRG_290t1:c.247G>A
LRG_290:g.66928G>A
NC_000021.8:g.35821686C>T
NM_000219.3:c.247G>A
NM_001127670.4:c.247G>A
P15382:p.Glu83Lys

Protein change:

E83K

Links:

UniProtKB: P15382#VAR_074919; dbSNP: rs199473360

NCBI 1000 Genomes Browser:

rs199473360

Molecular consequence:

NM_000219.6:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Effect on ion channel function [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0001] - Comment(s)

Condition(s)

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

Recent activity

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inhibitor of Bruton agammaglobulinemia tyrosine kinase, isoform CRA_d [Homo sapi...
inhibitor of Bruton agammaglobulinemia tyrosine kinase, isoform CRA_d [Homo sapiens]
gi|119569073|gb|EAW48688.1||gnl|WGS |hCP1877285

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001533993	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001533993

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2022)

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

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

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, SCV001533993.3

#	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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 83 of the KCNE1 protein (p.Glu83Lys). This variant is present in population databases (rs199473360, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of KCNE1-related conditions (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 132673). 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 KCNE1 protein function. 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: Nov 10, 2024

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