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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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001533993Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 10, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024