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NM_172201.2(KCNE2):c.67A>T (p.Met23Leu) AND Long QT syndrome 6

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 27, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000678938.10

Allele description [Variation Report for NM_172201.2(KCNE2):c.67A>T (p.Met23Leu)]

NM_172201.2(KCNE2):c.67A>T (p.Met23Leu)

Genes:
KCNE2:potassium voltage-gated channel subfamily E regulatory subunit 2 [Gene - OMIM - HGNC]
LOC105372791:uncharacterized LOC105372791 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.11
Genomic location:
Preferred name:
NM_172201.2(KCNE2):c.67A>T (p.Met23Leu)
HGVS:
  • NC_000021.9:g.34370545A>T
  • NG_008804.1:g.11522A>T
  • NM_172201.2:c.67A>TMANE SELECT
  • NP_751951.1:p.Met23Leu
  • NP_751951.1:p.Met23Leu
  • LRG_291t1:c.67A>T
  • LRG_291:g.11522A>T
  • LRG_291p1:p.Met23Leu
  • NC_000021.8:g.35742844A>T
  • NM_172201.1:c.67A>T
Protein change:
M23L
Links:
dbSNP: rs747045005
NCBI 1000 Genomes Browser:
rs747045005
Molecular consequence:
  • NM_172201.2:c.67A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 6 (LQT6)
Identifiers:
MONDO: MONDO:0013370; MedGen: C3150953; Orphanet: 101016; Orphanet: 768; OMIM: 613693

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000805150Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 8, 2018) 		unknownclinical testing

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

SCV000828794Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 27, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.

Olesen MS, Andreasen L, Jabbari J, Refsgaard L, Haunsø S, Olesen SP, Nielsen JB, Schmitt N, Svendsen JH.

Heart Rhythm. 2014 Feb;11(2):246-51. doi: 10.1016/j.hrthm.2013.10.034. Epub 2013 Oct 18.

PubMed [citation]
PMID:
24144883
See all PubMed Citations (4)

Details of each submission

From Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues, SCV000805150.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828794.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces methionine with leucine at codon 23 of the KCNE2 protein (p.Met23Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs747045005, ExAC 0.003%). This missense change has been observed in individual(s) with early-onset lone atrial fibrillation (PMID: 24144883, 24796621). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects KCNE2 function (PMID: 24796621). 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: Oct 20, 2024