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NM_172201.1(KCNE2):c.79C>T (p.Arg27Cys) AND Long QT syndrome 6

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 11, 2017
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:
RCV000576237.1

Allele description

NM_172201.1(KCNE2):c.79C>T (p.Arg27Cys)

Gene:
KCNE2:potassium voltage-gated channel subfamily E regulatory subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.11
Genomic location:
Preferred name:
NM_172201.1(KCNE2):c.79C>T (p.Arg27Cys)
HGVS:
  • NC_000021.9:g.34370557C>T
  • NG_008804.1:g.11534C>T
  • NM_172201.1:c.79C>T
  • NP_751951.1:p.Arg27Cys
  • LRG_291t1:c.79C>T
  • LRG_291:g.11534C>T
  • LRG_291p1:p.Arg27Cys
  • NC_000021.8:g.35742856C>T
  • Q9Y6J6:p.Arg27Cys
Protein change:
R27C; ARG27CYS
Links:
NCBI 1000 Genomes Browser:
rs74315449
Molecular consequence:
  • NM_172201.1:c.79C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 6 (LQT6)
Identifiers:
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
SCV000677060Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 11, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000677060.1

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

Description

This sequence change replaces arginine with cysteine at codon 27 of the KCNE2 protein (p.Arg27Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs74315449, ExAC 0.05%). This variant has been reported in two families affected with atrial fibrillation as well as in unaffected family members (PMID: 15368194). It was also observed in a healthy control individual (PMID: 16487223). ClinVar contains an entry for this variant (Variation ID: 6055). Experimental studies have shown that this missense change affects protein function causing an increase in KCNQ1-KCNE2 voltage density and enhancing suppression of the cardiac L type calcium channel  (PMID: 15368194, 24681347). In summary, this variant segregates with disease and disrupts protein function in vitro. However, it has been observed in healthy controls and is present in the population at an appreciable frequency.  For these reasons, this change 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 2, 2019