NM_172201.2(KCNE2):c.193G>C (p.Val65Leu) AND Long QT syndrome 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2021
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:: RCV000228047.6

Allele description [Variation Report for NM_172201.2(KCNE2):c.193G>C (p.Val65Leu)]

NM_172201.2(KCNE2):c.193G>C (p.Val65Leu)

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.193G>C (p.Val65Leu)

HGVS:

NC_000021.9:g.34370671G>C
NG_008804.1:g.11648G>C
NM_172201.2:c.193G>CMANE SELECT
NP_751951.1:p.Val65Leu
NP_751951.1:p.Val65Leu
LRG_291t1:c.193G>C
LRG_291:g.11648G>C
LRG_291p1:p.Val65Leu
NC_000021.8:g.35742970G>C
NM_172201.1:c.193G>C
Q9Y6J6:p.Val65Leu

Protein change:

V65L

Links:

UniProtKB: Q9Y6J6#VAR_074924; dbSNP: rs199473364

NCBI 1000 Genomes Browser:

rs199473364

Molecular consequence:

NM_172201.2:c.193G>C - 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

Recent activity

Clear Turn Off Turn On

programmed cell death protein 2 isoform 4 [Homo sapiens]
programmed cell death protein 2 isoform 4 [Homo sapiens]
gi|313851173|ref|NP_001186391.1|

Protein
double homeobox protein 5 [Homo sapiens]
double homeobox protein 5 [Homo sapiens]
gi|207442670|ref|NP_036281.2|

Protein
Diet, Vegan
Diet, Vegan
Dietary practice of avoiding animal products in any form.<br/>Year introduced: 2016

MeSH
Conscientious Refusal to Treat
Conscientious Refusal to Treat
Refusal of health professionals to provide medical services on the basis of moral or religious beliefs.<br/>

MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291573	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	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

SCV000291573

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

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, SCV000291573.4

#	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 valine with leucine at codon 65 of the KCNE2 protein (p.Val65Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs199473364, ExAC 0.03%). This missense change has been observed in individual(s) with suspected LQTS (PMID: 19716085). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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

ClinVar

Relating variation to medicine