NM_172201.2(KCNE2):c.170T>C (p.Ile57Thr) AND Long QT syndrome 6

Germline classification:: Conflicting interpretations of pathogenicity (7 submissions)
Last evaluated:: Dec 30, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000006426.32

Allele description [Variation Report for NM_172201.2(KCNE2):c.170T>C (p.Ile57Thr)]

NM_172201.2(KCNE2):c.170T>C (p.Ile57Thr)

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.170T>C (p.Ile57Thr)

Other names:

p.I57T:ATT>ACT

HGVS:

NC_000021.9:g.34370648T>C
NG_008804.1:g.11625T>C
NM_172201.2:c.170T>CMANE SELECT
NP_751951.1:p.Ile57Thr
NP_751951.1:p.Ile57Thr
LRG_291t1:c.170T>C
LRG_291:g.11625T>C
LRG_291p1:p.Ile57Thr
NC_000021.8:g.35742947T>C
NM_172201.1:c.170T>C
Q9Y6J6:p.Ile57Thr

Protein change:

I57T; ILE57THR

Links:

UniProtKB: Q9Y6J6#VAR_008378; OMIM: 603796.0003; dbSNP: rs74315448

NCBI 1000 Genomes Browser:

rs74315448

Molecular consequence:

NM_172201.2:c.170T>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

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
SCV000026609	OMIM	no assertion criteria provided	Pathogenic (Apr 16, 1999)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000560071	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Dec 30, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000805126	Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 27, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000883147	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 21, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001192584	Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	no assertion criteria provided	Uncertain significance (Jun 25, 2019)	germline	clinical testing
SCV001299550	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20042375, 19841298, 10219239 Citation Link,
SCV001367021	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 24, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders.

Wu J, Shimizu W, Ding WG, Ohno S, Toyoda F, Itoh H, Zang WJ, Miyamoto Y, Kamakura S, Matsuura H, Nademanee K, Brugada J, Brugada P, Brugada R, Vatta M, Towbin JA, Antzelevitch C, Horie M.

Heart Rhythm. 2010;7(2):199-205. doi: 10.1016/j.hrthm.2009.10.012. Epub 2009 Oct 12.

PubMed [citation]

PMID:: 20042375
PMCID:: PMC2819024

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000026609.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a healthy 48-year-old Hispanic female with no history of torsade de pointes or ventricular fibrillation, Abbott et al. (1999) identified a T-to-C transition at nucleotide 170, resulting in an ile57-to-thr substitution in the predicted transmembrane segment of MiRP1. The patient's resting electrocardiogram showed a prolonged QT interval (QTc = 470 ms) (613693).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000560071.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	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

From Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues, SCV000805126.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000883147.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare, SCV001192584.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001299550.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001367021.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BS1.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

Relating variation to medicine