NM_000218.3(KCNQ1):c.850_852del (p.Glu284del) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 8, 2023
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:: RCV001248259.8

Allele description [Variation Report for NM_000218.3(KCNQ1):c.850_852del (p.Glu284del)]

NM_000218.3(KCNQ1):c.850_852del (p.Glu284del)

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.850_852del (p.Glu284del)

HGVS:

NC_000011.10:g.2572915_2572917del
NG_008935.1:g.132925_132927del
NM_000218.3:c.850_852delMANE SELECT
NM_001406836.1:c.850_852delGAG
NM_001406837.1:c.580_582delGAG
NM_181798.2:c.469_471delGAG
NP_000209.2:p.Glu284del
NP_000209.2:p.Glu284del
NP_000209.2:p.Glu284del
NP_001393765.1:p.Glu284del
NP_001393766.1:p.Glu194del
NP_861463.1:p.Glu157del
NP_861463.1:p.Glu157del
LRG_287t1:c.850_852del
LRG_287t2:c.469_471del
LRG_287:g.132925_132927del
LRG_287p1:p.Glu284del
LRG_287p2:p.Glu157del
NC_000011.9:g.2594145_2594147del
NM_000218.2:c.850_852del
NM_000218.2:c.850_852delGAG
NM_181798.1:c.469_471del
NR_040711.2:n.743_745delGAG

Protein change:

E157del

Links:

dbSNP: rs1064796353

NCBI 1000 Genomes Browser:

rs1064796353

Molecular consequence:

NM_000218.3:c.850_852del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406836.1:c.850_852delGAG - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406837.1:c.580_582delGAG - inframe_indel - [Sequence Ontology: SO:0001820]
NM_181798.2:c.469_471delGAG - inframe_indel - [Sequence Ontology: SO:0001820]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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
SCV001421730	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14678125, 17470695, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001421730

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (3)
[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

Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome.

Zareba W, Moss AJ, Sheu G, Kaufman ES, Priori S, Vincent GM, Towbin JA, Benhorin J, Schwartz PJ, Napolitano C, Hall WJ, Keating MT, Qi M, Robinson J, Andrews ML; International LQTS Registry, University of Rochester, Rochester, New York..

J Cardiovasc Electrophysiol. 2003 Nov;14(11):1149-53.

PubMed [citation]

PMID:: 14678125

Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.

Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S.

Circulation. 2007 May 15;115(19):2481-9. Epub 2007 Apr 30.

PubMed [citation]

PMID:: 17470695
PMCID:: PMC3332528

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001421730.5

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

Description

This variant disrupts a region of the KCNQ1 protein in which other variant(s) (p.Glu284Lys) have been determined to be pathogenic (PMID: 14678125, 17470695; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 423306). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.850_852del, results in the deletion of 1 amino acid(s) of the KCNQ1 protein (p.Glu284del), but otherwise preserves the integrity of the reading frame.

#	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