NM_000218.3(KCNQ1):c.533delinsGG (p.Ala178fs) AND Long QT syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 10, 2004
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000003297.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.533delinsGG (p.Ala178fs)]

NM_000218.3(KCNQ1):c.533delinsGG (p.Ala178fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.533delinsGG (p.Ala178fs)

HGVS:

NC_000011.10:g.2570683delinsGG
NG_008935.1:g.130693delinsGG
NM_000218.3:c.533delinsGGMANE SELECT
NM_001406836.1:c.533delCinsGG
NM_001406837.1:c.263delCinsGG
NM_181798.2:c.152delCinsGG
NP_000209.2:p.Ala178Glyfs
NP_000209.2:p.Ala178fs
NP_001393765.1:p.Ala178Glyfs
NP_001393766.1:p.Ala88Glyfs
NP_861463.1:p.Ala51Glyfs
NP_861463.1:p.Ala51fs
LRG_287t1:c.533delCinsGG
LRG_287t2:c.152delinsGG
LRG_287:g.130693delinsGG
LRG_287p1:p.Ala178Glyfs
LRG_287p2:p.Ala51fs
NC_000011.9:g.2591913delinsGG
NM_000218.2:c.533delCinsGG
NM_181798.1:c.152delinsGG
NR_040711.2:n.426delCinsGG

Protein change:

A178fs

Links:

OMIM: 607542.0036; dbSNP: rs397508115

NCBI 1000 Genomes Browser:

rs397508115

Molecular consequence:

NM_000218.3:c.533delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.533delCinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.263delCinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.152delCinsGG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Long QT syndrome 1 (LQT1)
Identifiers:: MONDO: MONDO:0100316; MedGen: C4551647; Orphanet: 101016; Orphanet: 768; OMIM: 192500

Recent activity

Clear Turn Off Turn On

SAMN32802002 (1)
SRA
Paramunida longior isolate PAR47 cytochrome oxidase subunit I (COI) gene, partia...
Paramunida longior isolate PAR47 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|311034478|gb|GU814912.1|

Nucleotide
Paramunida longior isolate PAR48 16S ribosomal RNA gene, partial sequence; mitoc...
Paramunida longior isolate PAR48 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|311501743|gb|HM173487.1|

Nucleotide
Paramunida longior isolate PAR46 cytochrome oxidase subunit I (COI) gene, partia...
Paramunida longior isolate PAR46 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|311034476|gb|GU814911.1|

Nucleotide
Paramunida longior isolate PAR38 16S ribosomal RNA gene, partial sequence; mitoc...
Paramunida longior isolate PAR38 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|311501733|gb|HM173477.1|

Nucleotide

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
SCV000023455	OMIM	no assertion criteria provided	Pathogenic (Sep 10, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023455

OMIM

no assertion criteria provided

Pathogenic
(Sep 10, 2004)

germline

literature only

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect.

Aizawa Y, Ueda K, Wu LM, Inagaki N, Hayashi T, Takahashi M, Ohta M, Kawano S, Hirano Y, Yasunami M, Aizawa Y, Kimura A, Hiraoka M.

FEBS Lett. 2004 Sep 10;574(1-3):145-50.

PubMed [citation]

PMID:: 15358555

Details of each submission

From OMIM, SCV000023455.2

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

Description

In a 13-year-old girl with long QT syndrome (192500), Aizawa et al. (2004) identified a C-to-GG substitution at nucleotide 533 in the KCNQ1 gene, causing a frameshift at alanine-178 and resulting in a truncated protein with elimination of the S3 to S6 domains and the C terminus of the KCNQ1 channel. Coexpression experiments in COS-7 cells showed that mutant and wildtype KCNQ1 remained within the cytoplasm rather than being distributed to the plasma membrane, suggesting that the truncated mutant forms a heteromultimer with wildtype KCNQ1 and causes a dominant-negative effect due to a trafficking defect.

#	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

Last Updated: Mar 26, 2023

ClinVar

Relating variation to medicine