NM_000218.3(KCNQ1):c.1588C>T (p.Gln530Ter) AND Cardiac arrhythmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 18, 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:: RCV001841634.11

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1588C>T (p.Gln530Ter)]

NM_000218.3(KCNQ1):c.1588C>T (p.Gln530Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.1588C>T (p.Gln530Ter)

Other names:

p.Q530*:CAG>TAG; p.Gln530*

HGVS:

NC_000011.10:g.2768917C>T
NG_008935.1:g.328927C>T
NM_000218.3:c.1588C>TMANE SELECT
NM_001406836.1:c.1492C>T
NM_001406837.1:c.1318C>T
NM_001406838.1:c.1048C>T
NM_181798.2:c.1207C>T
NP_000209.2:p.Gln530Ter
NP_000209.2:p.Gln530Ter
NP_001393765.1:p.Gln498Ter
NP_001393766.1:p.Gln440Ter
NP_001393767.1:p.Gln350Ter
NP_861463.1:p.Gln403Ter
NP_861463.1:p.Gln403Ter
LRG_287t1:c.1588C>T
LRG_287t2:c.1207C>T
LRG_287:g.328927C>T
LRG_287p1:p.Gln530Ter
LRG_287p2:p.Gln403Ter
NC_000011.9:g.2790147C>T
NM_000218.2:c.1588C>T
NM_181798.1:c.1207C>T
NR_040711.2:n.1481C>T

Protein change:

Q350*

Links:

dbSNP: rs397508097

NCBI 1000 Genomes Browser:

rs397508097

Molecular consequence:

NM_000218.3:c.1588C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406836.1:c.1492C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406837.1:c.1318C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406838.1:c.1048C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181798.2:c.1207C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001355739	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 18, 2023)	germline	clinical testing	PubMed (16) [See all records that cite these PMIDs] 10704188, 10973849, 11530100, 14510661, 14678125, 15051636, 18752142, 19716085, 22629021, 23392653, 24552659, 24606995, 24912595, 25705178, 27451284, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001355739

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 18, 2023)

germline

clinical testing

PubMed (16)
[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

Jervell and Lange-Nielsen syndrome: a Norwegian perspective.

Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M.

Am J Med Genet. 1999 Sep 24;89(3):137-46. Review.

PubMed [citation]

PMID:: 10704188

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]

PMID:: 10973849

See all PubMed Citations (16)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001355739.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

This variant creates a premature translation stop signal in exon 12 of the KCNQ1 protein. This variant is expected to result in an absent or non-functional protein product. Functional studies have shown that the variant causes defective trafficking to the cell membrane and non-functional potassium channel (PMID: 15051636, 24912595, 25705178). This variant has been reported in the heterozygous state in more than 50 individuals affected with long QT syndrome (PMID: 10973849, 14678125, 18752142, 19716085, 22629021, 23392653, 24552659, 24606995, 27451284) and in the homozygous or compound heterozygous state in more than 20 individuals affected with Jervell and Lange-Nielsen syndrome (PMID: 10704188, 10973849, 11530100, 14510661, 18752142, 23392653, 22629021). This variant has been identified in 7/251292 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of KCNQ1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.

#	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 16, 2024

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