U.S. flag

An official website of the United States government

NM_000218.3(KCNQ1):c.1893del (p.Arg632fs) AND Cardiac arrhythmia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 29, 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:
RCV001841641.12

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1893del (p.Arg632fs)]

NM_000218.3(KCNQ1):c.1893del (p.Arg632fs)

Genes:
KCNQ1-AS1:KCNQ1 antisense RNA 1 [Gene - HGNC]
KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000218.3(KCNQ1):c.1893del (p.Arg632fs)
HGVS:
  • NC_000011.10:g.2847865del
  • NG_008935.1:g.407875del
  • NM_000218.3:c.1893delMANE SELECT
  • NM_001406836.1:c.1797delC
  • NM_001406837.1:c.1623delC
  • NM_001406838.1:c.1353delC
  • NM_001406839.1:c.405delC
  • NM_181798.2:c.1512delC
  • NP_000209.2:p.Arg632Glufs
  • NP_000209.2:p.Arg632fs
  • NP_000209.2:p.Arg632fs
  • NP_001393765.1:p.Arg600Glufs
  • NP_001393766.1:p.Arg542Glufs
  • NP_001393767.1:p.Arg452Glufs
  • NP_001393768.1:p.Arg136Glufs
  • NP_861463.1:p.Arg505Glufs
  • NP_861463.1:p.Arg505fs
  • LRG_287t1:c.1893del
  • LRG_287t2:c.1512del
  • LRG_287:g.407875del
  • LRG_287p1:p.Arg632fs
  • LRG_287p2:p.Arg505fs
  • NC_000011.9:g.2869089del
  • NC_000011.9:g.2869095del
  • NM_000218.2:c.1893del
  • NM_000218.2:c.1893delC
  • NM_181798.1:c.1512del
  • NR_040711.2:n.1786delC
Protein change:
R505fs
Links:
dbSNP: rs397508104
NCBI 1000 Genomes Browser:
rs397508104
Molecular consequence:
  • NM_000218.3:c.1893del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406836.1:c.1797delC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406837.1:c.1623delC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406838.1:c.1353delC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406839.1:c.405delC - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181798.2:c.1512delC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001355370Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 29, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

Disease characterization using LQTS-specific induced pluripotent stem cells.

Egashira T, Yuasa S, Suzuki T, Aizawa Y, Yamakawa H, Matsuhashi T, Ohno Y, Tohyama S, Okata S, Seki T, Kuroda Y, Yae K, Hashimoto H, Tanaka T, Hattori F, Sato T, Miyoshi S, Takatsuki S, Murata M, Kurokawa J, Furukawa T, Makita N, et al.

Cardiovasc Res. 2012 Sep 1;95(4):419-29. doi: 10.1093/cvr/cvs206. Epub 2012 Jun 27.

PubMed [citation]
PMID:
22739119
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001355370.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant deletes a single nucleotide in the last exon 16 of the KCNQ1 gene, creating a frameshift at codon 632 followed by addition of 33 new amino acids and a stop codon. As a result, this variant alters the cytoplasmic C-terminal region of the KCNQ1 protein. An experimental functional study has shown that in transfected cells, the mutant protein carrying this variant has a dominant-negative effect on the channel function due to a trafficking deficiency (PMID: 22739119). This variant has been reported in 2 or more individuals affected with long QT syndrome (PMID: 16414944, 22739119). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on available evidence, this variant is classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024