NM_000218.3(KCNQ1):c.1354del (p.Arg452fs) AND Cardiac arrhythmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 20, 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:: RCV003591903.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1354del (p.Arg452fs)]

NM_000218.3(KCNQ1):c.1354del (p.Arg452fs)

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.1354del (p.Arg452fs)

HGVS:

NC_000011.10:g.2588815del
NG_008935.1:g.148825del
NM_000218.3:c.1354delMANE SELECT
NM_001406836.1:c.1258delC
NM_001406837.1:c.1084delC
NM_001406838.1:c.814delC
NM_181798.2:c.973delC
NP_000209.2:p.Arg452Glyfs
NP_000209.2:p.Arg452fs
NP_001393765.1:p.Arg420Glyfs
NP_001393766.1:p.Arg362Glyfs
NP_001393767.1:p.Arg272Glyfs
NP_861463.1:p.Arg325Glyfs
NP_861463.1:p.Arg325fs
LRG_287t1:c.1354del
LRG_287t2:c.973del
LRG_287:g.148825del
LRG_287p1:p.Arg452Glyfs
LRG_287p2:p.Arg325fs
NC_000011.9:g.2610045del
NM_000218.2:c.1354delC
NM_181798.1:c.973del
NR_040711.2:n.1247delC

Protein change:

R325fs

Links:

dbSNP: rs2133760795

NCBI 1000 Genomes Browser:

rs2133760795

Molecular consequence:

NM_000218.3:c.1354del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.1258delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.1084delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406838.1:c.814delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.973delC - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004358420	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004358420

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 20, 2023)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004358420.1

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

Description

This variant deletes 1 nucleotide in exon 10 of the KCNQ1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with KCNQ1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of KCNQ1 function is a known mechanism of disease (clinicalgenome.org). 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 29, 2024

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