NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs) AND Cardiac arrhythmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 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:: RCV003591905.1

Allele description [Variation Report for NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)]

NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.745_746dup (p.Leu250fs)

HGVS:

NC_000011.10:g.2572074_2572075dup
NG_008935.1:g.132084_132085dup
NM_000218.3:c.745_746dupMANE SELECT
NM_001406836.1:c.745_746dup
NM_001406837.1:c.475_476dup
NM_181798.2:c.364_365dup
NP_000209.2:p.Leu250Glyfs
NP_000209.2:p.Leu250fs
NP_001393765.1:p.Leu250Glyfs
NP_001393766.1:p.Leu160Glyfs
NP_861463.1:p.Leu123Glyfs
NP_861463.1:p.Leu123fs
LRG_287t1:c.745_746dup
LRG_287t2:c.364_365dup
LRG_287:g.132084_132085dup
LRG_287p1:p.Leu250Glyfs
LRG_287p2:p.Leu123fs
NC_000011.9:g.2593302_2593303insGA
NC_000011.9:g.2593304_2593305dup
NM_000218.2:c.745_746dup
NM_181798.1:c.364_365dup
NR_040711.2:n.638_639dup

Protein change:

L123fs

Links:

dbSNP: rs1221462654

NCBI 1000 Genomes Browser:

rs1221462654

Molecular consequence:

NM_000218.3:c.745_746dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.745_746dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.475_476dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.364_365dup - 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
SCV004358387	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 8, 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

SCV004358387

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 8, 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, SCV004358387.1

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

Description

This variant causes duplication of 2 nucleotides in exon 5 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 been identified in 1/248778 chromosomes 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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