NM_000218.3(KCNQ1):c.1124_1127del (p.Ile375fs) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000182278.12

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1124_1127del (p.Ile375fs)]

NM_000218.3(KCNQ1):c.1124_1127del (p.Ile375fs)

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.1124_1127del (p.Ile375fs)

HGVS:

NC_000011.10:g.2585303_2585306del
NG_008935.1:g.145313_145316del
NM_000218.3:c.1124_1127delMANE SELECT
NM_001406837.1:c.854_857delTTCA
NM_181798.2:c.743_746delTTCA
NP_000209.2:p.Ile375Argfs
NP_000209.2:p.Ile375fs
NP_000209.2:p.Ile375fs
NP_001393766.1:p.Ile285Argfs
NP_861463.1:p.Ile248Argfs
NP_861463.1:p.Ile248fs
LRG_287t1:c.1124_1127del
LRG_287t2:c.743_746del
LRG_287:g.145313_145316del
LRG_287p1:p.Ile375fs
LRG_287p2:p.Ile248fs
NC_000011.9:g.2606530_2606533del
NC_000011.9:g.2606533_2606536del
NM_000218.2:c.1124_1127del
NM_000218.2:c.1124_1127delTTCA
NM_181798.1:c.743_746del
NM_181798.1:c.743_746delTTCA
NR_040711.2:n.1017_1020delTTCA
p.I375RfsX43

Protein change:

I248fs

Links:

dbSNP: rs397508077

NCBI 1000 Genomes Browser:

rs397508077

Molecular consequence:

NM_000218.3:c.1124_1127del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.854_857delTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.743_746delTTCA - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234581	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 11, 2023)	germline	clinical testing	Citation Link,
SCV001923993	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001954057	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002502325	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15840476, 28532774, 30291343, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]

PMID:: 15840476

Genotype Positive Long QT Syndrome in Patients With Coexisting Congenital Heart Disease.

Ebrahim MA, Williams MR, Shepard S, Perry JC.

Am J Cardiol. 2017 Jul 15;120(2):256-261. doi: 10.1016/j.amjcard.2017.04.018. Epub 2017 Apr 27.

PubMed [citation]

PMID:: 28532774

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000234581.16

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28532774, 30291343, 26669661, 15840476)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001923993.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001954057.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From AiLife Diagnostics, AiLife Diagnostics, SCV002502325.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 1, 2024

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