NM_000218.3(KCNQ1):c.554_575del (p.Val185fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 2022
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:: RCV003019541.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.554_575del (p.Val185fs)]

NM_000218.3(KCNQ1):c.554_575del (p.Val185fs)

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.554_575del (p.Val185fs)

HGVS:

NC_000011.10:g.2570704_2570725del
NG_008935.1:g.130714_130735del
NM_000218.3:c.554_575delMANE SELECT
NM_001406836.1:c.554_575del22
NM_001406837.1:c.284_305del22
NM_181798.2:c.173_194del22
NP_000209.2:p.Val185Alafs
NP_000209.2:p.Val185fs
NP_001393765.1:p.Val185Alafs
NP_001393766.1:p.Val95Alafs
NP_861463.1:p.Val58Alafs
NP_861463.1:p.Val58fs
LRG_287t1:c.554_575del22
LRG_287t2:c.173_194del
LRG_287:g.130714_130735del
LRG_287p1:p.Val185Alafs
LRG_287p2:p.Val58fs
NC_000011.9:g.2591932_2591953del
NC_000011.9:g.2591934_2591955del
NM_000218.2:c.554_575del22
NM_181798.1:c.173_194del
NR_040711.2:n.447_468del22

Protein change:

V185fs

Molecular consequence:

NM_000218.3:c.554_575del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.554_575del22 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.284_305del22 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.173_194del22 - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003321918	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9323054, 19862833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003321918

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 23, 2022)

germline

clinical testing

PubMed (3)
[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

Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.

Shalaby FY, Levesque PC, Yang WP, Little WA, Conder ML, Jenkins-West T, Blanar MA.

Circulation. 1997 Sep 16;96(6):1733-6.

PubMed [citation]

PMID:: 9323054

The genetic basis of long QT and short QT syndromes: a mutation update.

Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M.

Hum Mutat. 2009 Nov;30(11):1486-511. doi: 10.1002/humu.21106. Review.

PubMed [citation]

PMID:: 19862833

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003321918.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val185Alafs*45) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833).

#	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: Feb 20, 2024

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