NM_000238.4(KCNH2):c.422dup (p.Ala142fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 2021
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:: RCV001975050.7

Allele description [Variation Report for NM_000238.4(KCNH2):c.422dup (p.Ala142fs)]

NM_000238.4(KCNH2):c.422dup (p.Ala142fs)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.422dup (p.Ala142fs)

HGVS:

NC_000007.14:g.150959625dup
NG_008916.1:g.23305dup
NM_000238.4:c.422dupMANE SELECT
NM_001406753.1:c.131dup
NM_001406755.1:c.242dup
NM_001406756.1:c.131dup
NM_001406757.1:c.119dup
NM_172056.3:c.419dup
NP_000229.1:p.Ala142Glyfs
NP_000229.1:p.Ala142fs
NP_001393682.1:p.Ala46Glyfs
NP_001393684.1:p.Ala83Glyfs
NP_001393685.1:p.Ala46Glyfs
NP_001393686.1:p.Ala42Glyfs
NP_742053.1:p.Ala142Glyfs
NP_742053.1:p.Ala142fs
LRG_288t1:c.419dup
LRG_288t2:c.422dup
LRG_288:g.23305dup
LRG_288p1:p.Ala142Glyfs
LRG_288p2:p.Ala142fs
NC_000007.13:g.150656709_150656710insG
NC_000007.13:g.150656713dup
NM_000238.3:c.419dup
NM_000238.3:c.422dupC
NM_172056.2:c.422dup
NR_176254.1:n.827dup

Protein change:

A142fs

Links:

dbSNP: rs2117011733

NCBI 1000 Genomes Browser:

rs2117011733

Molecular consequence:

NM_000238.4:c.422dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406753.1:c.131dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406755.1:c.242dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406756.1:c.131dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406757.1:c.119dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172056.3:c.419dup - 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
SCV002246060	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10973849, 19862833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002246060

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2021)

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

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]

PMID:: 10973849

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002246060.3

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

Description

This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 10973849). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala142Glyfs*3) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 10973849, 19862833). This variant is also known as insC422‚Äì423, P141fs/2. For these reasons, this variant has been 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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