NM_000238.4(KCNH2):c.3007dup (p.Asp1003fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 25, 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:: RCV001071824.7

Allele description [Variation Report for NM_000238.4(KCNH2):c.3007dup (p.Asp1003fs)]

NM_000238.4(KCNH2):c.3007dup (p.Asp1003fs)

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.3007dup (p.Asp1003fs)

HGVS:

NC_000007.14:g.150947478dup
NG_008916.1:g.35454dup
NM_000238.4:c.3007dupMANE SELECT
NM_172057.3:c.1987dup
NP_000229.1:p.Asp1003fs
NP_742054.1:p.Asp663fs
LRG_288t1:c.3007dup
LRG_288:g.35454dup
NC_000007.13:g.150644560_150644561insC
NC_000007.13:g.150644566dup
NM_000238.3:c.3007dup

Protein change:

D1003fs

Links:

dbSNP: rs1800946921

NCBI 1000 Genomes Browser:

rs1800946921

Molecular consequence:

NM_000238.4:c.3007dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.1987dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001237150	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27920829, 26688388, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001237150

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 25, 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

Clinical and genetic features of Australian families with long QT syndrome: A registry-based study.

Burns C, Ingles J, Davis AM, Connell V, Gray B, Hunt L, McGaughran J, Semsarian C.

J Arrhythm. 2016 Dec;32(6):456-461. Epub 2016 Mar 15.

PubMed [citation]

PMID:: 27920829
PMCID:: PMC5129121

A fast and cost-effective molecular diagnostic tool for genetic diseases involved in sudden cardiac death.

Chanavat V, Janin A, Millat G.

Clin Chim Acta. 2016 Jan 30;453:80-5. doi: 10.1016/j.cca.2015.12.011. Epub 2015 Dec 10.

PubMed [citation]

PMID:: 26688388

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001237150.5

#	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. This variant disrupts a region of the KCNH2 protein in which other variant(s) (p.Glu1119*) have been determined to be pathogenic (PMID: 27920829). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Asp1003Glyfs*116) in the KCNH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 157 amino acid(s) of the KCNH2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KCNH2-related disease (PMID: 26688388). ClinVar contains an entry for this variant (Variation ID: 864600).

#	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

ClinVar

Relating variation to medicine