NM_000238.4(KCNH2):c.2648_2652dup (p.Arg885fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 24, 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:: RCV003531749.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.2648_2652dup (p.Arg885fs)]

NM_000238.4(KCNH2):c.2648_2652dup (p.Arg885fs)

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.2648_2652dup (p.Arg885fs)

HGVS:

NC_000007.14:g.150948484_150948488dup
NG_008916.1:g.34439_34443dup
NM_000238.4:c.2648_2652dupMANE SELECT
NM_001406753.1:c.2360_2364dup
NM_172057.3:c.1628_1632dup
NP_000229.1:p.Arg885Glyfs
NP_000229.1:p.Arg885fs
NP_001393682.1:p.Arg789fs
NP_742054.1:p.Arg545Glyfs
NP_742054.1:p.Arg545fs
LRG_288t1:c.2648_2652dup
LRG_288t3:c.1628_1632dup
LRG_288:g.34439_34443dup
LRG_288p1:p.Arg885Glyfs
LRG_288p3:p.Arg545Glyfs
NC_000007.13:g.150645571_150645572insTTGCC
NC_000007.13:g.150645572_150645576dup
NM_000238.3:c.2648_2652dup
NM_172057.2:c.1628_1632dup
NR_176254.1:n.3056_3060dup
NR_176255.1:n.1929_1933dup

Protein change:

R545fs

Molecular consequence:

NM_000238.4:c.2648_2652dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406753.1:c.2360_2364dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.1628_1632dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176254.1:n.3056_3060dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176255.1:n.1929_1933dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004314761	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 24, 2023)	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

SCV004314761

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 24, 2023)

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, SCV004314761.1

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

Description

This sequence change creates a premature translational stop signal (p.Arg885Glyfs*91) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. 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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