NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 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:: RCV001390279.7

Allele description [Variation Report for NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter)]

NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter)

HGVS:

NC_000007.14:g.150958158G>A
NG_008916.1:g.24769C>T
NM_000238.2:c.817C>T
NM_000238.4:c.817C>TMANE SELECT
NM_001406753.1:c.529C>T
NM_001406755.1:c.640C>T
NM_001406756.1:c.529C>T
NM_001406757.1:c.517C>T
NM_172056.3:c.817C>T
NP_000229.1:p.Arg273Ter
NP_000229.1:p.Arg273Ter
NP_001393682.1:p.Arg177Ter
NP_001393684.1:p.Arg214Ter
NP_001393685.1:p.Arg177Ter
NP_001393686.1:p.Arg173Ter
NP_742053.1:p.Arg273Ter
NP_742053.1:p.Arg273Ter
LRG_288t1:c.817C>T
LRG_288t2:c.817C>T
LRG_288:g.24769C>T
LRG_288p1:p.Arg273Ter
LRG_288p2:p.Arg273Ter
NC_000007.13:g.150655246G>A
NM_000238.3:c.817C>T
NM_172056.2:c.817C>T
NR_176254.1:n.1225C>T

Protein change:

R173*

Links:

dbSNP: rs552583527

NCBI 1000 Genomes Browser:

rs552583527

Molecular consequence:

NM_000238.4:c.817C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406753.1:c.529C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406755.1:c.640C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406756.1:c.529C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406757.1:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_172056.3:c.817C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001591957	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10973849, 19862833, 15176425, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591957

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

germline

clinical testing

PubMed (4)
[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 (4)

Details of each submission

From Invitae, SCV001591957.4

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

Description

This sequence change creates a premature translational stop signal (p.Arg273*) 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 premature translational stop signal has been observed in individual(s) with clinical features of KCNH2-related conditions (PMID: 15176425). ClinVar contains an entry for this variant (Variation ID: 1076382). 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: Feb 20, 2024

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