NM_000238.4(KCNH2):c.2680_2686del (p.Arg894fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2017
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:: RCV000620946.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.2680_2686del (p.Arg894fs)]

NM_000238.4(KCNH2):c.2680_2686del (p.Arg894fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.2680_2686del (p.Arg894fs)

HGVS:

NC_000007.14:g.150948452_150948458del
NG_008916.1:g.34471_34477del
NM_000238.4:c.2680_2686delMANE SELECT
NM_172057.3:c.1660_1666del
NP_000229.1:p.Arg894fs
NP_742054.1:p.Arg554fs
LRG_288:g.34471_34477del
NC_000007.13:g.150645540_150645546del
NM_000238.3:c.2680_2686delCGCACGG

Protein change:

R554fs

Links:

dbSNP: rs1554424620

NCBI 1000 Genomes Browser:

rs1554424620

Molecular consequence:

NM_000238.4:c.2680_2686del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.1660_1666del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000737869	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 25, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16414944, 19862833 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000737869

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 25, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]

PMID:: 16414944

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

Details of each submission

From Ambry Genetics, SCV000737869.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.2680_2686delCGCACGG pathogenic mutation, located in coding exon 11 of the KCNH2 gene, results from a deletion of 7 nucleotides at nucleotide positions 2680 to 2686, causing a translational frameshift with a predicted alternate stop codon (p.R894Tfs*78). Translational frameshift alterations in this region have been reported in patients with long QT syndrome (Napolitano C et al. JAMA, 2005 Dec;294:2975-80; Hedley PL et al. Hum. Mutat., 2009 Nov;30:1486-511). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 1, 2024

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