NM_000238.4(KCNH2):c.2762del (p.Gly921fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 19, 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:: RCV002440737.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.2762del (p.Gly921fs)]

NM_000238.4(KCNH2):c.2762del (p.Gly921fs)

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.2762del (p.Gly921fs)

HGVS:

NC_000007.14:g.150947812del
NG_008916.1:g.35118del
NM_000238.4:c.2762delMANE SELECT
NM_172057.3:c.1742del
NP_000229.1:p.Gly921fs
NP_742054.1:p.Gly581fs
LRG_288t1:c.2762del
LRG_288:g.35118del
NC_000007.13:g.150644897del
NC_000007.13:g.150644900del
NM_000238.2:c.2762delG
NM_000238.3:c.2762del
NM_000238.3:c.2762delG

Protein change:

G581fs

Links:

dbSNP: rs1584845263

NCBI 1000 Genomes Browser:

rs1584845263

Molecular consequence:

NM_000238.4:c.2762del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.1742del - 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
SCV002752036	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10973849, 15840476 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002752036

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 19, 2022)

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

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

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Tester DJ, Will ML, Haglund CM, Ackerman MJ.

Heart Rhythm. 2005 May;2(5):507-17.

PubMed [citation]

PMID:: 15840476

Details of each submission

From Ambry Genetics, SCV002752036.2

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

Description

The c.2762delG pathogenic mutation, located in coding exon 12 of the KCNH2 gene, results from a deletion of one nucleotide at nucleotide position 2762, causing a translational frameshift with a predicted alternate stop codon (p.G921Afs*53). This variant (also described as p.R920fs*51) has been reported in individuals with long QT syndrome, although clinical details were limited (Splawski I et al. Circulation, 2000 Sep;102:1178-85; Tester DJ et al. Heart Rhythm, 2005 May;2:507-17). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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: Sep 29, 2024

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