NM_000238.4(KCNH2):c.2387T>G (p.Val796Gly) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 25, 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:: RCV003532196.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.2387T>G (p.Val796Gly)]

NM_000238.4(KCNH2):c.2387T>G (p.Val796Gly)

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.2387T>G (p.Val796Gly)

HGVS:

NC_000007.14:g.150950179A>C
NG_008916.1:g.32748T>G
NM_000238.4:c.2387T>GMANE SELECT
NM_001204798.2:c.1367T>G
NM_001406753.1:c.2099T>G
NM_001406755.1:c.2210T>G
NM_001406756.1:c.2099T>G
NM_001406757.1:c.2087T>G
NM_172056.3:c.2387T>G
NM_172057.3:c.1367T>G
NP_000229.1:p.Val796Gly
NP_000229.1:p.Val796Gly
NP_001191727.1:p.Val456Gly
NP_001393682.1:p.Val700Gly
NP_001393684.1:p.Val737Gly
NP_001393685.1:p.Val700Gly
NP_001393686.1:p.Val696Gly
NP_742053.1:p.Val796Gly
NP_742053.1:p.Val796Gly
NP_742054.1:p.Val456Gly
NP_742054.1:p.Val456Gly
LRG_288t1:c.2387T>G
LRG_288t2:c.2387T>G
LRG_288t3:c.1367T>G
LRG_288:g.32748T>G
LRG_288p1:p.Val796Gly
LRG_288p2:p.Val796Gly
LRG_288p3:p.Val456Gly
NC_000007.13:g.150647267A>C
NM_000238.3:c.2387T>G
NM_172056.2:c.2387T>G
NM_172057.2:c.1367T>G
NR_176254.1:n.2795T>G
NR_176255.1:n.1668T>G

Protein change:

V456G

Links:

dbSNP: rs1554425163

NCBI 1000 Genomes Browser:

rs1554425163

Molecular consequence:

NM_000238.4:c.2387T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.1367T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.2099T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.2210T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.2099T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.2087T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.2387T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1367T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004310196	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25294783, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004310196

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 25, 2023)

germline

clinical testing

PubMed (2)
[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

Electrophysiologic substrate in congenital Long QT syndrome: noninvasive mapping with electrocardiographic imaging (ECGI).

Vijayakumar R, Silva JNA, Desouza KA, Abraham RL, Strom M, Sacher F, Van Hare GF, Haïssaguerre M, Roden DM, Rudy Y.

Circulation. 2014 Nov 25;130(22):1936-1943. doi: 10.1161/CIRCULATIONAHA.114.011359. Epub 2014 Oct 7.

PubMed [citation]

PMID:: 25294783
PMCID:: PMC4245321

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004310196.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 518748). This missense change has been observed in individual(s) with long QT syndrome (PMID: 25294783). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 796 of the KCNH2 protein (p.Val796Gly).

#	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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