NM_000238.4(KCNH2):c.2135A>G (p.Asp712Gly) AND Long QT syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 4, 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:: RCV002042391.6

Allele description

NM_000238.4(KCNH2):c.2135A>G (p.Asp712Gly)

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.2135A>G (p.Asp712Gly)

HGVS:

NC_000007.14:g.150950931T>C
NG_008916.1:g.31996A>G
NM_000238.4:c.2135A>GMANE SELECT
NM_001204798.2:c.1115A>G
NM_001406753.1:c.1847A>G
NM_001406755.1:c.1958A>G
NM_001406756.1:c.1847A>G
NM_001406757.1:c.1835A>G
NM_172056.3:c.2135A>G
NM_172057.3:c.1115A>G
NP_000229.1:p.Asp712Gly
NP_000229.1:p.Asp712Gly
NP_001191727.1:p.Asp372Gly
NP_001393682.1:p.Asp616Gly
NP_001393684.1:p.Asp653Gly
NP_001393685.1:p.Asp616Gly
NP_001393686.1:p.Asp612Gly
NP_742053.1:p.Asp712Gly
NP_742053.1:p.Asp712Gly
NP_742054.1:p.Asp372Gly
NP_742054.1:p.Asp372Gly
LRG_288t1:c.2135A>G
LRG_288t2:c.2135A>G
LRG_288t3:c.1115A>G
LRG_288:g.31996A>G
LRG_288p1:p.Asp712Gly
LRG_288p2:p.Asp712Gly
LRG_288p3:p.Asp372Gly
NC_000007.13:g.150648019T>C
NM_000238.3:c.2135A>G
NM_172056.2:c.2135A>G
NM_172057.2:c.1115A>G
NR_176254.1:n.2543A>G
NR_176255.1:n.1416A>G

Protein change:

D372G

Links:

dbSNP: rs2116954162

NCBI 1000 Genomes Browser:

rs2116954162

Molecular consequence:

NM_000238.4:c.2135A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.1115A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1847A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1958A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1847A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1835A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.2135A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.1115A>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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AA986695 expressed sequence AA986695 [Mus musculus]
AA986695 expressed sequence AA986695 [Mus musculus]
Gene ID:98247

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002294165	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002294165

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 4, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Invitae, SCV002294165.3

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

Description

This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 712 of the KCNH2 protein (p.Asp712Gly). ClinVar contains an entry for this variant (Variation ID: 1499635). 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. 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.

#	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: Mar 5, 2024

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