NM_000238.4(KCNH2):c.1128+1792C>T AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2016
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:: RCV000475454.7

Allele description [Variation Report for NM_000238.4(KCNH2):c.1128+1792C>T]

NM_000238.4(KCNH2):c.1128+1792C>T

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.1128+1792C>T

HGVS:

NC_000007.14:g.150955499G>A
NG_008916.1:g.27428C>T
NM_000238.4:c.1128+1792C>TMANE SELECT
NM_001204798.2:c.5C>T
NM_001406753.1:c.840+1792C>T
NM_001406755.1:c.951+1792C>T
NM_001406756.1:c.840+1792C>T
NM_001406757.1:c.828+1792C>T
NM_172056.3:c.1128+1792C>T
NM_172057.3:c.5C>T
NP_001191727.1:p.Ala2Val
NP_742054.1:p.Ala2Val
NP_742054.1:p.Ala2Val
LRG_288t3:c.5C>T
LRG_288:g.27428C>T
LRG_288p3:p.Ala2Val
NC_000007.13:g.150652587G>A
NM_172057.2:c.5C>T
NR_176255.1:n.306C>T

Protein change:

A2V

Links:

dbSNP: rs1060500667

NCBI 1000 Genomes Browser:

rs1060500667

Molecular consequence:

NM_000238.4:c.1128+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001406753.1:c.840+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001406755.1:c.951+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001406756.1:c.840+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001406757.1:c.828+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_172056.3:c.1128+1792C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001204798.2:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_176255.1:n.306C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

Recent activity

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Fam170a family with sequence similarity 170, member A [Mus musculus]
Fam170a family with sequence similarity 170, member A [Mus musculus]
Gene ID:225497

Gene
225497[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000543438	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2016)	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

SCV000543438

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2016)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000543438.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNH2-related disease. This sequence change replaces alanine with valine at codon 2 of the KCNH2 protein (p.Ala2Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. The KCNH2 gene has multiple clinically relevant isoforms. The p.Ala2Val variant occurs in alternate transcript NM_172057.2, which corresponds to position c.1128+1792C>T in NM_000238.3, the primary transcript listed in the Methods.

#	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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