NM_000238.4(KCNH2):c.1231G>A (p.Asp411Asn) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 27, 2019
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:: RCV001211435.4

Allele description [Variation Report for NM_000238.4(KCNH2):c.1231G>A (p.Asp411Asn)]

NM_000238.4(KCNH2):c.1231G>A (p.Asp411Asn)

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.1231G>A (p.Asp411Asn)

HGVS:

NC_000007.14:g.150952751C>T
NG_008916.1:g.30176G>A
NM_000238.4:c.1231G>AMANE SELECT
NM_001204798.2:c.211G>A
NM_001406753.1:c.943G>A
NM_001406755.1:c.1054G>A
NM_001406756.1:c.943G>A
NM_001406757.1:c.931G>A
NM_172056.3:c.1231G>A
NM_172057.3:c.211G>A
NP_000229.1:p.Asp411Asn
NP_000229.1:p.Asp411Asn
NP_001191727.1:p.Asp71Asn
NP_001393682.1:p.Asp315Asn
NP_001393684.1:p.Asp352Asn
NP_001393685.1:p.Asp315Asn
NP_001393686.1:p.Asp311Asn
NP_742053.1:p.Asp411Asn
NP_742053.1:p.Asp411Asn
NP_742054.1:p.Asp71Asn
NP_742054.1:p.Asp71Asn
LRG_288t1:c.1231G>A
LRG_288t2:c.1231G>A
LRG_288t3:c.211G>A
LRG_288:g.30176G>A
LRG_288p1:p.Asp411Asn
LRG_288p2:p.Asp411Asn
LRG_288p3:p.Asp71Asn
NC_000007.13:g.150649839C>T
NM_000238.3:c.1231G>A
NM_172056.2:c.1231G>A
NM_172057.2:c.211G>A
NR_176254.1:n.1639G>A
NR_176255.1:n.512G>A

Protein change:

D311N

Links:

dbSNP: rs1801230141

NCBI 1000 Genomes Browser:

rs1801230141

Molecular consequence:

NM_000238.4:c.1231G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.943G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1054G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.943G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.931G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1231G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.211G>A - 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
SCV001382976	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29117522, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382976

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2019)

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

The Fast Component of hERG Gating Charge: An Interaction between D411 in the S1 and S4 Residues.

Dou Y, Macdonald LC, Wu Y, Fedida D.

Biophys J. 2017 Nov 7;113(9):1979-1991. doi: 10.1016/j.bpj.2017.09.004.

PubMed [citation]

PMID:: 29117522
PMCID:: PMC5685676

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, SCV001382976.1

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

Description

This sequence change replaces aspartic acid with asparagine at codon 411 of the KCNH2 protein (p.Asp411Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNH2-related conditions. This variant has been reported to affect KCNH2 protein function (PMID: 29117522). 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: Sep 29, 2024

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