NM_000238.4(KCNH2):c.1205A>G (p.His402Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 10, 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:: RCV002460903.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.1205A>G (p.His402Arg)]

NM_000238.4(KCNH2):c.1205A>G (p.His402Arg)

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.1205A>G (p.His402Arg)

HGVS:

NC_000007.14:g.150952777T>C
NG_008916.1:g.30150A>G
NM_000238.4:c.1205A>GMANE SELECT
NM_001204798.2:c.185A>G
NM_001406753.1:c.917A>G
NM_001406755.1:c.1028A>G
NM_001406756.1:c.917A>G
NM_001406757.1:c.905A>G
NM_172056.3:c.1205A>G
NM_172057.3:c.185A>G
NP_000229.1:p.His402Arg
NP_000229.1:p.His402Arg
NP_001191727.1:p.His62Arg
NP_001393682.1:p.His306Arg
NP_001393684.1:p.His343Arg
NP_001393685.1:p.His306Arg
NP_001393686.1:p.His302Arg
NP_742053.1:p.His402Arg
NP_742053.1:p.His402Arg
NP_742054.1:p.His62Arg
NP_742054.1:p.His62Arg
LRG_288t1:c.1205A>G
LRG_288t2:c.1205A>G
LRG_288t3:c.185A>G
LRG_288:g.30150A>G
LRG_288p1:p.His402Arg
LRG_288p2:p.His402Arg
LRG_288p3:p.His62Arg
NC_000007.13:g.150649865T>C
NM_000238.2:c.1205A>G
NM_000238.3:c.1205A>G
NM_172056.2:c.1205A>G
NM_172057.2:c.185A>G
NR_176254.1:n.1613A>G
NR_176255.1:n.486A>G
Q12809:p.His402Arg

Protein change:

H302R

Links:

UniProtKB: Q12809#VAR_074808; dbSNP: rs199473506

NCBI 1000 Genomes Browser:

rs199473506

Molecular consequence:

NM_000238.4:c.1205A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.185A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.917A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1028A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.917A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.905A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1205A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.185A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002756997	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002756997

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV002756997.1

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

Description

Published functional studies demonstrate a damaging effect; specifically in vitro analyses demonstrated reduced membrane channel expression and significantly altered gating properties of the expressed channel that resulted in altered physiological phenotypes associated with H402R-hERG relative to WT-hERG (PMID: 28280240); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23631430, 19716085, 21185501, 19136169, 22581653, 26669661, 28280240)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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