NM_000238.4(KCNH2):c.1744C>T (p.Arg582Cys) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 10, 2020
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:: RCV000181815.8

Allele description [Variation Report for NM_000238.4(KCNH2):c.1744C>T (p.Arg582Cys)]

NM_000238.4(KCNH2):c.1744C>T (p.Arg582Cys)

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.1744C>T (p.Arg582Cys)

Other names:

p.R582C:CGC>TGC

HGVS:

NC_000007.14:g.150951649G>A
NG_008916.1:g.31278C>T
NM_000238.4:c.1744C>TMANE SELECT
NM_001204798.2:c.724C>T
NM_001406753.1:c.1456C>T
NM_001406755.1:c.1567C>T
NM_001406756.1:c.1456C>T
NM_001406757.1:c.1444C>T
NM_172056.3:c.1744C>T
NM_172057.3:c.724C>T
NP_000229.1:p.Arg582Cys
NP_000229.1:p.Arg582Cys
NP_001191727.1:p.Arg242Cys
NP_001393682.1:p.Arg486Cys
NP_001393684.1:p.Arg523Cys
NP_001393685.1:p.Arg486Cys
NP_001393686.1:p.Arg482Cys
NP_742053.1:p.Arg582Cys
NP_742053.1:p.Arg582Cys
NP_742054.1:p.Arg242Cys
NP_742054.1:p.Arg242Cys
LRG_288t1:c.1744C>T
LRG_288t2:c.1744C>T
LRG_288t3:c.724C>T
LRG_288:g.31278C>T
LRG_288p1:p.Arg582Cys
LRG_288p2:p.Arg582Cys
LRG_288p3:p.Arg242Cys
NC_000007.13:g.150648737G>A
NM_000238.2:c.1744C>T
NM_000238.3:c.1744C>T
NM_172056.2:c.1744C>T
NM_172057.2:c.724C>T
NR_176254.1:n.2152C>T
NR_176255.1:n.1025C>T
Q12809:p.Arg582Cys

Protein change:

R242C; ARG582CYS

Links:

UniProtKB: Q12809#VAR_008581; OMIM: 152427.0009; dbSNP: rs121912508

NCBI 1000 Genomes Browser:

rs121912508

Molecular consequence:

NM_000238.4:c.1744C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1456C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1456C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1444C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1744C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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citrate synthase, mitochondrial precursor [Sus scrofa]
citrate synthase, mitochondrial precursor [Sus scrofa]
gi|47523618|ref|NP_999441.1|

Protein
hypothetical protein SEA_APOCALYPSE_29 [Mycobacterium phage Apocalypse]
hypothetical protein SEA_APOCALYPSE_29 [Mycobacterium phage Apocalypse]
gi|1241129947|gb|ASZ72657.1|

Protein
methyl CpG binding protein 2 [Mus musculus]
methyl CpG binding protein 2 [Mus musculus]
gi|148697898|gb|EDL29845.1||gnl|WGS |mCP10113

Protein
Micromonospora sp. SG15 partial 16S rRNA gene, isolate SG15
Micromonospora sp. SG15 partial 16S rRNA gene, isolate SG15
gi|307343118|emb|FN658661.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234118	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 10, 2020)	germline	clinical testing	Citation Link,
SCV001741590	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001958562	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234118

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 10, 2020)

germline

clinical testing

Citation Link,

SCV001741590

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV001958562

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

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, SCV000234118.8

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

Description

Reported as a potential founder mutation from the Netherlands (Hofman et al., 2011); Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 14428; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect as this variant results in impaired protein trafficking and channel inactivation (Fougere et al., 2011); This variant is associated with the following publications: (PMID: 10220144, 21376840, 15840476, 19716085, 21350584, 17088455, 9973011, 19038855, 12566525, 18441445, 17293393, 22949429, 32686758)

#	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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001741590.3

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

#	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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001958562.1

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

#	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: Jun 9, 2024

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