NM_000238.4(KCNH2):c.1039C>T (p.Pro347Ser) AND Long QT syndrome 2

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: May 28, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000678963.19

Allele description [Variation Report for NM_000238.4(KCNH2):c.1039C>T (p.Pro347Ser)]

NM_000238.4(KCNH2):c.1039C>T (p.Pro347Ser)

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.1039C>T (p.Pro347Ser)

Other names:

p.P347S:CCC>TCC

HGVS:

NC_000007.14:g.150957380G>A
NG_008916.1:g.25547C>T
NM_000238.4:c.1039C>TMANE SELECT
NM_001406753.1:c.751C>T
NM_001406755.1:c.862C>T
NM_001406756.1:c.751C>T
NM_001406757.1:c.739C>T
NM_172056.3:c.1039C>T
NP_000229.1:p.Pro347Ser
NP_000229.1:p.Pro347Ser
NP_001393682.1:p.Pro251Ser
NP_001393684.1:p.Pro288Ser
NP_001393685.1:p.Pro251Ser
NP_001393686.1:p.Pro247Ser
NP_742053.1:p.Pro347Ser
NP_742053.1:p.Pro347Ser
LRG_288t1:c.1039C>T
LRG_288t2:c.1039C>T
LRG_288:g.25547C>T
LRG_288p1:p.Pro347Ser
LRG_288p2:p.Pro347Ser
NC_000007.13:g.150654468G>A
NM_000238.2:c.1039C>T
NM_000238.3:c.1039C>T
NM_172056.2:c.1039C>T
NR_176254.1:n.1447C>T
Q12809:p.Pro347Ser

Protein change:

P247S

Links:

UniProtKB: Q12809#VAR_009912; dbSNP: rs138776684

NCBI 1000 Genomes Browser:

rs138776684

Molecular consequence:

NM_000238.4:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.751C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.862C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.751C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.739C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Long QT syndrome 2 (LQT2)
Identifiers:: MONDO: MONDO:0013367; MedGen: C3150943; Orphanet: 101016; Orphanet: 768; OMIM: 613688

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000805179	Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 17, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001137547	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001324604	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17531263, 20486126, 22378279, 14760488, 10973849, 19673885, 21410720 Citation Link,
SCV001428618	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 21, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A single hERG mutation underlying a spectrum of acquired and congenital long QT syndrome phenotypes.

Saenen JB, Paulussen AD, Jongbloed RJ, Marcelis CL, Gilissen RA, Aerssens J, Snyders DJ, Raes AL.

J Mol Cell Cardiol. 2007 Jul;43(1):63-72. Epub 2007 May 4.

PubMed [citation]

PMID:: 17531263

A new approach to long QT syndrome mutation detection by Sequenom MassARRAY system.

Allegue C, Gil R, Sanchez-Diz P, Torres M, Quintela I, Carracedo A, Brión M.

Electrophoresis. 2010 May;31(10):1648-55. doi: 10.1002/elps.201000022.

PubMed [citation]

PMID:: 20486126

See all PubMed Citations (8)

Details of each submission

From Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues, SCV000805179.1

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

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

From Mendelics, SCV001137547.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001324604.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428618.1

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

#	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		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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