NM_000238.4(KCNH2):c.1352C>T (p.Pro451Leu) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 2023
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:: RCV001841698.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.1352C>T (p.Pro451Leu)]

NM_000238.4(KCNH2):c.1352C>T (p.Pro451Leu)

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.1352C>T (p.Pro451Leu)

HGVS:

NC_000007.14:g.150952630G>A
NG_008916.1:g.30297C>T
NM_000238.4:c.1352C>TMANE SELECT
NM_001204798.2:c.332C>T
NM_001406753.1:c.1064C>T
NM_001406755.1:c.1175C>T
NM_001406756.1:c.1064C>T
NM_001406757.1:c.1052C>T
NM_172056.3:c.1352C>T
NM_172057.3:c.332C>T
NP_000229.1:p.Pro451Leu
NP_000229.1:p.Pro451Leu
NP_001191727.1:p.Pro111Leu
NP_001393682.1:p.Pro355Leu
NP_001393684.1:p.Pro392Leu
NP_001393685.1:p.Pro355Leu
NP_001393686.1:p.Pro351Leu
NP_742053.1:p.Pro451Leu
NP_742053.1:p.Pro451Leu
NP_742054.1:p.Pro111Leu
NP_742054.1:p.Pro111Leu
LRG_288t1:c.1352C>T
LRG_288t2:c.1352C>T
LRG_288t3:c.332C>T
LRG_288:g.30297C>T
LRG_288p1:p.Pro451Leu
LRG_288p2:p.Pro451Leu
LRG_288p3:p.Pro111Leu
NC_000007.13:g.150649718G>A
NM_000238.3:c.1352C>T
NM_172056.2:c.1352C>T
NM_172057.2:c.332C>T
NR_176254.1:n.1760C>T
NR_176255.1:n.633C>T
Q12809:p.Pro451Leu

Protein change:

P111L

Links:

UniProtKB: Q12809#VAR_014373; dbSNP: rs199472902

NCBI 1000 Genomes Browser:

rs199472902

Molecular consequence:

NM_000238.4:c.1352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1064C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1175C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1064C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1052C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002053078	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10862094, 15541256, 15733182, 29622001, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002053078

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 7, 2023)

germline

clinical testing

PubMed (5)
[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

Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects.

Laitinen P, Fodstad H, Piippo K, Swan H, Toivonen L, Viitasalo M, Kaprio J, Kontula K.

Hum Mutat. 2000 Jun;15(6):580-1.

PubMed [citation]

PMID:: 10862094

Temporal repolarization lability differences among genotyped patients with the long QT syndrome.

Bilchick K, Viitasalo M, Oikarinen L, Fetics B, Tomaselli G, Swan H, Laitinen PJ, Väänänen H, Kontula K, Berger RD.

Am J Cardiol. 2004 Nov 15;94(10):1312-6.

PubMed [citation]

PMID:: 15541256

See all PubMed Citations (5)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV002053078.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense variant replaces proline with leucine at codon 451 of the KCNH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with long QT syndrome (PMID: 10862094, 15541256, 15733182). This variant has also been reported in one individual affected with aborted cardiac arrest (PMID: 29622001). This variant has been identified in 6/251330 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Nov 10, 2024

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