NM_000238.4(KCNH2):c.1813C>T (p.Pro605Ser) AND Long QT syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 27, 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:: RCV003531955.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.1813C>T (p.Pro605Ser)]

NM_000238.4(KCNH2):c.1813C>T (p.Pro605Ser)

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.1813C>T (p.Pro605Ser)

HGVS:

NC_000007.14:g.150951580G>A
NG_008916.1:g.31347C>T
NM_000238.4:c.1813C>TMANE SELECT
NM_001204798.2:c.793C>T
NM_001406753.1:c.1525C>T
NM_001406755.1:c.1636C>T
NM_001406756.1:c.1525C>T
NM_001406757.1:c.1513C>T
NM_172056.3:c.1813C>T
NM_172057.3:c.793C>T
NP_000229.1:p.Pro605Ser
NP_000229.1:p.Pro605Ser
NP_001191727.1:p.Pro265Ser
NP_001393682.1:p.Pro509Ser
NP_001393684.1:p.Pro546Ser
NP_001393685.1:p.Pro509Ser
NP_001393686.1:p.Pro505Ser
NP_742053.1:p.Pro605Ser
NP_742053.1:p.Pro605Ser
NP_742054.1:p.Pro265Ser
NP_742054.1:p.Pro265Ser
LRG_288t1:c.1813C>T
LRG_288t2:c.1813C>T
LRG_288t3:c.793C>T
LRG_288:g.31347C>T
LRG_288p1:p.Pro605Ser
LRG_288p2:p.Pro605Ser
LRG_288p3:p.Pro265Ser
NC_000007.13:g.150648668G>A
NM_000238.3:c.1813C>T
NM_172056.2:c.1813C>T
NM_172057.2:c.793C>T
NR_176254.1:n.2221C>T
NR_176255.1:n.1094C>T
Q12809:p.Pro605Ser

Protein change:

P265S

Links:

UniProtKB: Q12809#VAR_074845; dbSNP: rs199472939

NCBI 1000 Genomes Browser:

rs199472939

Molecular consequence:

NM_000238.4:c.1813C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001204798.2:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406753.1:c.1525C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406756.1:c.1525C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406757.1:c.1513C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.1813C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172057.3:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004294719	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19716085, 25417810, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294719

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 27, 2023)

germline

clinical testing

PubMed (3)
[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

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome.

Anderson CL, Kuzmicki CE, Childs RR, Hintz CJ, Delisle BP, January CT.

Nat Commun. 2014 Nov 24;5:5535. doi: 10.1038/ncomms6535.

PubMed [citation]

PMID:: 25417810
PMCID:: PMC4243539

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004294719.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense change has been observed in individual(s) with clinical features of LQTS (PMID: 19716085; Invitae). In at least one individual the variant was observed to be de novo. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects KCNH2 function (PMID: 25417810). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 67283). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 605 of the KCNH2 protein (p.Pro605Ser).

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine