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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:
RCV003531955.2

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004294719Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 27, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004294719.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024