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NM_000238.4(KCNH2):c.1922C>T (p.Ser641Phe) AND Long QT syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 30, 2019
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:
RCV000803218.7

Allele description [Variation Report for NM_000238.4(KCNH2):c.1922C>T (p.Ser641Phe)]

NM_000238.4(KCNH2):c.1922C>T (p.Ser641Phe)

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.1922C>T (p.Ser641Phe)
HGVS:
  • NC_000007.14:g.150951471G>A
  • NG_008916.1:g.31456C>T
  • NM_000238.4:c.1922C>TMANE SELECT
  • NM_001204798.2:c.902C>T
  • NM_001406753.1:c.1634C>T
  • NM_001406755.1:c.1745C>T
  • NM_001406756.1:c.1634C>T
  • NM_001406757.1:c.1622C>T
  • NM_172056.3:c.1922C>T
  • NM_172057.3:c.902C>T
  • NP_000229.1:p.Ser641Phe
  • NP_000229.1:p.Ser641Phe
  • NP_001191727.1:p.Ser301Phe
  • NP_001393682.1:p.Ser545Phe
  • NP_001393684.1:p.Ser582Phe
  • NP_001393685.1:p.Ser545Phe
  • NP_001393686.1:p.Ser541Phe
  • NP_742053.1:p.Ser641Phe
  • NP_742053.1:p.Ser641Phe
  • NP_742054.1:p.Ser301Phe
  • NP_742054.1:p.Ser301Phe
  • LRG_288t1:c.1922C>T
  • LRG_288t2:c.1922C>T
  • LRG_288t3:c.902C>T
  • LRG_288:g.31456C>T
  • LRG_288p1:p.Ser641Phe
  • LRG_288p2:p.Ser641Phe
  • LRG_288p3:p.Ser301Phe
  • NC_000007.13:g.150648559G>A
  • NM_000238.3:c.1922C>T
  • NM_172056.2:c.1922C>T
  • NM_172057.2:c.902C>T
  • NR_176254.1:n.2330C>T
  • NR_176255.1:n.1203C>T
  • Q12809:p.Ser641Phe
Protein change:
S301F
Links:
UniProtKB: Q12809#VAR_068273; dbSNP: rs199472971
NCBI 1000 Genomes Browser:
rs199472971
Molecular consequence:
  • NM_000238.4:c.1922C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.1745C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.1622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.1922C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.902C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000943080Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Apr 30, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome.

Giudicessi JR, Kapplinger JD, Tester DJ, Alders M, Salisbury BA, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2012 Oct 1;5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. Epub 2012 Sep 4.

PubMed [citation]
PMID:
22949429
PMCID:
PMC3705705
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000943080.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect KCNH2 protein function (PMID: 25417810). This variant has been observed to be de novo in an individual affected with long QT syndrome (Invitae), and has been reported in other affected individuals (PMID: 22949429, 18441445, 21769575). ClinVar contains an entry for this variant (Variation ID: 67337). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 641 of the KCNH2 protein (p.Ser641Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine.

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

Last Updated: Sep 29, 2024