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NM_000238.4(KCNH2):c.1979C>T (p.Ser660Leu) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 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:
RCV000621327.5

Allele description [Variation Report for NM_000238.4(KCNH2):c.1979C>T (p.Ser660Leu)]

NM_000238.4(KCNH2):c.1979C>T (p.Ser660Leu)

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.1979C>T (p.Ser660Leu)
Other names:
p.S660L:TCG>TTG
HGVS:
  • NC_000007.14:g.150951087G>A
  • NG_008916.1:g.31840C>T
  • NM_000238.4:c.1979C>TMANE SELECT
  • NM_001204798.2:c.959C>T
  • NM_001406753.1:c.1691C>T
  • NM_001406755.1:c.1802C>T
  • NM_001406756.1:c.1691C>T
  • NM_001406757.1:c.1679C>T
  • NM_172056.3:c.1979C>T
  • NM_172057.3:c.959C>T
  • NP_000229.1:p.Ser660Leu
  • NP_000229.1:p.Ser660Leu
  • NP_001191727.1:p.Ser320Leu
  • NP_001393682.1:p.Ser564Leu
  • NP_001393684.1:p.Ser601Leu
  • NP_001393685.1:p.Ser564Leu
  • NP_001393686.1:p.Ser560Leu
  • NP_742053.1:p.Ser660Leu
  • NP_742053.1:p.Ser660Leu
  • NP_742054.1:p.Ser320Leu
  • NP_742054.1:p.Ser320Leu
  • LRG_288t1:c.1979C>T
  • LRG_288t2:c.1979C>T
  • LRG_288t3:c.959C>T
  • LRG_288:g.31840C>T
  • LRG_288p1:p.Ser660Leu
  • LRG_288p2:p.Ser660Leu
  • LRG_288p3:p.Ser320Leu
  • NC_000007.13:g.150648175G>A
  • NM_000238.2:c.1979C>T
  • NM_000238.3:c.1979C>T
  • NM_172056.2:c.1979C>T
  • NM_172057.2:c.959C>T
  • NR_176254.1:n.2387C>T
  • NR_176255.1:n.1260C>T
  • Q12809:p.Ser660Leu
Protein change:
S320L
Links:
UniProtKB: Q12809#VAR_074865; dbSNP: rs199472979
NCBI 1000 Genomes Browser:
rs199472979
Molecular consequence:
  • NM_000238.4:c.1979C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.959C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.1691C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.1802C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.1691C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.1679C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.1979C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.959C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000737497Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 1, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

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
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000737497.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.S660L pathogenic mutation (also known as c.1979C>T), located in coding exon 8 of the KCNH2 gene, results from a C to T substitution at nucleotide position 1979. The serine at codon 660 is replaced by leucine, an amino acid with dissimilar properties. This mutation was reported in several individuals with long QT syndrome (LQTS) (Napolitano C et al. JAMA. 2005;294(23):2975-80). Additionally, this mutation was described as likely de novo in a sporadic case of LQTS and observed to segregate with disease in multiple individuals in two other families (Napolitano C, personal communication). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Jun 9, 2024