U.S. flag

An official website of the United States government

NM_000238.4(KCNH2):c.1293C>A (p.Phe431Leu) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 28, 2021
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:
RCV002381372.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.1293C>A (p.Phe431Leu)]

NM_000238.4(KCNH2):c.1293C>A (p.Phe431Leu)

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.1293C>A (p.Phe431Leu)
HGVS:
  • NC_000007.14:g.150952689G>T
  • NG_008916.1:g.30238C>A
  • NM_000238.4:c.1293C>AMANE SELECT
  • NM_001204798.2:c.273C>A
  • NM_001406753.1:c.1005C>A
  • NM_001406755.1:c.1116C>A
  • NM_001406756.1:c.1005C>A
  • NM_001406757.1:c.993C>A
  • NM_172056.3:c.1293C>A
  • NM_172057.3:c.273C>A
  • NP_000229.1:p.Phe431Leu
  • NP_000229.1:p.Phe431Leu
  • NP_001191727.1:p.Phe91Leu
  • NP_001393682.1:p.Phe335Leu
  • NP_001393684.1:p.Phe372Leu
  • NP_001393685.1:p.Phe335Leu
  • NP_001393686.1:p.Phe331Leu
  • NP_742053.1:p.Phe431Leu
  • NP_742053.1:p.Phe431Leu
  • NP_742054.1:p.Phe91Leu
  • NP_742054.1:p.Phe91Leu
  • LRG_288t1:c.1293C>A
  • LRG_288t2:c.1293C>A
  • LRG_288t3:c.273C>A
  • LRG_288:g.30238C>A
  • LRG_288p1:p.Phe431Leu
  • LRG_288p2:p.Phe431Leu
  • LRG_288p3:p.Phe91Leu
  • NC_000007.13:g.150649777G>T
  • NM_000238.2:c.1293C>A
  • NM_000238.3:c.1293C>A
  • NM_172056.2:c.1293C>A
  • NM_172057.2:c.273C>A
  • NR_176254.1:n.1701C>A
  • NR_176255.1:n.574C>A
  • Q12809:p.Phe431Leu
Protein change:
F331L
Links:
UniProtKB: Q12809#VAR_074814; dbSNP: rs199472900
NCBI 1000 Genomes Browser:
rs199472900
Molecular consequence:
  • NM_000238.4:c.1293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.273C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.1005C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.1116C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.1005C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.993C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.1293C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.273C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002689540Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 28, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002689540.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.F431L pathogenic mutation (also known as c.1293C>A), located in coding exon 6 of the KCNH2 gene, results from a C to A substitution at nucleotide position 1293. The phenylalanine at codon 431 is replaced by leucine, an amino acid with highly similar properties, and is located in the S1/S2 transmembrane-spanning region of the protein. This alteration has been reported in a long QT syndrome genetic testing cohort, as well as in an individual with a clinical diagnosis of long QT syndrome, segregating in multiple affected family members (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; GeneDx pers. comm.). In addition, a different alteration located at the same position, resulting in the same protein change, c.1291T>C (p.F431L), has been reported in an individual with a clinical diagnosis of long QT syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Sep 29, 2024