U.S. flag

An official website of the United States government

NM_000238.4(KCNH2):c.1881C>A (p.Phe627Leu) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 16, 2011
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:
RCV000182034.2

Allele description [Variation Report for NM_000238.4(KCNH2):c.1881C>A (p.Phe627Leu)]

NM_000238.4(KCNH2):c.1881C>A (p.Phe627Leu)

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.1881C>A (p.Phe627Leu)
Other names:
p.F627L:TTC>TTA
HGVS:
  • NC_000007.14:g.150951512G>T
  • NG_008916.1:g.31415C>A
  • NM_000238.4:c.1881C>AMANE SELECT
  • NM_001204798.2:c.861C>A
  • NM_001406753.1:c.1593C>A
  • NM_001406755.1:c.1704C>A
  • NM_001406756.1:c.1593C>A
  • NM_001406757.1:c.1581C>A
  • NM_172056.3:c.1881C>A
  • NM_172057.3:c.861C>A
  • NP_000229.1:p.Phe627Leu
  • NP_000229.1:p.Phe627Leu
  • NP_001191727.1:p.Phe287Leu
  • NP_001393682.1:p.Phe531Leu
  • NP_001393684.1:p.Phe568Leu
  • NP_001393685.1:p.Phe531Leu
  • NP_001393686.1:p.Phe527Leu
  • NP_742053.1:p.Phe627Leu
  • NP_742053.1:p.Phe627Leu
  • NP_742054.1:p.Phe287Leu
  • NP_742054.1:p.Phe287Leu
  • LRG_288t1:c.1881C>A
  • LRG_288t2:c.1881C>A
  • LRG_288t3:c.861C>A
  • LRG_288:g.31415C>A
  • LRG_288p1:p.Phe627Leu
  • LRG_288p2:p.Phe627Leu
  • LRG_288p3:p.Phe287Leu
  • NC_000007.13:g.150648600G>T
  • NM_000238.2:c.1881C>A
  • NM_000238.3:c.1881C>A
  • NM_172056.2:c.1881C>A
  • NM_172057.2:c.861C>A
  • NR_176254.1:n.2289C>A
  • NR_176255.1:n.1162C>A
  • Q12809:p.Phe627Leu
Protein change:
F287L
Links:
UniProtKB: Q12809#VAR_014377; dbSNP: rs199473039
NCBI 1000 Genomes Browser:
rs199473039
Molecular consequence:
  • NM_000238.4:c.1881C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.861C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406753.1:c.1593C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406755.1:c.1704C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406756.1:c.1593C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406757.1:c.1581C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.3:c.1881C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.861C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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
SCV000234337GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Sep 16, 2011) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000234337.9

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

Description

The Phe627Leu mutation in the KCNH2 gene has been published previously in association with LQTS (1-3). Phe627Leu, located in the pore region of the protein, has been reported in individuals with LQTS who harbored a different nucleotide substitution which resulted in the same Phe627Leu protein change as this patient (c.1879 T>C and c.1881 C>G, respectively). Lin et al. (2008) reported a 25-week fetus with intermittent AV block due to an extremely long QT interval who harbored the Phe627Leu mutation in the KCNH2 gene, as well as a missense mutation in the SCN5A gene. Another mutation affecting the same residue (Phe627Ile) as well as neighboring residues (Val625Glu, Gly626Ala, Gly626Asp, Gly626Ser, Gly626Val, Gly628Ala, Gly628Ser, Gly628Val) have also been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. Phe627Leu was not detected in over 400 control chromosomes reported in the literature, nor in up to 400 control chromosomes of African American and Caucasian ancestry tested at GeneDx, indicating it is not a common benign polymorphism in these populations. Therefore, the presence of the Phe627Leu mutation in the KCNH2 gene is consistent with a diagnosis of an autosomal dominant form of LQTS. The variant is found in LQT panel(s).

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

Last Updated: Sep 29, 2024