NM_000238.4(KCNH2):c.1886A>C (p.Asn629Thr) AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 10, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000413164.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.1886A>C (p.Asn629Thr)]

NM_000238.4(KCNH2):c.1886A>C (p.Asn629Thr)

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.1886A>C (p.Asn629Thr)
HGVS:
  • NC_000007.14:g.150951507T>G
  • NG_008916.1:g.31420A>C
  • NM_000238.3:c.1886A>C
  • NM_000238.4:c.1886A>CMANE SELECT
  • NM_001204798.2:c.866A>C
  • NM_172056.2:c.1886A>C
  • NM_172057.3:c.866A>C
  • NP_000229.1:p.Asn629Thr
  • NP_000229.1:p.Asn629Thr
  • NP_001191727.1:p.Asn289Thr
  • NP_742053.1:p.Asn629Thr
  • NP_742054.1:p.Asn289Thr
  • LRG_288t1:c.1886A>C
  • LRG_288t2:c.1886A>C
  • LRG_288:g.31420A>C
  • LRG_288p1:p.Asn629Thr
  • LRG_288p2:p.Asn629Thr
  • NC_000007.13:g.150648595T>G
  • NM_000238.2:c.1886A>C
Protein change:
N289T
Links:
dbSNP: rs199472957
NCBI 1000 Genomes Browser:
rs199472957
Molecular consequence:
  • NM_000238.3:c.1886A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000238.4:c.1886A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.866A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1886A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.866A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000490551GeneDxcriteria provided, single submitter
Pathogenic
(Aug 10, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000490551.1

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

Description

The N629T pathogenic variant in the KCNH2 gene has been reported in one individual of European ancestry who was diagnosed with LQTS at the age of 3 years and had a family history of a first degree relative with sudden death before the age of 35 years (Chung S et al., 2007). N629T results in a conservative amino acid substitution at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Moreover, pathogenic variants affecting this same residue, (N629S, N629I, N629K, N629D) and nearby residues (G628R, G628A, G628S, G628V, V630A, V630L) in the highly conserved pore region have been reported in the Human Gene Mutation Database in association with LQTS (Stenson P et al., 2014), further supporting the functional importance of this residue and this region of the protein. Furthermore, N629T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, N629T in the KCNH2 gene is interpreted as a pathogenic variant.

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

Last Updated: Nov 27, 2021

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