NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jul 23, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000181824.1

Allele description [Variation Report for NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser)]

NM_000238.4(KCNH2):c.1894C>T (p.Pro632Ser)

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.1894C>T (p.Pro632Ser)
Other names:
p.P632S:CCC>TCC
HGVS:
  • NC_000007.14:g.150951499G>A
  • NG_008916.1:g.31428C>T
  • NM_000238.4:c.1894C>TMANE SELECT
  • NM_001204798.2:c.874C>T
  • NM_172056.2:c.1894C>T
  • NM_172057.3:c.874C>T
  • NP_000229.1:p.Pro632Ser
  • NP_000229.1:p.Pro632Ser
  • NP_001191727.1:p.Pro292Ser
  • NP_742053.1:p.Pro632Ser
  • NP_742054.1:p.Pro292Ser
  • LRG_288t1:c.1894C>T
  • LRG_288t2:c.1894C>T
  • LRG_288:g.31428C>T
  • LRG_288p1:p.Pro632Ser
  • LRG_288p2:p.Pro632Ser
  • NC_000007.13:g.150648587G>A
  • NM_000238.2:c.1894C>T
  • NM_000238.3:c.1894C>T
  • Q12809:p.Pro632Ser
Protein change:
P292S
Links:
UniProtKB: Q12809#VAR_014378; dbSNP: rs199473527
NCBI 1000 Genomes Browser:
rs199473527
Molecular consequence:
  • NM_000238.4:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.874C>T - 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
SCV000234127GeneDxcriteria provided, single submitter
Pathogenic
(Jul 23, 2014)
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, SCV000234127.9

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

Description

p.Pro632Ser (CCC>TCC): c.1894 C>T in exon 7 of the KCNH2 gene (NM_000238.2). The P632S mutation in the KCNH2 gene has been reported in one individual with LQTS and it was absent from more than 400 control chromosomes (Splawski I et al., 2000). Furthermore, the P632S mutation 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 addition, P632S results in a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties, at a position that is conserved across mammalian species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Moreover, a mutation in this residue (P632A) and mutations in nearby residues (S631A, N633D, N633I, N633S, N633K) have been reported in association with LQTS, further supporting the functional importance of this residue andregion of the protein. In summary, P632S in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).

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

Last Updated: Dec 4, 2021

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