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NM_172362.3(KCNH1):c.651G>C (p.Lys217Asn) AND Temple-Baraitser syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 1, 2015
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000149913.4

Allele description [Variation Report for NM_172362.3(KCNH1):c.651G>C (p.Lys217Asn)]

NM_172362.3(KCNH1):c.651G>C (p.Lys217Asn)

Gene:
KCNH1:potassium voltage-gated channel subfamily H member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.2
Genomic location:
Preferred name:
NM_172362.3(KCNH1):c.651G>C (p.Lys217Asn)
HGVS:
  • NC_000001.11:g.211019164C>G
  • NG_029777.1:g.119952G>C
  • NG_029777.2:g.119952G>C
  • NM_002238.4:c.651G>C
  • NM_172362.3:c.651G>CMANE SELECT
  • NP_002229.1:p.Lys217Asn
  • NP_758872.1:p.Lys217Asn
  • NC_000001.10:g.211192506C>G
  • NM_172362.2:c.651G>C
  • O95259:p.Lys217Asn
Protein change:
K217N; LYS217ASN
Links:
UniProtKB: O95259#VAR_072612; OMIM: 603305.0004; dbSNP: rs727502822
NCBI 1000 Genomes Browser:
rs727502822
Molecular consequence:
  • NM_002238.4:c.651G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172362.3:c.651G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Temple-Baraitser syndrome (TMBTS)
Synonyms:
Severe mental retardation and absent nails of hallux and pollex
Identifiers:
MONDO: MONDO:0012735; MedGen: C2678486; Orphanet: 420561; OMIM: 611816

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000196764OMIM
no assertion criteria provided
Pathogenic
(Jan 1, 2015) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Temple-Baraitser syndrome: a rare and possibly unrecognized condition.

Jacquinet A, Gérard M, Gabbett MT, Rausin L, Misson JP, Menten B, Mortier G, Van Maldergem L, Verloes A, Debray FG.

Am J Med Genet A. 2010 Sep;152A(9):2322-6. doi: 10.1002/ajmg.a.33574.

PubMed [citation]
PMID:
20683999

Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.

Simons C, Rash LD, Crawford J, Ma L, Cristofori-Armstrong B, Miller D, Ru K, Baillie GJ, Alanay Y, Jacquinet A, Debray FG, Verloes A, Shen J, Yesil G, Guler S, Yuksel A, Cleary JG, Grimmond SM, McGaughran J, King GF, Gabbett MT, Taft RJ.

Nat Genet. 2015 Jan;47(1):73-7. doi: 10.1038/ng.3153. Epub 2014 Nov 24. Erratum in: Nat Genet. 2015 Mar;47(3):304. doi: 10.1038/ng0315-304b.

PubMed [citation]
PMID:
25420144

Details of each submission

From OMIM, SCV000196764.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a girl, born of unrelated Algerian parents, with Temple-Baraitser syndrome (TMBTS; 611816), previously reported by Jacquinet et al. (2010), Simons et al. (2015) identified a de novo heterozygous c.651G-C transversion in exon 6 of the KCNH1 gene, resulting in a lys217-to-asn (K217N) substitution at a highly conserved residue near the boundary between the N-terminal cytoplasmic domain and the S1 transmembrane helix. The mutation, which was found by whole-exome sequencing, was not present in the dbSNP (build 141), 1000 Genomes Project, or Exome Sequencing Project databases, or in an in-house control exome dataset of 100 family trios of children with neurologic disorders. In vitro functional expression studies in Xenopus oocytes showed that the mutation caused a decreased threshold of activation and delayed deactivation compared to wildtype, consistent with a gain of function.

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

Last Updated: Apr 23, 2022