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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000196764	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 20683999, 25420144

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000196764

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2015)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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