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NM_021072.4(HCN1):c.469C>G (p.Leu157Val) AND Generalized epilepsy with febrile seizures plus, type 10

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 25, 2019
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:
RCV000786053.1

Allele description [Variation Report for NM_021072.4(HCN1):c.469C>G (p.Leu157Val)]

NM_021072.4(HCN1):c.469C>G (p.Leu157Val)

Gene:
HCN1:hyperpolarization activated cyclic nucleotide gated potassium channel 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p12
Genomic location:
Preferred name:
NM_021072.4(HCN1):c.469C>G (p.Leu157Val)
HGVS:
  • NC_000005.10:g.45645565G>C
  • NG_042183.1:g.55554C>G
  • NM_021072.4:c.469C>GMANE SELECT
  • NP_066550.2:p.Leu157Val
  • NC_000005.9:g.45645667G>C
Protein change:
L157V; LEU157VAL
Links:
OMIM: 602780.0013; dbSNP: rs1561230606
NCBI 1000 Genomes Browser:
rs1561230606
Molecular consequence:
  • NM_021072.4:c.469C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Generalized epilepsy with febrile seizures plus, type 10
Synonyms:
GEFS+, TYPE 10
Identifiers:
MONDO: MONDO:0032777; MedGen: C5193120; OMIM: 618482

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000924674OMIM
no assertion criteria provided
Pathogenic
(Jun 25, 2019) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability.

Bonzanni M, DiFrancesco JC, Milanesi R, Campostrini G, Castellotti B, Bucchi A, Baruscotti M, Ferrarese C, Franceschetti S, Canafoglia L, Ragona F, Freri E, Labate A, Gambardella A, Costa C, Rivolta I, Gellera C, Granata T, Barbuti A, DiFrancesco D.

Neurobiol Dis. 2018 Oct;118:55-63. doi: 10.1016/j.nbd.2018.06.012. Epub 2018 Jun 21.

PubMed [citation]
PMID:
29936235

Details of each submission

From OMIM, SCV000924674.1

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

Description

In a 19-year-old man with generalized epilepsy with febrile seizures plus-10 (GEFSP10; 618482), Bonzanni et al. (2018) identified a de novo heterozygous c.469C-G transversion (c.469C-G, GRCh37) in exon 2 of the HCN1 gene, resulting in a leu157-to-val (L157V) substitution at a conserved residue in transmembrane domain S1. The mutation was found by sequencing of an epilepsy gene panel. In vitro cellular functional expression studies showed that the mutation resulted in reduced current density compared to wildtype and increased current activation due to modified kinetic properties. Overall, these changes resulted in a dominant-negative effect with increased neuronal excitability.

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

Last Updated: Apr 23, 2022