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NM_001378969.1(KCND3):c.877_885dup (p.Arg296_Ile297insValPheArg) AND Spinocerebellar ataxia type 19/22

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 7, 2023
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:
RCV003389358.1

Allele description [Variation Report for NM_001378969.1(KCND3):c.877_885dup (p.Arg296_Ile297insValPheArg)]

NM_001378969.1(KCND3):c.877_885dup (p.Arg296_Ile297insValPheArg)

Gene:
KCND3:potassium voltage-gated channel subfamily D member 3 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
1p13.2
Genomic location:
Preferred name:
NM_001378969.1(KCND3):c.877_885dup (p.Arg296_Ile297insValPheArg)
HGVS:
  • NC_000001.11:g.111981848_111981856dup
  • NG_032011.2:g.12306_12314dup
  • NM_001378969.1:c.877_885dupMANE SELECT
  • NM_001378970.1:c.877_885dup
  • NM_004980.5:c.877_885dup
  • NM_172198.3:c.877_885dup
  • NP_001365898.1:p.Arg296_Ile297insValPheArg
  • NP_001365899.1:p.Arg296_Ile297insValPheArg
  • NP_004971.2:p.Arg296_Ile297insValPheArg
  • NP_004971.2:p.Arg296_Ile297insValPheArg
  • NP_751948.1:p.Arg296_Ile297insValPheArg
  • LRG_445t1:c.871_879dup
  • LRG_445:g.12306_12314dup
  • LRG_445p1:p.Arg296_Ile297insValPheArg
  • NC_000001.10:g.112524470_112524478dup
  • NM_004980.4:c.871_879dup
  • NM_004980.4:c.877_885dup
  • NM_004980.4:c.877_885dup
  • NM_004980.4:c.877_885dupCGCGTCTTC
Links:
OMIM: 605411.0008
Molecular consequence:
  • NM_001378969.1:c.877_885dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001378970.1:c.877_885dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_004980.5:c.877_885dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_172198.3:c.877_885dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:
Spinocerebellar ataxia type 19/22 (SCA19)
Synonyms:
Spinocerebellar ataxia 19; Spinocerebellar ataxia 22
Identifiers:
MONDO: MONDO:0011819; MedGen: C1846367; Orphanet: 98772; OMIM: 607346

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004101402OMIM
no assertion criteria provided
Pathogenic
(Nov 7, 2023) 		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

First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy.

Smets K, Duarri A, Deconinck T, Ceulemans B, van de Warrenburg BP, Züchner S, Gonzalez MA, Schüle R, Synofzik M, Van der Aa N, De Jonghe P, Verbeek DS, Baets J.

BMC Med Genet. 2015 Jul 21;16:51. doi: 10.1186/s12881-015-0200-3.

PubMed [citation]
PMID:
26189493
PMCID:
PMC4557545

Details of each submission

From OMIM, SCV004101402.1

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

Description

In a 10-year-old boy with spinocerebellar ataxia-19 (SCA19; 607346), Smets et al. (2015) identified a de novo heterozygous 9-bp duplication (c.877_885dupCGCGTCTTC, NM_004980.4) in the KCND3 gene, resulting in a 3-amino acid duplication (Arg293_Phe295dup) of the RVF (Arg-Val-Phe) domain in the S4 segment of Kv4.3. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family. Studies to assess the effects of the duplication showed that the mutant protein was properly localized in the cell, but that it had significantly decreased stability. The mutation caused a strong shift in the voltage-dependence of activation and inactivation.

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

Last Updated: Nov 3, 2024