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NM_001378969.1(KCND3):c.1174G>A (p.Val392Ile) AND Spinocerebellar ataxia type 19/22

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 8, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000460804.9

Allele description [Variation Report for NM_001378969.1(KCND3):c.1174G>A (p.Val392Ile)]

NM_001378969.1(KCND3):c.1174G>A (p.Val392Ile)

Gene:
KCND3:potassium voltage-gated channel subfamily D member 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p13.2
Genomic location:
Preferred name:
NM_001378969.1(KCND3):c.1174G>A (p.Val392Ile)
HGVS:
  • NC_000001.11:g.111787039C>T
  • NG_032011.2:g.207117G>A
  • NM_001378969.1:c.1174G>AMANE SELECT
  • NM_001378970.1:c.1174G>A
  • NM_004980.5:c.1174G>A
  • NM_172198.3:c.1174G>A
  • NP_001365898.1:p.Val392Ile
  • NP_001365899.1:p.Val392Ile
  • NP_004971.2:p.Val392Ile
  • NP_004971.2:p.Val392Ile
  • NP_751948.1:p.Val392Ile
  • LRG_445t1:c.1174G>A
  • LRG_445:g.207117G>A
  • LRG_445p1:p.Val392Ile
  • NC_000001.10:g.112329661C>T
  • NM_004980.4:c.1174G>A
  • Q9UK17:p.Val392Ile
Protein change:
V392I; VAL392ILE
Links:
UniProtKB: Q9UK17#VAR_067694; OMIM: 605411.0007; dbSNP: rs786205867
NCBI 1000 Genomes Browser:
rs786205867
Molecular consequence:
  • NM_001378969.1:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378970.1:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004980.5:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172198.3:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000548726Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 8, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with autopsy-negative sudden unexplained death.

Giudicessi JR, Ye D, Kritzberger CJ, Nesterenko VV, Tester DJ, Antzelevitch C, Ackerman MJ.

Hum Mutat. 2012 Jun;33(6):989-97. doi: 10.1002/humu.22058. Epub 2012 Mar 27.

PubMed [citation]
PMID:
22457051
PMCID:
PMC3518919

Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.

Wang J, Wen Y, Zhang Q, Yu S, Chen Y, Wu X, Zhang Y, Bao X.

Seizure. 2019 Mar;66:26-30. doi: 10.1016/j.seizure.2019.01.025. Epub 2019 Jan 28.

PubMed [citation]
PMID:
30776697
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000548726.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

ClinVar contains an entry for this variant (Variation ID: 192255). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCND3 function (PMID: 22457051). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCND3 protein function. This missense change has been observed in individual(s) with autosomal dominant KCND3-related conditions and/or sudden unexplained death or non-syndromic epileptic encephalopathy (PMID: 22457051, 30776697, 32921676). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 392 of the KCND3 protein (p.Val392Ile).

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

Last Updated: Oct 8, 2024