U.S. flag

An official website of the United States government

NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 25, 2022
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:
RCV001056663.8

Allele description [Variation Report for NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)]

NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)

Gene:
KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.33
Genomic location:
Preferred name:
NM_172107.4(KCNQ2):c.1004C>T (p.Pro335Leu)
Other names:
p.P335L:CCG>CTG
HGVS:
  • NC_000020.11:g.63438644G>A
  • NG_009004.2:g.38997C>T
  • NM_004518.6:c.1004C>T
  • NM_172106.3:c.1004C>T
  • NM_172107.4:c.1004C>TMANE SELECT
  • NM_172108.5:c.1004C>T
  • NM_172109.3:c.1004C>T
  • NP_004509.2:p.Pro335Leu
  • NP_742104.1:p.Pro335Leu
  • NP_742105.1:p.Pro335Leu
  • NP_742106.1:p.Pro335Leu
  • NP_742107.1:p.Pro335Leu
  • NC_000020.10:g.62069997G>A
  • NM_172107.2:c.1004C>T
Protein change:
P335L
Links:
dbSNP: rs796052641
NCBI 1000 Genomes Browser:
rs796052641
Molecular consequence:
  • NM_004518.6:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172106.3:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172107.4:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172108.5:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172109.3:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Severe decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0087]
  • Severe hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0031]
  • Severe slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0015]

Condition(s)

Name:
Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:
Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:
MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001221116Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 25, 2022) 		germlineclinical testing

PubMed (3)
[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

Large-scale discovery of novel genetic causes of developmental disorders.

Deciphering Developmental Disorders Study..

Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.

PubMed [citation]
PMID:
25533962
PMCID:
PMC5955210

Spatial Clustering of de Novo Missense Mutations Identifies Candidate Neurodevelopmental Disorder-Associated Genes.

Lelieveld SH, Wiel L, Venselaar H, Pfundt R, Vriend G, Veltman JA, Brunner HG, Vissers LELM, Gilissen C.

Am J Hum Genet. 2017 Sep 7;101(3):478-484. doi: 10.1016/j.ajhg.2017.08.004. Epub 2017 Aug 31.

PubMed [citation]
PMID:
28867141
PMCID:
PMC5591029
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001221116.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro335 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 205892). This missense change has been observed in individual(s) with seizures and developmental delay (PMID: 25533962, 28867141; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 335 of the KCNQ2 protein (p.Pro335Leu).

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

Last Updated: Oct 8, 2024