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NM_001165963.4(SCN1A):c.4997C>T (p.Ser1666Phe) AND Developmental and epileptic encephalopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 5, 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:
RCV002515208.4

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4997C>T (p.Ser1666Phe)]

NM_001165963.4(SCN1A):c.4997C>T (p.Ser1666Phe)

Genes:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.4997C>T (p.Ser1666Phe)
HGVS:
  • NC_000002.12:g.165992278G>A
  • NG_011906.1:g.86362C>T
  • NM_001165963.4:c.4997C>TMANE SELECT
  • NM_001165964.3:c.4913C>T
  • NM_001202435.3:c.4997C>T
  • NM_001353948.2:c.4997C>T
  • NM_001353949.2:c.4964C>T
  • NM_001353950.2:c.4964C>T
  • NM_001353951.2:c.4964C>T
  • NM_001353952.2:c.4964C>T
  • NM_001353954.2:c.4961C>T
  • NM_001353955.2:c.4961C>T
  • NM_001353957.2:c.4913C>T
  • NM_001353958.2:c.4913C>T
  • NM_001353960.2:c.4910C>T
  • NM_001353961.2:c.2555C>T
  • NM_006920.6:c.4964C>T
  • NP_001159435.1:p.Ser1666Phe
  • NP_001159436.1:p.Ser1638Phe
  • NP_001189364.1:p.Ser1666Phe
  • NP_001340877.1:p.Ser1666Phe
  • NP_001340878.1:p.Ser1655Phe
  • NP_001340879.1:p.Ser1655Phe
  • NP_001340880.1:p.Ser1655Phe
  • NP_001340881.1:p.Ser1655Phe
  • NP_001340883.1:p.Ser1654Phe
  • NP_001340884.1:p.Ser1654Phe
  • NP_001340886.1:p.Ser1638Phe
  • NP_001340887.1:p.Ser1638Phe
  • NP_001340889.1:p.Ser1637Phe
  • NP_001340890.1:p.Ser852Phe
  • NP_008851.3:p.Ser1655Phe
  • LRG_8:g.86362C>T
  • NC_000002.11:g.166848788G>A
  • NM_001165963.1:c.4997C>T
  • NR_148667.2:n.5414C>T
Protein change:
S1637F
Links:
dbSNP: rs794726760
NCBI 1000 Genomes Browser:
rs794726760
Molecular consequence:
  • NM_001165963.4:c.4997C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.4997C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.4997C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.4964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.4964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.4964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.4964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.4961C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.4961C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4910C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.2555C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.4964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.5414C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Developmental and epileptic encephalopathy
Identifiers:
MONDO: MONDO:0100620; MedGen: C5779964

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003524747Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 5, 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

RET-like immunostaining of spinal motoneurons in amyotrophic lateral sclerosis.

Duberley RM, Johnson IP, Martin JE, Anand P.

Brain Res. 1998 Apr 13;789(2):351-4.

PubMed [citation]
PMID:
9573403

Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients.

Fernández-Marmiesse A, Roca I, Díaz-Flores F, Cantarín V, Pérez-Poyato MS, Fontalba A, Laranjeira F, Quintans S, Moldovan O, Felgueroso B, Rodríguez-Pedreira M, Simón R, Camacho A, Quijada P, Ibanez-Mico S, Domingno MR, Benito C, Calvo R, Pérez-Cejas A, Carrasco ML, Ramos F, Couce ML, et al.

Front Neurosci. 2019;13:1135. doi: 10.3389/fnins.2019.01135.

PubMed [citation]
PMID:
31780880
PMCID:
PMC6856296
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524747.3

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

Description

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 SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 189922). This missense change has been observed in individual(s) with Dravet syndrome and/or epileptic encephalopathy (PMID: 9573403, 31780880). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1666 of the SCN1A protein (p.Ser1666Phe).

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

Last Updated: Jul 13, 2025