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NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 1, 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:
RCV002613187.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)]

NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)

Gene:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.1184C>A (p.Ala395Asp)
HGVS:
  • NC_000002.12:g.166046963G>T
  • NG_011906.1:g.31677C>A
  • NM_001165963.1:c.1184C>A
  • NM_001165963.4:c.1184C>AMANE SELECT
  • NM_001165964.3:c.1184C>A
  • NM_001202435.3:c.1184C>A
  • NM_001353948.2:c.1184C>A
  • NM_001353949.2:c.1184C>A
  • NM_001353950.2:c.1184C>A
  • NM_001353951.2:c.1184C>A
  • NM_001353952.2:c.1184C>A
  • NM_001353954.2:c.1184C>A
  • NM_001353955.2:c.1184C>A
  • NM_001353957.2:c.1184C>A
  • NM_001353958.2:c.1184C>A
  • NM_001353960.2:c.1184C>A
  • NM_001353961.2:c.-1242C>A
  • NM_006920.6:c.1184C>A
  • NP_001159435.1:p.Ala395Asp
  • NP_001159436.1:p.Ala395Asp
  • NP_001189364.1:p.Ala395Asp
  • NP_001340877.1:p.Ala395Asp
  • NP_001340878.1:p.Ala395Asp
  • NP_001340879.1:p.Ala395Asp
  • NP_001340880.1:p.Ala395Asp
  • NP_001340881.1:p.Ala395Asp
  • NP_001340883.1:p.Ala395Asp
  • NP_001340884.1:p.Ala395Asp
  • NP_001340886.1:p.Ala395Asp
  • NP_001340887.1:p.Ala395Asp
  • NP_001340889.1:p.Ala395Asp
  • NP_008851.3:p.Ala395Asp
  • NP_008851.3:p.Ala395Asp
  • LRG_8t1:c.1184C>A
  • LRG_8:g.31677C>A
  • LRG_8p1:p.Ala395Asp
  • NC_000002.11:g.166903473G>T
  • NM_006920.4:c.1184C>A
  • NR_148667.2:n.1570C>A
Protein change:
A395D
Molecular consequence:
  • NM_001353961.2:c.-1242C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001165963.4:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.1570C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002950936Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Oct 1, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

The spectrum of SCN1A-related infantile epileptic encephalopathies.

Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A; Infantile Epileptic Encephalopathy Referral Consortium., Sutherland G, Berkovic SF, et al.

Brain. 2007 Mar;130(Pt 3):843-52.

PubMed [citation]
PMID:
17347258

Mutation spectrum of the SCN1A gene in a Hungarian population with epilepsy.

Till Á, Zima J, Fekete A, Bene J, Czakó M, Szabó A, Melegh B, Hadzsiev K.

Seizure. 2020 Jan;74:8-13. doi: 10.1016/j.seizure.2019.10.019. Epub 2019 Nov 8.

PubMed [citation]
PMID:
31765958
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002950936.2

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

Description

This variant disrupts the p.Ala395 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 17347258), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individual(s) with SCN1A-related conditions (PMID: 31765958). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 395 of the SCN1A protein (p.Ala395Asp).

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

Last Updated: Sep 29, 2024