NM_001165963.4(SCN1A):c.4168G>A (p.Val1390Met) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Pathogenic (Last evaluated: Sep 10, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000804975.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4168G>A (p.Val1390Met)]

NM_001165963.4(SCN1A):c.4168G>A (p.Val1390Met)

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.4168G>A (p.Val1390Met)
HGVS:
  • NC_000002.12:g.166002588C>T
  • NG_011906.1:g.76052G>A
  • NM_001165963.4:c.4168G>AMANE SELECT
  • NM_001165963.4:c.4168G>A
  • NM_001165964.3:c.4084G>A
  • NM_001202435.3:c.4168G>A
  • NM_001353948.2:c.4168G>A
  • NM_001353949.2:c.4135G>A
  • NM_001353950.2:c.4135G>A
  • NM_001353951.2:c.4135G>A
  • NM_001353952.2:c.4135G>A
  • NM_001353954.2:c.4132G>A
  • NM_001353955.2:c.4132G>A
  • NM_001353957.2:c.4084G>A
  • NM_001353958.2:c.4084G>A
  • NM_001353960.2:c.4081G>A
  • NM_001353961.2:c.1726G>A
  • NM_006920.6:c.4135G>A
  • NP_001159435.1:p.Val1390Met
  • NP_001159436.1:p.Val1362Met
  • NP_001189364.1:p.Val1390Met
  • NP_001340877.1:p.Val1390Met
  • NP_001340878.1:p.Val1379Met
  • NP_001340879.1:p.Val1379Met
  • NP_001340880.1:p.Val1379Met
  • NP_001340881.1:p.Val1379Met
  • NP_001340883.1:p.Val1378Met
  • NP_001340884.1:p.Val1378Met
  • NP_001340886.1:p.Val1362Met
  • NP_001340887.1:p.Val1362Met
  • NP_001340889.1:p.Val1361Met
  • NP_001340890.1:p.Val576Met
  • NP_008851.3:p.Val1379Met
  • LRG_8t1:c.4135G>A
  • LRG_8:g.76052G>A
  • NC_000002.11:g.166859098C>T
  • NM_001165963.1:c.4168G>A
  • NM_006920.4:c.4135G>A
  • NR_148667.2:n.4585G>A
Protein change:
V1361M
Links:
UniProtKB/Swiss-Prot: VAR_029699; dbSNP: rs121917986
NCBI 1000 Genomes Browser:
rs121917986
Molecular consequence:
  • NM_001165963.4:c.4168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4084G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.4168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.4168G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.4135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.4135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.4135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.4135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.4132G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.4132G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4084G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4084G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4081G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.4135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.4585G>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
SCV000944916Invitaecriteria provided, single submitter
Pathogenic
(Sep 10, 2018)
germlineclinical testing

PubMed (8)
[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

A catalog of SCN1A variants.

Lossin C.

Brain Dev. 2009 Feb;31(2):114-30. doi: 10.1016/j.braindev.2008.07.011. Epub 2008 Sep 19. Review. Erratum in: Brain Dev. 2014 Jan;36(1):90.

PubMed [citation]
PMID:
18804930

Dravet syndrome: seizure control and gait in adults with different SCN1A mutations.

Rilstone JJ, Coelho FM, Minassian BA, Andrade DM.

Epilepsia. 2012 Aug;53(8):1421-8. doi: 10.1111/j.1528-1167.2012.03583.x. Epub 2012 Jul 10.

PubMed [citation]
PMID:
22780858
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000944916.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces valine with methionine at codon 1390 of the SCN1A protein (p.Val1390Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Dravet syndrome; in several of these cases, it was observed to be de novo (PMID: 12083760, 20431604, 23762420, 22780858, 29141279). This variant is also known as c.A3169G p.V1380M in the literature. ClinVar contains an entry for this variant (Variation ID: 68537). This variant identified in the SCN1A gene is located in the extracellular D3-P3 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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