NM_001165963.4(SCN1A):c.1060G>C (p.Ala354Pro) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Uncertain significance (Last evaluated: Jun 3, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001219108.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1060G>C (p.Ala354Pro)]

NM_001165963.4(SCN1A):c.1060G>C (p.Ala354Pro)

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.1060G>C (p.Ala354Pro)
HGVS:
  • NC_000002.12:g.166047737C>G
  • NG_011906.1:g.30903G>C
  • NM_001165963.4:c.1060G>CMANE SELECT
  • NM_001165964.3:c.1060G>C
  • NM_001202435.3:c.1060G>C
  • NM_001353948.2:c.1060G>C
  • NM_001353949.2:c.1060G>C
  • NM_001353950.2:c.1060G>C
  • NM_001353951.2:c.1060G>C
  • NM_001353952.2:c.1060G>C
  • NM_001353954.2:c.1060G>C
  • NM_001353955.2:c.1060G>C
  • NM_001353957.2:c.1060G>C
  • NM_001353958.2:c.1060G>C
  • NM_001353960.2:c.1060G>C
  • NM_001353961.2:c.-1366G>C
  • NM_006920.6:c.1060G>C
  • NP_001159435.1:p.Ala354Pro
  • NP_001159436.1:p.Ala354Pro
  • NP_001189364.1:p.Ala354Pro
  • NP_001340877.1:p.Ala354Pro
  • NP_001340878.1:p.Ala354Pro
  • NP_001340879.1:p.Ala354Pro
  • NP_001340880.1:p.Ala354Pro
  • NP_001340881.1:p.Ala354Pro
  • NP_001340883.1:p.Ala354Pro
  • NP_001340884.1:p.Ala354Pro
  • NP_001340886.1:p.Ala354Pro
  • NP_001340887.1:p.Ala354Pro
  • NP_001340889.1:p.Ala354Pro
  • NP_008851.3:p.Ala354Pro
  • LRG_8:g.30903G>C
  • NC_000002.11:g.166904247C>G
  • NM_001165963.1:c.1060G>C
  • NM_001165963.3:c.1060G>C
  • NR_148667.2:n.1446G>C
Protein change:
A354P
Molecular consequence:
  • NM_001353961.2:c.-1366G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001165963.4:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.1446G>C - 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
SCV001391029Invitaecriteria provided, single submitter
Uncertain significance
(Jun 3, 2019)
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

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]
PMID:
25348405
PMCID:
PMC4384041

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
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001391029.1

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

Description

This sequence change replaces alanine with proline at codon 354 of the SCN1A protein (p.Ala354Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant identified in the SCN1A gene is located in the extracellular D1-P1 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 8, 2021

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