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NM_001165963.4(SCN1A):c.2819C>T (p.Ser940Phe) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 23, 2016
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:
RCV000428224.1

Allele description

NM_001165963.4(SCN1A):c.2819C>T (p.Ser940Phe)

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.2819C>T (p.Ser940Phe)
HGVS:
  • NC_000002.12:g.166037903G>A
  • NG_011906.1:g.40737C>T
  • NM_001165963.4:c.2819C>TMANE SELECT
  • NM_001165964.3:c.2735C>T
  • NM_001202435.3:c.2819C>T
  • NM_001353948.2:c.2819C>T
  • NM_001353949.2:c.2786C>T
  • NM_001353950.2:c.2786C>T
  • NM_001353951.2:c.2786C>T
  • NM_001353952.2:c.2786C>T
  • NM_001353954.2:c.2783C>T
  • NM_001353955.2:c.2783C>T
  • NM_001353957.2:c.2735C>T
  • NM_001353958.2:c.2735C>T
  • NM_001353960.2:c.2732C>T
  • NM_001353961.2:c.377C>T
  • NM_006920.6:c.2786C>T
  • NP_001159435.1:p.Ser940Phe
  • NP_001159436.1:p.Ser912Phe
  • NP_001189364.1:p.Ser940Phe
  • NP_001340877.1:p.Ser940Phe
  • NP_001340878.1:p.Ser929Phe
  • NP_001340879.1:p.Ser929Phe
  • NP_001340880.1:p.Ser929Phe
  • NP_001340881.1:p.Ser929Phe
  • NP_001340883.1:p.Ser928Phe
  • NP_001340884.1:p.Ser928Phe
  • NP_001340886.1:p.Ser912Phe
  • NP_001340887.1:p.Ser912Phe
  • NP_001340889.1:p.Ser911Phe
  • NP_001340890.1:p.Ser126Phe
  • NP_008851.3:p.Ser929Phe
  • LRG_8:g.40737C>T
  • NC_000002.11:g.166894413G>A
  • NM_001165963.1:c.2819C>T
  • NR_148667.2:n.3172C>T
Protein change:
S126F
Links:
dbSNP: rs1057521080
NCBI 1000 Genomes Browser:
rs1057521080
Molecular consequence:
  • NM_001165963.4:c.2819C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.2735C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.2819C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.2819C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.2786C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.2786C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.2786C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.2786C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.2783C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.2783C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.2735C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.2735C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.2732C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.377C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.2786C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.3172C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000520961GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Sep 23, 2016) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000520961.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A S940F variant that is likely pathogenic has been identified in the SCN1A gene. The S940F variant has been previously reported in five unrelated individuals with SMEI or other seizure phenotypes consistent with SCN1A-related disorder; however, parental testing was not performed (Parihar et al., 2013; Sugawara et al., 2013; Wang et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S940F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the second homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with SCN1A-related disorder (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Jun 16, 2022