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NM_001165963.4(SCN1A):c.5275C>T (p.Pro1759Ser) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 16, 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:
RCV000479372.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5275C>T (p.Pro1759Ser)]

NM_001165963.4(SCN1A):c.5275C>T (p.Pro1759Ser)

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.5275C>T (p.Pro1759Ser)
HGVS:
  • NC_000002.12:g.165992000G>A
  • NG_011906.1:g.86640C>T
  • NM_001165963.4:c.5275C>TMANE SELECT
  • NM_001165964.3:c.5191C>T
  • NM_001202435.3:c.5275C>T
  • NM_001353948.2:c.5275C>T
  • NM_001353949.2:c.5242C>T
  • NM_001353950.2:c.5242C>T
  • NM_001353951.2:c.5242C>T
  • NM_001353952.2:c.5242C>T
  • NM_001353954.2:c.5239C>T
  • NM_001353955.2:c.5239C>T
  • NM_001353957.2:c.5191C>T
  • NM_001353958.2:c.5191C>T
  • NM_001353960.2:c.5188C>T
  • NM_001353961.2:c.2833C>T
  • NM_006920.6:c.5242C>T
  • NP_001159435.1:p.Pro1759Ser
  • NP_001159436.1:p.Pro1731Ser
  • NP_001189364.1:p.Pro1759Ser
  • NP_001340877.1:p.Pro1759Ser
  • NP_001340878.1:p.Pro1748Ser
  • NP_001340879.1:p.Pro1748Ser
  • NP_001340880.1:p.Pro1748Ser
  • NP_001340881.1:p.Pro1748Ser
  • NP_001340883.1:p.Pro1747Ser
  • NP_001340884.1:p.Pro1747Ser
  • NP_001340886.1:p.Pro1731Ser
  • NP_001340887.1:p.Pro1731Ser
  • NP_001340889.1:p.Pro1730Ser
  • NP_001340890.1:p.Pro945Ser
  • NP_008851.3:p.Pro1748Ser
  • LRG_8:g.86640C>T
  • NC_000002.11:g.166848510G>A
  • NM_001165963.1:c.5275C>T
  • NR_148667.2:n.5692C>T
Protein change:
P1730S
Links:
dbSNP: rs1064794630
NCBI 1000 Genomes Browser:
rs1064794630
Molecular consequence:
  • NM_001165963.4:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.5191C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.5239C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.5239C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.5191C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.5191C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.5188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.2833C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.5692C>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
SCV000569609GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Mar 16, 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, SCV000569609.4

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

Description

A novel P1759S variant that is likely pathogenic has been identified in the SCN1A gene. The P1759S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. 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 P1759S 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. Additionally, this substitution alters a conserved position predicted to be within the extracellular loop between transmembrane segments S5 and S6 of the fourth homologous domain of the SCN1A protein. Furthermore, missense variants in nearby residues (G1754R, D1755G, C1756G, G1762E) have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. 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: Apr 23, 2022