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NM_001165963.4(SCN1A):c.4943G>T (p.Arg1648Leu) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 20, 2013
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:
RCV000188988.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4943G>T (p.Arg1648Leu)]

NM_001165963.4(SCN1A):c.4943G>T (p.Arg1648Leu)

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.4943G>T (p.Arg1648Leu)
Other names:
p.R1648L:CGT>CTT
HGVS:
  • NC_000002.12:g.165992332C>A
  • NG_011906.1:g.86308G>T
  • NM_001165963.4:c.4943G>TMANE SELECT
  • NM_001165964.3:c.4859G>T
  • NM_001202435.3:c.4943G>T
  • NM_001353948.2:c.4943G>T
  • NM_001353949.2:c.4910G>T
  • NM_001353950.2:c.4910G>T
  • NM_001353951.2:c.4910G>T
  • NM_001353952.2:c.4910G>T
  • NM_001353954.2:c.4907G>T
  • NM_001353955.2:c.4907G>T
  • NM_001353957.2:c.4859G>T
  • NM_001353958.2:c.4859G>T
  • NM_001353960.2:c.4856G>T
  • NM_001353961.2:c.2501G>T
  • NM_006920.6:c.4910G>T
  • NP_001159435.1:p.Arg1648Leu
  • NP_001159436.1:p.Arg1620Leu
  • NP_001189364.1:p.Arg1648Leu
  • NP_001340877.1:p.Arg1648Leu
  • NP_001340878.1:p.Arg1637Leu
  • NP_001340879.1:p.Arg1637Leu
  • NP_001340880.1:p.Arg1637Leu
  • NP_001340881.1:p.Arg1637Leu
  • NP_001340883.1:p.Arg1636Leu
  • NP_001340884.1:p.Arg1636Leu
  • NP_001340886.1:p.Arg1620Leu
  • NP_001340887.1:p.Arg1620Leu
  • NP_001340889.1:p.Arg1619Leu
  • NP_001340890.1:p.Arg834Leu
  • NP_008851.3:p.Arg1637Leu
  • LRG_8:g.86308G>T
  • NC_000002.11:g.166848842C>A
  • NM_001165963.1:c.4943G>T
  • NR_148667.2:n.5360G>T
Protein change:
R1619L
Links:
dbSNP: rs121918622
NCBI 1000 Genomes Browser:
rs121918622
Molecular consequence:
  • NM_001165963.4:c.4943G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4859G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.4943G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.4943G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.4910G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.4910G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.4910G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.4910G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.4907G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.4907G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4859G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4859G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4856G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.2501G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.4910G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.5360G>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
SCV000242619GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Feb 20, 2013) 		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, SCV000242619.11

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

Description

p.Arg1648Leu (CGT>CTT): c.4943 G>T in exon 26 of the SCN1A gene (NM_001165963.1) The Arg1648Leu missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Arg1648Leu in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a positively charged Arginine residue is replaced by an uncharged, non-polar Leucine residue. It alters a highly conserved position in the S4 (voltage sensor) segment of the fourth transmembrane domain, and multiple in silico algorithms predict it is damaging to protein structure/function. Additionally, a different amino acid substitution at the same amino acid position, Arg1648Cys, was found to co-segregate with GEFS+ in a large family and was also reported in an individual with Dravet syndrome (Ohmori et al., 2002). Another substitution at that position, Arg1648His, has been reported multiple times in association with Dravet syndrome, and functional studies indicate that it significantly impairs channel function (Escayg et al., 2000; Depienne et al., 2009; Alekov et al., 2000; Tang et al., 2009). Therefore, Arg1648Leu is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).

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

Last Updated: Apr 23, 2022