NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln) AND Severe myoclonic epilepsy in infancy

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 16, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000059432.12

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln)]

NM_001165963.4(SCN1A):c.4934G>A (p.Arg1645Gln)

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.4934G>A (p.Arg1645Gln)

Other names:

p.R1645Q:CGA>CAA

HGVS:

NC_000002.12:g.165992341C>T
NG_011906.1:g.86299G>A
NM_001165963.1:c.[4934G>A]
NM_001165963.4:c.4934G>AMANE SELECT
NM_001165963.4:c.4934G>A
NM_001165964.3:c.4850G>A
NM_001202435.3:c.4934G>A
NM_001353948.2:c.4934G>A
NM_001353949.2:c.4901G>A
NM_001353950.2:c.4901G>A
NM_001353951.2:c.4901G>A
NM_001353952.2:c.4901G>A
NM_001353954.2:c.4898G>A
NM_001353955.2:c.4898G>A
NM_001353957.2:c.4850G>A
NM_001353958.2:c.4850G>A
NM_001353960.2:c.4847G>A
NM_001353961.2:c.2492G>A
NM_006920.6:c.4901G>A
NP_001159435.1:p.Arg1645Gln
NP_001159436.1:p.Arg1617Gln
NP_001189364.1:p.Arg1645Gln
NP_001340877.1:p.Arg1645Gln
NP_001340878.1:p.Arg1634Gln
NP_001340879.1:p.Arg1634Gln
NP_001340880.1:p.Arg1634Gln
NP_001340881.1:p.Arg1634Gln
NP_001340883.1:p.Arg1633Gln
NP_001340884.1:p.Arg1633Gln
NP_001340886.1:p.Arg1617Gln
NP_001340887.1:p.Arg1617Gln
NP_001340889.1:p.Arg1616Gln
NP_001340890.1:p.Arg831Gln
NP_008851.3:p.Arg1634Gln
LRG_8t1:c.4901G>A
LRG_8:g.86299G>A
NC_000002.11:g.166848851C>T
NM_001165963.1:c.4934G>A
NM_001165963.1:c.[4934G>A]
NM_006920.4:c.4901G>A
NR_148667.2:n.5351G>A

Protein change:

R1616Q

Links:

UniProtKB/Swiss-Prot: VAR_064269; dbSNP: rs121917976

NCBI 1000 Genomes Browser:

rs121917976

Molecular consequence:

NM_001165963.4:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.4934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.4898G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.4898G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.4850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.4847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.4901G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5351G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Severe myoclonic epilepsy in infancy (DRVT)
Synonyms:: Epilepsy, Myoclonic, Infantile, Severe; Dravet syndrome; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100135; MedGen: C0751122; Orphanet: 33069; OMIM: 607208

Recent activity

Clear Turn Off Turn On

VMA10 [Saccharomyces cerevisiae S288C]
VMA10 [Saccharomyces cerevisiae S288C]
Gene ID:856435

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000090956	UniProtKB/Swiss-Prot	no classification provided	not provided	unknown	not provided	PubMed (1) [See all records that cite this PMID]
SCV000494514	Neurogenetics Laboratory - MEYER, AOU Meyer	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 16, 2016)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002072919	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000090956

UniProtKB/Swiss-Prot

no classification provided

not provided

unknown

not provided

PubMed (1)
[See all records that cite this PMID]

SCV000494514

Neurogenetics Laboratory - MEYER, AOU Meyer

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 16, 2016)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002072919

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	1	no	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

The spectrum of SCN1A-related infantile epileptic encephalopathies.

Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A; Infantile Epileptic Encephalopathy Referral Consortium., Sutherland G, Berkovic SF, et al.

Brain. 2007 Mar;130(Pt 3):843-52.

PubMed [citation]

PMID:: 17347258

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From UniProtKB/Swiss-Prot, SCV000090956.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Neurogenetics Laboratory - MEYER, AOU Meyer, SCV000494514.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV002072919.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The missense variant p.R1645Q in SCN1A (NM_001165963.4) has ben previously reported in multiple patients with Dravet syndrome including one where it was confirmed to be de novo (Harkin LA et al; Parrini E et al). The variant has been submitted to ClinVar as Pathogenic.The missense variant c.4934G>A (p.R1645Q) in SCN1A (NM_001165963.4) is not observed in the large population cohorts of the gnomAD and 1000 Genomes datasets (Exome Aggregation Consortium et al., 2016; 1000 Genomes Consortium et al., 2015). The p.R1645Q missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 1645 of SCN1A is conserved in all mammalian species. The nucleotide c.4934 in SCN1A is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 2, 2024

ClinVar

Relating variation to medicine