p.Ala1783Val (GCG>GTG): c.5348 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The Ala1783Val variant has been previously reported as a de novo mutation in multiple unrelated patients with Dravet syndrome (Marini et al., 2007; Depienne et al., 2009). This substitution occurs at a position that is highly conserved across species and is located in transmembrane segment S6 in the fourth homologous domain. Therefore, Ala1783Val is considered a disease-causing mutation. The variant is found in INFANT-EPI panel(s).
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 5
- First in ClinVar:
- Oct 31, 2013
- Most recent Submission:
- May 16, 2022
- Last evaluated:
- Sep 2, 2021
- Accession:
- VCV000068571.8
- Variation ID:
- 68571
- Description:
- single nucleotide variant
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NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val)
- Allele ID
- 79463
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 2q24.3
- Genomic location
- 2: 165991927 (GRCh38) GRCh38 UCSC
- 2: 166848437 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001165963.4:c.5348C>T MANE Select NP_001159435.1:p.Ala1783Val missense NM_001165964.3:c.5264C>T NP_001159436.1:p.Ala1755Val missense NM_001202435.3:c.5348C>T NP_001189364.1:p.Ala1783Val missense NM_001353948.2:c.5348C>T NP_001340877.1:p.Ala1783Val missense NM_001353949.2:c.5315C>T NP_001340878.1:p.Ala1772Val missense NM_001353950.2:c.5315C>T NP_001340879.1:p.Ala1772Val missense NM_001353951.2:c.5315C>T NP_001340880.1:p.Ala1772Val missense NM_001353952.2:c.5315C>T NP_001340881.1:p.Ala1772Val missense NM_001353954.2:c.5312C>T NP_001340883.1:p.Ala1771Val missense NM_001353955.2:c.5312C>T NP_001340884.1:p.Ala1771Val missense NM_001353957.2:c.5264C>T NP_001340886.1:p.Ala1755Val missense NM_001353958.2:c.5264C>T NP_001340887.1:p.Ala1755Val missense NM_001353960.2:c.5261C>T NP_001340889.1:p.Ala1754Val missense NM_001353961.2:c.2906C>T NP_001340890.1:p.Ala969Val missense NM_006920.6:c.5315C>T NP_008851.3:p.Ala1772Val missense NR_148667.2:n.5765C>T NC_000002.12:g.165991927G>A NC_000002.11:g.166848437G>A NG_011906.1:g.86713C>T LRG_8:g.86713C>T LRG_8t1:c.5315C>T - Protein change
- A1772V, A1783V, A969V, A1754V, A1771V, A1755V
- Other names
- p.A1783V:GCG>GTG
- Canonical SPDI
- NC_000002.12:165991926:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- dbSNP: rs121917921
- ClinGen: CA285024
- UniProtKB/Swiss-Prot: VAR_064345
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 2 | criteria provided, multiple submitters, no conflicts | Jun 2, 2016 | RCV000189000.6 | |
| Pathogenic | 2 | criteria provided, single submitter | Dec 20, 2014 | RCV000059446.5 | |
| Pathogenic | 1 | criteria provided, single submitter | Sep 2, 2021 | RCV001207693.4 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| SCN1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1646 | 3367 | |
| LOC102724058 | - | - | - | GRCh38 | - | 1673 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Dec 20, 2014)
|
criteria provided, single submitter
Method: research
|
Dravet syndrome
Affected status: yes
Allele origin:
de novo
|
Center for Bioinformatics, Peking University
Additional submitter:
Pediatric Department, Peking University First Hospital
Study: University Clinical Cooperation “985 Project” PKU-2014-1-1
Accession: SCV000221927.1 First in ClinVar: Jul 02, 2015 Last updated: Jul 02, 2015
Comment:
Dravet syndrome (DS) probands were recruited from the outpatient and inpatient child neurology units of Peking University First Hospital from 2005 till present. The study … (more)
Dravet syndrome (DS) probands were recruited from the outpatient and inpatient child neurology units of Peking University First Hospital from 2005 till present. The study was approved by the Ethics Committee of Peking University First Hospital and the Institutional Review Board at Peking University. Participants or their parents provided written informed consent before enrollment. We collected a total of 267 mutations from 255 families with probands diagnosed with DS in China. All probands fulfilled the clinical diagnostic criteria. (less)
|
Number of individuals with the variant: 1
Ethnicity/Population group: Chinese
|
|
|
Pathogenic
(Jun 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins NTD LLC (GA)
Accession: SCV000341355.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Sex: mixed
|
|
|
Pathogenic
(Mar 12, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000242631.11
First in ClinVar: Aug 07, 2015 Last updated: Dec 15, 2018 |
Comment:
p.Ala1783Val (GCG>GTG): c.5348 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The Ala1783Val variant has been previously reported as a de novo mutation in … (more)
p.Ala1783Val (GCG>GTG): c.5348 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The Ala1783Val variant has been previously reported as a de novo mutation in multiple unrelated patients with Dravet syndrome (Marini et al., 2007; Depienne et al., 2009). This substitution occurs at a position that is highly conserved across species and is located in transmembrane segment S6 in the fourth homologous domain. Therefore, Ala1783Val is considered a disease-causing mutation. The variant is found in INFANT-EPI panel(s). (less)
|
|
|
Pathogenic
(Sep 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Early infantile epileptic encephalopathy with suppression bursts
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001379057.3
First in ClinVar: Jul 16, 2020 Last updated: May 16, 2022 |
Comment:
This sequence change replaces alanine with valine at codon 1783 of the SCN1A protein (p.Ala1783Val). The alanine residue is highly conserved and there is a … (more)
This sequence change replaces alanine with valine at codon 1783 of the SCN1A protein (p.Ala1783Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 17561957, 18930999, 29460957). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68571). 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. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
not provided
(-)
|
no assertion provided
Method: not provided
|
Severe myoclonic epilepsy in infancy
Affected status: not provided
Allele origin:
unknown
|
UniProtKB/Swiss-Prot
Accession: SCV000090971.1
First in ClinVar: Oct 31, 2013 Last updated: Oct 31, 2013 |
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mosaicism of de novo pathogenic SCN1A variants in epilepsy is a frequent phenomenon that correlates with variable phenotypes. | de Lange IM | Epilepsia | 2018 | PMID: 29460957 |
| Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome. | Xu X | Human mutation | 2015 | PMID: 26096185 |
| Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. | Depienne C | Journal of medical genetics | 2009 | PMID: 18930999 |
| Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. | Marini C | Epilepsia | 2007 | PMID: 17561957 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN1A | - | - | - | - |
| http://www.openbioinformatics.org/annovar/annovar_startup.html | - | - | - | - |
Text-mined citations for rs121917921...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Jun 24, 2022