ClinVar Genomic variation as it relates to human health
NM_001165963.4(SCN1A):c.4831G>T (p.Val1611Phe)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001165963.4(SCN1A):c.4831G>T (p.Val1611Phe)
Variation ID: 12895 Accession: VCV000012895.3
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q24.3 2: 165994167 (GRCh38) [ NCBI UCSC ] 2: 166850677 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 31, 2013 Apr 15, 2024 Mar 1, 2003 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001165963.4:c.4831G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001159435.1:p.Val1611Phe missense NM_001165964.3:c.4747G>T NP_001159436.1:p.Val1583Phe missense NM_001202435.3:c.4831G>T NP_001189364.1:p.Val1611Phe missense NM_001353948.2:c.4831G>T NP_001340877.1:p.Val1611Phe missense NM_001353949.2:c.4798G>T NP_001340878.1:p.Val1600Phe missense NM_001353950.2:c.4798G>T NP_001340879.1:p.Val1600Phe missense NM_001353951.2:c.4798G>T NP_001340880.1:p.Val1600Phe missense NM_001353952.2:c.4798G>T NP_001340881.1:p.Val1600Phe missense NM_001353954.2:c.4795G>T NP_001340883.1:p.Val1599Phe missense NM_001353955.2:c.4795G>T NP_001340884.1:p.Val1599Phe missense NM_001353957.2:c.4747G>T NP_001340886.1:p.Val1583Phe missense NM_001353958.2:c.4747G>T NP_001340887.1:p.Val1583Phe missense NM_001353960.2:c.4744G>T NP_001340889.1:p.Val1582Phe missense NM_001353961.2:c.2389G>T NP_001340890.1:p.Val797Phe missense NM_006920.6:c.4798G>T NP_008851.3:p.Val1600Phe missense NR_148667.2:n.5248G>T non-coding transcript variant NC_000002.12:g.165994167C>A NC_000002.11:g.166850677C>A NG_011906.1:g.84473G>T LRG_8:g.84473G>T LRG_8t1:c.4798G>T - Protein change
- V1611F, V1600F, V1582F, V1599F, V797F, V1583F
- Other names
- -
- Canonical SPDI
- NC_000002.12:165994166:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Normal slope of fast inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0074]
- Normal slope of slow inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0122]
- Normal voltage dependence of slow inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0118]
- Normal recovery from slow inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0108]
- Normal slope of activation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0036]
- Acceleration of entry into slow inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0103]
- Acceleration of fast inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0046]
- Decrease of decay in current amplitude in use dependence Functional Epilepsy Nomenclature for Ion Channels [FENICS-0133]
- Mild decrease in peak current Functional Epilepsy Nomenclature for Ion Channels [FENICS-0085]
- Mild hyperpolarizing shift of voltage dependence of fast inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0067]
- Moderate hyperpolarizing shift of voltage dependence of activation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0030]
- Moderate increase in persistent current Functional Epilepsy Nomenclature for Ion Channels [FENICS-0042]
- Normal rate of recovery from fast inactivation Functional Epilepsy Nomenclature for Ion Channels [FENICS-0054]
- Overall mixed or unclear functional effect with respect to biophysical channel activity Functional Epilepsy Nomenclature for Ion Channels [FENICS-0148]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
SCN1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2180 | 4526 | |
LOC102724058 | - | - | - | GRCh38 | - | 2292 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (3) |
no assertion criteria provided
|
Mar 1, 2003 | RCV000013756.28 | |
Pathogenic (1) |
no assertion criteria provided
|
Mar 1, 2003 | RCV000013757.25 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 01, 2003)
|
no assertion criteria provided
Method: literature only
|
GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 2
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034004.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 20, 2020 |
Comment on evidence:
In a patient with a Dravet syndrome (DRVT; 607208), Fujiwara et al. (2003) identified a heterozygous c.4831G-T transversion in the SCN1A gene, resulting in a … (more)
In a patient with a Dravet syndrome (DRVT; 607208), Fujiwara et al. (2003) identified a heterozygous c.4831G-T transversion in the SCN1A gene, resulting in a val1611-to-phe (V1611F) substitution in domain IV of the protein. The patient's mother, who also had the mutation, had a history of febrile seizures consistent with GEFS+ (GEFSP2; 604403). The V1611F substitution was not identified in 93 control chromosomes. (less)
|
|
Pathogenic
(Mar 01, 2003)
|
no assertion criteria provided
Method: literature only
|
DRAVET SYNDROME
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000034003.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 20, 2020 |
Comment on evidence:
In a patient with a Dravet syndrome (DRVT; 607208), Fujiwara et al. (2003) identified a heterozygous c.4831G-T transversion in the SCN1A gene, resulting in a … (more)
In a patient with a Dravet syndrome (DRVT; 607208), Fujiwara et al. (2003) identified a heterozygous c.4831G-T transversion in the SCN1A gene, resulting in a val1611-to-phe (V1611F) substitution in domain IV of the protein. The patient's mother, who also had the mutation, had a history of febrile seizures consistent with GEFS+ (GEFSP2; 604403). The V1611F substitution was not identified in 93 control chromosomes. (less)
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Severe myoclonic epilepsy in infancy
Affected status: not applicable
Allele origin:
not applicable
|
Channelopathy-Associated Epilepsy Research Center
Accession: SCV004809300.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Method: whole-cell patch-clamp recording
Result:
Mild decrease in peak current;Moderate hyperpolarizing shift of voltage dependence of activation;Normal slope of activation;Mild hyperpolarizing shift of voltage dependence of fast inactivation;Normal slope of fast inactivation;Normal rate of recovery from fast inactivation;Acceleration of fast inactivation;Moderate increase in persistent current;Acceleration of entry into slow inactivation;Normal recovery from slow inactivation;Normal voltage dependence of slow inactivation;Normal slope of slow inactivation;Decrease of decay in current amplitude in use dependence;Overall mixed or unclear functional effect with respect to biophysical channel activity
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
Severe myoclonic epilepsy in infancy
Affected status: not provided
Allele origin:
germline
|
UniProtKB/Swiss-Prot
Accession: SCV000091047.1
First in ClinVar: Oct 31, 2013 Last updated: Oct 31, 2013
Comment:
Intractable childhood epilepsy with generalized tonic-clonic seizures
|
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
Mild decrease in peak current
Moderate hyperpolarizing shift of voltage dependence of activation
Normal slope of activation
Mild hyperpolarizing shift of voltage dependence of fast inactivation
Normal slope of fast inactivation
Normal rate of recovery from fast inactivation
Acceleration of fast inactivation
Moderate increase in persistent current
Acceleration of entry into slow inactivation
Normal recovery from slow inactivation
Normal voltage dependence of slow inactivation
Normal slope of slow inactivation
Decrease of decay in current amplitude in use dependence
Overall mixed or unclear functional effect with respect to biophysical channel activity
|
|
|
Channelopathy-Associated Epilepsy Research Center
Accession: SCV004809300.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures. | Rhodes TH | The Journal of physiology | 2005 | PMID: 16210358 |
Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. | Fujiwara T | Brain : a journal of neurology | 2003 | PMID: 12566275 |
Text-mined citations for rs121918630 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.