NM_001165963.4(SCN1A):c.5863A>G (p.Ile1955Val) AND Generalized epilepsy with febrile seizures plus, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 8, 2023
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:: RCV003455694.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5863A>G (p.Ile1955Val)]

NM_001165963.4(SCN1A):c.5863A>G (p.Ile1955Val)

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.5863A>G (p.Ile1955Val)

HGVS:

NC_000002.12:g.165991412T>C
NG_011906.1:g.87228A>G
NM_001165963.4:c.5863A>GMANE SELECT
NM_001165964.3:c.5779A>G
NM_001202435.3:c.5863A>G
NM_001353948.2:c.5863A>G
NM_001353949.2:c.5830A>G
NM_001353950.2:c.5830A>G
NM_001353951.2:c.5830A>G
NM_001353952.2:c.5830A>G
NM_001353954.2:c.5827A>G
NM_001353955.2:c.5827A>G
NM_001353957.2:c.5779A>G
NM_001353958.2:c.5779A>G
NM_001353960.2:c.5776A>G
NM_001353961.2:c.3421A>G
NM_006920.6:c.5830A>G
NP_001159435.1:p.Ile1955Val
NP_001159436.1:p.Ile1927Val
NP_001189364.1:p.Ile1955Val
NP_001340877.1:p.Ile1955Val
NP_001340878.1:p.Ile1944Val
NP_001340879.1:p.Ile1944Val
NP_001340880.1:p.Ile1944Val
NP_001340881.1:p.Ile1944Val
NP_001340883.1:p.Ile1943Val
NP_001340884.1:p.Ile1943Val
NP_001340886.1:p.Ile1927Val
NP_001340887.1:p.Ile1927Val
NP_001340889.1:p.Ile1926Val
NP_001340890.1:p.Ile1141Val
NP_008851.3:p.Ile1944Val
NP_008851.3:p.Ile1944Val
LRG_8t1:c.5830A>G
LRG_8:g.87228A>G
LRG_8p1:p.Ile1944Val
NC_000002.11:g.166847922T>C
NM_006920.4:c.5830A>G
NR_148667.2:n.6280A>G

Protein change:

I1141V

Molecular consequence:

NM_001165963.4:c.5863A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5779A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5863A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5863A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5830A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5830A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5830A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5830A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5827A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5827A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5779A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5779A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5776A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.3421A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5830A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.6280A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Generalized epilepsy with febrile seizures plus, type 2 (GEFSP2)
Synonyms:: GEFS+, TYPE 2
Identifiers:: MONDO: MONDO:0011461; MedGen: C1858673; Orphanet: 36387; OMIM: 604403

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004177160	Clinical Genomics Laboratory, Washington University in St. Louis	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 8, 2023)	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

SCV004177160

Clinical Genomics Laboratory, Washington University in St. Louis

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 8, 2023)

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Clinical Genomics Laboratory, Washington University in St. Louis, SCV004177160.1

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

Description

The SCN1A c.5863A>G (p.Ile1955Val) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by one submitter. This variant is only observed on 1/250,712 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This codon is in the cytoplasmic C terminus without known function and computational predictors suggest that the variant does not impact SCN1A function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine