NM_001165963.4(SCN1A):c.4588T>C (p.Phe1530Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 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:: RCV001957807.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4588T>C (p.Phe1530Leu)]

NM_001165963.4(SCN1A):c.4588T>C (p.Phe1530Leu)

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.4588T>C (p.Phe1530Leu)

HGVS:

NC_000002.12:g.165994410A>G
NG_011906.1:g.84230T>C
NM_001165963.1:c.4588T>C
NM_001165963.4:c.4588T>CMANE SELECT
NM_001165964.3:c.4504T>C
NM_001202435.3:c.4588T>C
NM_001353948.2:c.4588T>C
NM_001353949.2:c.4555T>C
NM_001353950.2:c.4555T>C
NM_001353951.2:c.4555T>C
NM_001353952.2:c.4555T>C
NM_001353954.2:c.4552T>C
NM_001353955.2:c.4552T>C
NM_001353957.2:c.4504T>C
NM_001353958.2:c.4504T>C
NM_001353960.2:c.4501T>C
NM_001353961.2:c.2146T>C
NM_006920.6:c.4555T>C
NP_001159435.1:p.Phe1530Leu
NP_001159436.1:p.Phe1502Leu
NP_001189364.1:p.Phe1530Leu
NP_001340877.1:p.Phe1530Leu
NP_001340878.1:p.Phe1519Leu
NP_001340879.1:p.Phe1519Leu
NP_001340880.1:p.Phe1519Leu
NP_001340881.1:p.Phe1519Leu
NP_001340883.1:p.Phe1518Leu
NP_001340884.1:p.Phe1518Leu
NP_001340886.1:p.Phe1502Leu
NP_001340887.1:p.Phe1502Leu
NP_001340889.1:p.Phe1501Leu
NP_001340890.1:p.Phe716Leu
NP_008851.3:p.Phe1519Leu
LRG_8:g.84230T>C
NC_000002.11:g.166850920A>G
NR_148667.2:n.5005T>C

Protein change:

F1501L

Links:

dbSNP: rs1689724218

NCBI 1000 Genomes Browser:

rs1689724218

Molecular consequence:

NM_001165963.4:c.4588T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.4504T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.4588T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.4588T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.4555T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.4555T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.4555T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.4555T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.4552T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.4552T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.4504T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.4504T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.4501T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2146T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.4555T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5005T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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somatotropin isoform 2 precursor [Homo sapiens]
somatotropin isoform 2 precursor [Homo sapiens]
gi|13027814|ref|NP_072053.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002215935	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 21, 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

SCV002215935

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 21, 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002215935.3

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

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1530 of the SCN1A protein (p.Phe1530Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1438278). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN1A protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

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