NM_001165963.4(SCN1A):c.5306A>C (p.Tyr1769Ser) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2022
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:: RCV001236640.9

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5306A>C (p.Tyr1769Ser)]

NM_001165963.4(SCN1A):c.5306A>C (p.Tyr1769Ser)

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.5306A>C (p.Tyr1769Ser)

HGVS:

NC_000002.12:g.165991969T>G
NG_011906.1:g.86671A>C
NM_001165963.4:c.5306A>CMANE SELECT
NM_001165964.3:c.5222A>C
NM_001202435.3:c.5306A>C
NM_001353948.2:c.5306A>C
NM_001353949.2:c.5273A>C
NM_001353950.2:c.5273A>C
NM_001353951.2:c.5273A>C
NM_001353952.2:c.5273A>C
NM_001353954.2:c.5270A>C
NM_001353955.2:c.5270A>C
NM_001353957.2:c.5222A>C
NM_001353958.2:c.5222A>C
NM_001353960.2:c.5219A>C
NM_001353961.2:c.2864A>C
NM_006920.6:c.5273A>C
NP_001159435.1:p.Tyr1769Ser
NP_001159436.1:p.Tyr1741Ser
NP_001189364.1:p.Tyr1769Ser
NP_001340877.1:p.Tyr1769Ser
NP_001340878.1:p.Tyr1758Ser
NP_001340879.1:p.Tyr1758Ser
NP_001340880.1:p.Tyr1758Ser
NP_001340881.1:p.Tyr1758Ser
NP_001340883.1:p.Tyr1757Ser
NP_001340884.1:p.Tyr1757Ser
NP_001340886.1:p.Tyr1741Ser
NP_001340887.1:p.Tyr1741Ser
NP_001340889.1:p.Tyr1740Ser
NP_001340890.1:p.Tyr955Ser
NP_008851.3:p.Tyr1758Ser
LRG_8:g.86671A>C
NC_000002.11:g.166848479T>G
NM_001165963.1:c.5306A>C
NR_148667.2:n.5723A>C

Protein change:

Y1740S

Links:

dbSNP: rs886039460

NCBI 1000 Genomes Browser:

rs886039460

Molecular consequence:

NM_001165963.4:c.5306A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5222A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5306A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5306A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5273A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5273A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5273A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5273A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5270A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5270A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5222A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5222A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5219A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2864A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5273A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5723A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001409372	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	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

SCV001409372

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

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, SCV001409372.5

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 1769 of the SCN1A protein (p.Tyr1769Ser). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (Invitae). 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. 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 expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 962732).

#	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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