NM_001165963.4(SCN1A):c.5905_5908dup (p.Thr1970fs) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 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:: RCV003098974.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5905_5908dup (p.Thr1970fs)]

NM_001165963.4(SCN1A):c.5905_5908dup (p.Thr1970fs)

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

Duplication

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.5905_5908dup (p.Thr1970fs)

HGVS:

NC_000002.12:g.165991367_165991370dup
NG_011906.1:g.87270_87273dup
NM_001165963.4:c.5905_5908dupMANE SELECT
NM_001165964.3:c.5821_5824dup
NM_001202435.3:c.5905_5908dup
NM_001353948.2:c.5905_5908dup
NM_001353949.2:c.5872_5875dup
NM_001353950.2:c.5872_5875dup
NM_001353951.2:c.5872_5875dup
NM_001353952.2:c.5872_5875dup
NM_001353954.2:c.5869_5872dup
NM_001353955.2:c.5869_5872dup
NM_001353957.2:c.5821_5824dup
NM_001353958.2:c.5821_5824dup
NM_001353960.2:c.5818_5821dup
NM_001353961.2:c.3463_3466dup
NM_006920.6:c.5872_5875dup
NP_001159435.1:p.Thr1970fs
NP_001159436.1:p.Thr1942fs
NP_001189364.1:p.Thr1970fs
NP_001340877.1:p.Thr1970fs
NP_001340878.1:p.Thr1959fs
NP_001340879.1:p.Thr1959fs
NP_001340880.1:p.Thr1959fs
NP_001340881.1:p.Thr1959fs
NP_001340883.1:p.Thr1958fs
NP_001340884.1:p.Thr1958fs
NP_001340886.1:p.Thr1942fs
NP_001340887.1:p.Thr1942fs
NP_001340889.1:p.Thr1941fs
NP_001340890.1:p.Thr1156fs
NP_008851.3:p.Thr1959Asnfs
NP_008851.3:p.Thr1959fs
LRG_8t1:c.5872_5875dup
LRG_8:g.87270_87273dup
LRG_8p1:p.Thr1959Asnfs
NC_000002.11:g.166847876_166847877insTAAT
NC_000002.11:g.166847877_166847880dup
NM_006920.4:c.5872_5875dup
NR_148667.2:n.6322_6325dup

Protein change:

T1156fs

Molecular consequence:

NM_001165963.4:c.5905_5908dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001165964.3:c.5821_5824dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001202435.3:c.5905_5908dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353948.2:c.5905_5908dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353949.2:c.5872_5875dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353950.2:c.5872_5875dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353951.2:c.5872_5875dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353952.2:c.5872_5875dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353954.2:c.5869_5872dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353955.2:c.5869_5872dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353957.2:c.5821_5824dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353958.2:c.5821_5824dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353960.2:c.5818_5821dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353961.2:c.3463_3466dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006920.6:c.5872_5875dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_148667.2:n.6322_6325dup - 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
SCV003482371	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 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

SCV003482371

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 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, SCV003482371.2

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

Description

Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. This variant disrupts a region of the SCN1A protein in which other variant(s) (p.Arg1988Trp) have been observed in individuals with SCN1A-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1970Asnfs*6) in the SCN1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acid(s) of the SCN1A protein.

#	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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