NM_001330260.2(SCN8A):c.5869_5870insC (p.Lys1957fs) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 6, 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:: RCV001994000.5

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5869_5870insC (p.Lys1957fs)]

NM_001330260.2(SCN8A):c.5869_5870insC (p.Lys1957fs)

Gene:

SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_001330260.2(SCN8A):c.5869_5870insC (p.Lys1957fs)

HGVS:

NC_000012.12:g.51807355_51807356insC
NG_021180.3:g.222398_222399insC
NM_001177984.3:c.5746_5747insC
NM_001330260.2:c.5869_5870insCMANE SELECT
NM_001369788.1:c.5746_5747insC
NM_014191.4:c.5869_5870insC
NP_001171455.1:p.Lys1916fs
NP_001317189.1:p.Lys1957fs
NP_001356717.1:p.Lys1916fs
NP_055006.1:p.Lys1957fs
LRG_1389t1:c.5869_5870insC
LRG_1389t2:c.5869_5870insC
LRG_1389:g.222398_222399insC
LRG_1389p1:p.Lys1957fs
LRG_1389p2:p.Lys1957fs
NC_000012.11:g.52201139_52201140insC

Protein change:

K1916fs

Links:

dbSNP: rs867485612

NCBI 1000 Genomes Browser:

rs867485612

Molecular consequence:

NM_001177984.3:c.5746_5747insC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330260.2:c.5869_5870insC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369788.1:c.5746_5747insC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014191.4:c.5869_5870insC - frameshift variant - [Sequence Ontology: SO:0001589]

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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Profile neighbors for GEO Profiles (Select 60809711) (199)
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Pseudomonas aeruginosa strain CLJ1, whole genome shotgun sequencing project
Pseudomonas aeruginosa strain CLJ1, whole genome shotgun sequencing project
gi|1373670772|gb|PVXJ00000000.1|PVX 0000

Nucleotide
Reservoir_shore_Nov
Reservoir_shore_Nov

biosample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002260496	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 6, 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

SCV002260496

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 6, 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, SCV002260496.3

#	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 results in a frameshift in the SCN8A gene (p.Lys1957Thrfs*41). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the SCN8A protein and extend the protein by 16 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1480700). 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.

#	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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