NM_001330260.2(SCN8A):c.5579_5599dup (p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 24, 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:: RCV001378321.10

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5579_5599dup (p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg)]

NM_001330260.2(SCN8A):c.5579_5599dup (p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_001330260.2(SCN8A):c.5579_5599dup (p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg)

HGVS:

NC_000012.12:g.51807065_51807085dup
NG_021180.3:g.222108_222128dup
NM_001177984.3:c.5456_5476dup
NM_001330260.2:c.5579_5599dupMANE SELECT
NM_001369788.1:c.5456_5476dup
NM_014191.4:c.5579_5599dup
NP_001171455.1:p.Arg1825_Gln1826insArgGluLeuAspIleLeuArg
NP_001317189.1:p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg
NP_001356717.1:p.Arg1825_Gln1826insArgGluLeuAspIleLeuArg
NP_055006.1:p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg
LRG_1389t1:c.5579_5599dup
LRG_1389t2:c.5579_5599dup
LRG_1389:g.222108_222128dup
LRG_1389p1:p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg
LRG_1389p2:p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg
NC_000012.11:g.52200848_52200849insGGGAGTTGGACATCCTGCGGC
NC_000012.11:g.52200849_52200869dup

Links:

dbSNP: rs2138944020

NCBI 1000 Genomes Browser:

rs2138944020

Molecular consequence:

NM_001177984.3:c.5456_5476dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001330260.2:c.5579_5599dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001369788.1:c.5456_5476dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_014191.4:c.5579_5599dup - inframe_insertion - [Sequence Ontology: SO:0001821]

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
SCV001575866	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 24, 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

SCV001575866

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 24, 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, SCV001575866.5

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1067137). This variant has been observed in individual(s) with clinical features of SCN8A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.5579_5599dup, results in the insertion of 7 amino acid(s) of the SCN8A protein (p.Arg1866_Gln1867insArgGluLeuAspIleLeuArg), but otherwise preserves the integrity of the reading frame.

#	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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