NM_014191.4(SCN8A):c.630T>G (p.Phe210Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 6, 2024
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:: RCV003590451.2

Allele description [Variation Report for NM_014191.4(SCN8A):c.630T>G (p.Phe210Leu)]

NM_014191.4(SCN8A):c.630T>G (p.Phe210Leu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_014191.4(SCN8A):c.630T>G (p.Phe210Leu)

HGVS:

NC_000012.12:g.51688773T>G
NG_021180.3:g.103816T>G
NM_001177984.3:c.630T>G
NM_001330260.2:c.615-232T>GMANE SELECT
NM_001369788.1:c.615-232T>G
NM_014191.4:c.630T>G
NP_001171455.1:p.Phe210Leu
NP_055006.1:p.Phe210Leu
LRG_1389t1:c.615-232T>G
LRG_1389t2:c.630T>G
LRG_1389:g.103816T>G
LRG_1389p2:p.Phe210Leu
NC_000012.11:g.52082557T>G

Protein change:

F210L

Molecular consequence:

NM_001330260.2:c.615-232T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001369788.1:c.615-232T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001177984.3:c.630T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.630T>G - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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Brevican [Homo sapiens]
Brevican [Homo sapiens]
gi|14318638|gb|AAH09117.1|

Protein
YPL076W (0)
OMIM
hypothetical protein QE343_gp124 [Pseudomonas phage YS35]
hypothetical protein QE343_gp124 [Pseudomonas phage YS35]
gi|2491445260|ref|YP_010764547.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004333363	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 6, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25818041, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004333363

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 6, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC 3rd.

Epilepsia. 2015 May;56(5):707-16. doi: 10.1111/epi.12954. Epub 2015 Mar 25.

PubMed [citation]

PMID:: 25818041

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, SCV004333363.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 210 of the SCN8A protein (p.Phe210Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN8A-related conditions (PMID: 25818041). In at least one individual the variant was observed to be de novo. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN8A protein function. 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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