NM_001330260.2(SCN8A):c.5307C>A (p.Phe1769Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 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:: RCV003588872.2

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5307C>A (p.Phe1769Leu)]

NM_001330260.2(SCN8A):c.5307C>A (p.Phe1769Leu)

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_001330260.2(SCN8A):c.5307C>A (p.Phe1769Leu)

HGVS:

NC_000012.12:g.51806793C>A
NG_021180.3:g.221836C>A
NM_001177984.3:c.5184C>A
NM_001330260.2:c.5307C>AMANE SELECT
NM_001369788.1:c.5184C>A
NM_014191.4:c.5307C>A
NP_001171455.1:p.Phe1728Leu
NP_001317189.1:p.Phe1769Leu
NP_001356717.1:p.Phe1728Leu
NP_055006.1:p.Phe1769Leu
LRG_1389t1:c.5307C>A
LRG_1389t2:c.5307C>A
LRG_1389:g.221836C>A
LRG_1389p1:p.Phe1769Leu
LRG_1389p2:p.Phe1769Leu
NC_000012.11:g.52200577C>A

Protein change:

F1728L

Molecular consequence:

NM_001177984.3:c.5184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.5307C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.5184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.5307C>A - 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

Clear Turn Off Turn On

At.28347 AND (alive[prop]) (2)
Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004307325	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 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

SCV004307325

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 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, SCV004307325.1

#	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 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 sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1769 of the SCN8A protein (p.Phe1769Leu). 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: 2441961). 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.

#	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

ClinVar

Relating variation to medicine