NM_001165963.4(SCN1A):c.5865A>G (p.Ile1955Met) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 2020
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:: RCV001318625.15

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5865A>G (p.Ile1955Met)]

NM_001165963.4(SCN1A):c.5865A>G (p.Ile1955Met)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.5865A>G (p.Ile1955Met)

Other names:

p.I1955M:ATA>ATG

HGVS:

NC_000002.12:g.165991410T>C
NG_011906.1:g.87230A>G
NM_001165963.4:c.5865A>GMANE SELECT
NM_001165964.3:c.5781A>G
NM_001202435.3:c.5865A>G
NM_001353948.2:c.5865A>G
NM_001353949.2:c.5832A>G
NM_001353950.2:c.5832A>G
NM_001353951.2:c.5832A>G
NM_001353952.2:c.5832A>G
NM_001353954.2:c.5829A>G
NM_001353955.2:c.5829A>G
NM_001353957.2:c.5781A>G
NM_001353958.2:c.5781A>G
NM_001353960.2:c.5778A>G
NM_001353961.2:c.3423A>G
NM_006920.6:c.5832A>G
NP_001159435.1:p.Ile1955Met
NP_001159436.1:p.Ile1927Met
NP_001189364.1:p.Ile1955Met
NP_001340877.1:p.Ile1955Met
NP_001340878.1:p.Ile1944Met
NP_001340879.1:p.Ile1944Met
NP_001340880.1:p.Ile1944Met
NP_001340881.1:p.Ile1944Met
NP_001340883.1:p.Ile1943Met
NP_001340884.1:p.Ile1943Met
NP_001340886.1:p.Ile1927Met
NP_001340887.1:p.Ile1927Met
NP_001340889.1:p.Ile1926Met
NP_001340890.1:p.Ile1141Met
NP_008851.3:p.Ile1944Met
LRG_8:g.87230A>G
NC_000002.11:g.166847920T>C
NM_001165963.1:c.5865A>G
NR_148667.2:n.6282A>G

Protein change:

I1141M

Links:

dbSNP: rs796052952

NCBI 1000 Genomes Browser:

rs796052952

Molecular consequence:

NM_001165963.4:c.5865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5781A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5865A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5832A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5832A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5832A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5832A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5829A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5829A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5781A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5781A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5778A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.3423A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5832A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.6282A>G - 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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kaiC [Synechococcus elongatus PCC 7942 = FACHB-805]
kaiC [Synechococcus elongatus PCC 7942 = FACHB-805]
Gene ID:76399957

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001509337	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 2020)	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

SCV001509337

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 2020)

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, SCV001509337.4

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 206732). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 1955 of the SCN1A protein (p.Ile1955Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine.

#	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: Nov 3, 2024

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