NM_001165963.4(SCN1A):c.3620T>C (p.Leu1207Pro) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV000818870.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3620T>C (p.Leu1207Pro)]

NM_001165963.4(SCN1A):c.3620T>C (p.Leu1207Pro)

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.3620T>C (p.Leu1207Pro)

HGVS:

NC_000002.12:g.166013829A>G
NG_011906.1:g.64811T>C
NM_001165963.4:c.3620T>CMANE SELECT
NM_001165964.3:c.3536T>C
NM_001202435.3:c.3620T>C
NM_001353948.2:c.3620T>C
NM_001353949.2:c.3587T>C
NM_001353950.2:c.3587T>C
NM_001353951.2:c.3587T>C
NM_001353952.2:c.3587T>C
NM_001353954.2:c.3584T>C
NM_001353955.2:c.3584T>C
NM_001353957.2:c.3536T>C
NM_001353958.2:c.3536T>C
NM_001353960.2:c.3533T>C
NM_001353961.2:c.1178T>C
NM_006920.6:c.3587T>C
NP_001159435.1:p.Leu1207Pro
NP_001159436.1:p.Leu1179Pro
NP_001189364.1:p.Leu1207Pro
NP_001340877.1:p.Leu1207Pro
NP_001340878.1:p.Leu1196Pro
NP_001340879.1:p.Leu1196Pro
NP_001340880.1:p.Leu1196Pro
NP_001340881.1:p.Leu1196Pro
NP_001340883.1:p.Leu1195Pro
NP_001340884.1:p.Leu1195Pro
NP_001340886.1:p.Leu1179Pro
NP_001340887.1:p.Leu1179Pro
NP_001340889.1:p.Leu1178Pro
NP_001340890.1:p.Leu393Pro
NP_008851.3:p.Leu1196Pro
LRG_8t1:c.3587T>C
LRG_8:g.64811T>C
NC_000002.11:g.166870339A>G
NM_001165963.1:c.3620T>C
NM_006920.4:c.3587T>C
NR_148667.2:n.3973T>C

Protein change:

L1178P

Links:

UniProtKB/Swiss-Prot: VAR_043360; dbSNP: rs121917963

NCBI 1000 Genomes Browser:

rs121917963

Molecular consequence:

NM_001165963.4:c.3620T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.3536T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.3620T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.3620T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.3584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.3584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.3536T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.3536T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.3533T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.1178T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.3973T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000959506	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18413471, 30945278, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959506

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 17, 2020)

germline

clinical testing

PubMed (3)
[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

Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified.

Zucca C, Redaelli F, Epifanio R, Zanotta N, Romeo A, Lodi M, Veggiotti P, Airoldi G, Panzeri C, Romaniello R, De Polo G, Bonanni P, Cardinali S, Baschirotto C, Martorell L, Borgatti R, Bresolin N, Bassi MT.

Arch Neurol. 2008 Apr;65(4):489-94. doi: 10.1001/archneur.65.4.489.

PubMed [citation]

PMID:: 18413471

The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.

Jiao Q, Sun H, Zhang H, Wang R, Li S, Sun D, Yang XA, Jin Y.

Clin Genet. 2019 Aug;96(2):140-150. doi: 10.1111/cge.13548. Epub 2019 Apr 22.

PubMed [citation]

PMID:: 30945278

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959506.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 1207 of the SCN1A protein (p.Leu1207Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 18413471, 30945278, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68530). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.

#	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: Oct 20, 2024

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