NM_001165963.4(SCN1A):c.335C>T (p.Thr112Ile) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 18, 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:
RCV001854244.5

Allele description [Variation Report for NM_001165963.4(SCN1A):c.335C>T (p.Thr112Ile)]

NM_001165963.4(SCN1A):c.335C>T (p.Thr112Ile)

Gene:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.335C>T (p.Thr112Ile)
HGVS:
  • NC_000002.12:g.166058618G>A
  • NG_011906.1:g.20022C>T
  • NM_001165963.4:c.335C>TMANE SELECT
  • NM_001165964.3:c.335C>T
  • NM_001202435.3:c.335C>T
  • NM_001353948.2:c.335C>T
  • NM_001353949.2:c.335C>T
  • NM_001353950.2:c.335C>T
  • NM_001353951.2:c.335C>T
  • NM_001353952.2:c.335C>T
  • NM_001353954.2:c.335C>T
  • NM_001353955.2:c.335C>T
  • NM_001353957.2:c.335C>T
  • NM_001353958.2:c.335C>T
  • NM_001353960.2:c.335C>T
  • NM_001353961.2:c.-2091C>T
  • NM_006920.6:c.335C>T
  • NP_001159435.1:p.Thr112Ile
  • NP_001159436.1:p.Thr112Ile
  • NP_001189364.1:p.Thr112Ile
  • NP_001340877.1:p.Thr112Ile
  • NP_001340878.1:p.Thr112Ile
  • NP_001340879.1:p.Thr112Ile
  • NP_001340880.1:p.Thr112Ile
  • NP_001340881.1:p.Thr112Ile
  • NP_001340883.1:p.Thr112Ile
  • NP_001340884.1:p.Thr112Ile
  • NP_001340886.1:p.Thr112Ile
  • NP_001340887.1:p.Thr112Ile
  • NP_001340889.1:p.Thr112Ile
  • NP_008851.3:p.Thr112Ile
  • LRG_8t1:c.335C>T
  • LRG_8:g.20022C>T
  • NC_000002.11:g.166915128G>A
  • NM_006920.4:c.335C>T
  • NR_148667.2:n.721C>T
  • P35498:p.Thr112Ile
Protein change:
T112I
Links:
UniProtKB: P35498#VAR_029663; UniProtKB/Swiss-Prot: VAR_029663; dbSNP: rs121918745
NCBI 1000 Genomes Browser:
rs121918745
Molecular consequence:
  • NM_001353961.2:c.-2091C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001165963.4:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.721C>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002248198Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 18, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures.

Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, Hara K, Morikawa T, Yagi K, Yamakawa K, Inoue Y.

Brain. 2003 Mar;126(Pt 3):531-46.

PubMed [citation]
PMID:
12566275

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, SCV002248198.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

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. 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) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 68615). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 12566275; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 112 of the SCN1A protein (p.Thr112Ile).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024