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NM_001165963.4(SCN1A):c.5066T>C (p.Met1689Thr) AND Early infantile epileptic encephalopathy with suppression bursts

Clinical significance:Uncertain significance (Last evaluated: Sep 1, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

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Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001216747.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5066T>C (p.Met1689Thr)]

NM_001165963.4(SCN1A):c.5066T>C (p.Met1689Thr)

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.5066T>C (p.Met1689Thr)
HGVS:
  • NC_000002.12:g.165992209A>G
  • NG_011906.1:g.86431T>C
  • NM_001165963.4:c.5066T>CMANE SELECT
  • NM_001165964.3:c.4982T>C
  • NM_001202435.3:c.5066T>C
  • NM_001353948.2:c.5066T>C
  • NM_001353949.2:c.5033T>C
  • NM_001353950.2:c.5033T>C
  • NM_001353951.2:c.5033T>C
  • NM_001353952.2:c.5033T>C
  • NM_001353954.2:c.5030T>C
  • NM_001353955.2:c.5030T>C
  • NM_001353957.2:c.4982T>C
  • NM_001353958.2:c.4982T>C
  • NM_001353960.2:c.4979T>C
  • NM_001353961.2:c.2624T>C
  • NM_006920.6:c.5033T>C
  • NP_001159435.1:p.Met1689Thr
  • NP_001159436.1:p.Met1661Thr
  • NP_001189364.1:p.Met1689Thr
  • NP_001340877.1:p.Met1689Thr
  • NP_001340878.1:p.Met1678Thr
  • NP_001340879.1:p.Met1678Thr
  • NP_001340880.1:p.Met1678Thr
  • NP_001340881.1:p.Met1678Thr
  • NP_001340883.1:p.Met1677Thr
  • NP_001340884.1:p.Met1677Thr
  • NP_001340886.1:p.Met1661Thr
  • NP_001340887.1:p.Met1661Thr
  • NP_001340889.1:p.Met1660Thr
  • NP_001340890.1:p.Met875Thr
  • NP_008851.3:p.Met1678Thr
  • LRG_8:g.86431T>C
  • NC_000002.11:g.166848719A>G
  • NM_001165963.1:c.5066T>C
  • NM_001165963.2:c.5066T>C
  • NR_148667.2:n.5483T>C
Protein change:
M1660T
Links:
Molecular consequence:
  • NM_001165963.4:c.5066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4982T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.5066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.5066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.5033T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.5033T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.5033T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.5033T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.5030T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.5030T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4982T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4982T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4979T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.2624T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.5033T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.5483T>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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001388559Invitaecriteria provided, single submitter
Uncertain significance
(Sep 1, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

Help
EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001388559.4

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

Description

This sequence change replaces methionine with threonine at codon 1689 of the SCN1A protein (p.Met1689Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. 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. 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.

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

Last Updated: Feb 7, 2023