NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe) AND Focal cortical dysplasia type II

Clinical significance:Pathogenic (Last evaluated: Sep 16, 2020)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000477713.5

Allele description [Variation Report for NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe)]

NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe)

Gene:
MTOR:mechanistic target of rapamycin kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.22
Genomic location:
Preferred name:
NM_004958.4(MTOR):c.6644C>T (p.Ser2215Phe)
Other names:
NM_004958.3(MTOR):c.6644C>T; p.Ser2215Phe
HGVS:
  • NC_000001.11:g.11124516G>A
  • NG_033239.1:g.143036C>T
  • NM_004958.4:c.6644C>TMANE SELECT
  • NP_004949.1:p.Ser2215Phe
  • LRG_734t1:c.6644C>T
  • LRG_734:g.143036C>T
  • NC_000001.10:g.11184573G>A
  • NM_004958.3:c.6644C>T
Protein change:
S2215F; SER2215PHE
Links:
OMIM: 601231.0008; dbSNP: rs587777894
NCBI 1000 Genomes Browser:
rs587777894
Molecular consequence:
  • NM_004958.4:c.6644C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Focal cortical dysplasia type II (FCORD2)
Synonyms:
Focal cortical dysplasia of Taylor; Cortical dysplasia of Taylor; Focal cortical dysplasia type 2
Identifiers:
MONDO: MONDO:0011818; MedGen: C1846385; OMIM: 607341; Human Phenotype Ontology: HP:0032051

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000564176OMIMno assertion criteria providedPathogenic
(Sep 16, 2020)
somaticliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy.

Møller RS, Weckhuysen S, Chipaux M, Marsan E, Taly V, Bebin EM, Hiatt SM, Prokop JW, Bowling KM, Mei D, Conti V, de la Grange P, Ferrand-Sorbets S, Dorfmüller G, Lambrecq V, Larsen LH, Leguern E, Guerrini R, Rubboli G, Cooper GM, Baulac S.

Neurol Genet. 2016 Dec;2(6):e118.

PubMed [citation]
PMID:
27830187
PMCID:
PMC5089441

Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

Mirzaa GM, Campbell CD, Solovieff N, Goold C, Jansen LA, Menon S, Timms AE, Conti V, Biag JD, Adams C, Boyle EA, Collins S, Ishak G, Poliachik S, Girisha KM, Yeung KS, Chung BHY, Rahikkala E, Gunter SA, McDaniel SS, Macmurdo CF, Bernstein JA, et al.

JAMA Neurol. 2016 Jul 1;73(7):836-845. doi: 10.1001/jamaneurol.2016.0363.

PubMed [citation]
PMID:
27159400
PMCID:
PMC4979321

Details of each submission

From OMIM, SCV000564176.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In resected brain tissue from 3 unrelated French patients with seizures due to focal cortical dysplasia type II (FCORD2; 607341), Moller et al. (2016) identified a somatic c.6644C-T transition (c.6644C-T, NM_004958.3) in the MTOR gene, resulting in a ser2215-to-phe (S2215F) substitution in the kinase domain. The mutations, which were found by deep sequencing of a targeted gene panel, were not found in patient blood. The S2215F variant was not found in the ExAC database. The mutant allele frequency was low, ranging from about 1 to 7%. Functional studies of the variant were not performed, although patient dysmorphic neurons showed intense S6 phosphorylation, consistent with hyperactivation of the mTOR pathway.

Mirzaa et al. (2016) reported 2 additional patients with focal cortical dysplasia and seizures in whom the S2215F mutation was absent in saliva but present in brain, at alternative allele fractions of 0.055 in one and 0.012-0.086 in the other.

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

Last Updated: Nov 27, 2021

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