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NM_001110792.2(MECP2):c.418C>T (p.Gln140Ter) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 4, 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:
RCV000698528.8

Allele description [Variation Report for NM_001110792.2(MECP2):c.418C>T (p.Gln140Ter)]

NM_001110792.2(MECP2):c.418C>T (p.Gln140Ter)

Gene:
MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001110792.2(MECP2):c.418C>T (p.Gln140Ter)
Other names:
NM_001110792.2(MECP2):c.418C>T; p.Gln140Ter
HGVS:
  • NC_000023.11:g.154031446G>A
  • NG_007107.3:g.110658C>T
  • NM_001110792.2:c.418C>TMANE SELECT
  • NM_001316337.2:c.103C>T
  • NM_001369391.2:c.103C>T
  • NM_001369392.2:c.103C>T
  • NM_001369393.2:c.103C>T
  • NM_001369394.2:c.103C>T
  • NM_001386137.1:c.-179C>T
  • NM_001386138.1:c.-179C>T
  • NM_001386139.1:c.-179C>T
  • NM_004992.4:c.382C>T
  • NP_001104262.1:p.Gln140Ter
  • NP_001303266.1:p.Gln35Ter
  • NP_001356320.1:p.Gln35Ter
  • NP_001356321.1:p.Gln35Ter
  • NP_001356322.1:p.Gln35Ter
  • NP_001356323.1:p.Gln35Ter
  • NP_004983.1:p.Gln128Ter
  • NP_004983.1:p.Gln128Ter
  • LRG_764t1:c.418C>T
  • LRG_764t2:c.382C>T
  • AJ132917.1:c.382C>T
  • LRG_764:g.110658C>T
  • LRG_764p1:p.Gln140Ter
  • LRG_764p2:p.Gln128Ter
  • NC_000023.10:g.153296897G>A
  • NG_007107.2:g.110682C>T
  • NM_004992.3:c.382C>T
Protein change:
Q128*
Links:
dbSNP: rs267608469
NCBI 1000 Genomes Browser:
rs267608469
Molecular consequence:
  • NM_001386137.1:c.-179C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386138.1:c.-179C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386139.1:c.-179C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001110792.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001316337.2:c.103C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369391.2:c.103C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369392.2:c.103C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369393.2:c.103C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369394.2:c.103C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004992.4:c.382C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Severe neonatal-onset encephalopathy with microcephaly
Synonyms:
Encephalopathy, neonatal severe; Encephalopathy, neonatal severe, due to MECP2 mutations
Identifiers:
MONDO: MONDO:0010397; MedGen: C1968556; Orphanet: 209370; OMIM: 300673

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000827196Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Feb 4, 2022) 		germlineclinical testing

PubMed (9)
[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

Dimensional phenotypic analysis and functional categorisation of mutations reveal novel genotype-phenotype associations in Rett syndrome.

Charman T, Neilson TC, Mash V, Archer H, Gardiner MT, Knudsen GP, McDonnell A, Perry J, Whatley SD, Bunyan DJ, Ravn K, Mount RH, Hastings RP, Hulten M, Orstavik KH, Reilly S, Cass H, Clarke A, Kerr AM, Bailey ME.

Eur J Hum Genet. 2005 Oct;13(10):1121-30.

PubMed [citation]
PMID:
16077736

Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update.

Philippe C, Villard L, De Roux N, Raynaud M, Bonnefond JP, Pasquier L, Lesca G, Mancini J, Jonveaux P, Moncla A, Chelly J, Bienvenu T.

Eur J Med Genet. 2006 Jan-Feb;49(1):9-18.

PubMed [citation]
PMID:
16473305
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000827196.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Gln128*) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 359 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 16077736, 16473305, 22476991). ClinVar contains an entry for this variant (Variation ID: 143553). This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Arg168*) have been determined to be pathogenic (PMID: 10577905, 11058114, 23270700, 24283265, 24511209). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024