U.S. flag

An official website of the United States government

NM_001110792.2(MECP2):c.1243_*586del (p.Pro415fs) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 2023
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:
RCV003524072.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.1243_*586del (p.Pro415fs)]

NM_001110792.2(MECP2):c.1243_*586del (p.Pro415fs)

Gene:
MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001110792.2(MECP2):c.1243_*586del (p.Pro415fs)
HGVS:
  • NC_000023.11:g.154029791_154030631del
  • NG_007107.3:g.111483_112323del
  • NM_001110792.2:c.1243_*586delMANE SELECT
  • NM_001316337.2:c.928_*586del
  • NM_001369391.2:c.928_*586del
  • NM_001369392.2:c.928_*586del
  • NM_001369393.2:c.928_*586del
  • NM_001369394.2:c.928_*586del
  • NM_001386137.1:c.538_*586del
  • NM_001386138.1:c.538_*586del
  • NM_001386139.1:c.538_*586del
  • NM_004992.4:c.1207_*586del
  • NP_001104262.1:p.Pro415fs
  • NP_001303266.1:p.Pro310fs
  • NP_001356320.1:p.Pro310fs
  • NP_001356321.1:p.Pro310fs
  • NP_001356322.1:p.Pro310fs
  • NP_001356323.1:p.Pro310fs
  • NP_001373066.1:p.Pro180fs
  • NP_001373067.1:p.Pro180fs
  • NP_001373068.1:p.Pro180fs
  • NP_004983.1:p.Pro403fs
  • LRG_764t1:c.1243_*586del
  • LRG_764t2:c.1207_*586del
  • LRG_764:g.111483_112323del
  • LRG_764p1:p.Pro415fs
  • LRG_764p2:p.Pro403fs
  • NC_000023.10:g.153295232_153296072del
  • NC_000023.10:g.153295242_153296082del
Protein change:
P180fs
Molecular consequence:
  • NM_001110792.2:c.1243_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001316337.2:c.928_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001369391.2:c.928_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001369392.2:c.928_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001369393.2:c.928_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001369394.2:c.928_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386137.1:c.538_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386138.1:c.538_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386139.1:c.538_*586del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004992.4:c.1207_*586del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004365670Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 21, 2023) 		germlineclinical testing

PubMed (4)
[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

A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males.

Meloni I, Bruttini M, Longo I, Mari F, Rizzolio F, D'Adamo P, Denvriendt K, Fryns JP, Toniolo D, Renieri A.

Am J Hum Genet. 2000 Oct;67(4):982-5. Epub 2000 Sep 12.

PubMed [citation]
PMID:
10986043
PMCID:
PMC1287900

MECP2 analysis in mentally retarded patients: implications for routine DNA diagnostics.

Kleefstra T, Yntema HG, Nillesen WM, Oudakker AR, Mullaart RA, Geerdink N, van Bokhoven H, de Vries BB, Sistermans EA, Hamel BC.

Eur J Hum Genet. 2004 Jan;12(1):24-8.

PubMed [citation]
PMID:
14560307
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004365670.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Pro403Asnfs*35) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 84 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Gln406*) have been determined to be pathogenic (PMID: 10986043, 14560307, 22476991). 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