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NM_001110792.2(MECP2):c.504C>G (p.Asp168Glu) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 10, 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:
RCV000815972.14

Allele description

NM_001110792.2(MECP2):c.504C>G (p.Asp168Glu)

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.504C>G (p.Asp168Glu)
Other names:
p.D156E:GAC>GAG; NM_001110792.2(MECP2):c.504C>G; p.Asp168Glu
HGVS:
  • NC_000023.11:g.154031360G>C
  • NG_007107.3:g.110744C>G
  • NM_001110792.2:c.504C>GMANE SELECT
  • NM_001316337.2:c.189C>G
  • NM_001369391.2:c.189C>G
  • NM_001369392.2:c.189C>G
  • NM_001369393.2:c.189C>G
  • NM_001369394.2:c.189C>G
  • NM_001386137.1:c.-129+36C>G
  • NM_001386138.1:c.-129+36C>G
  • NM_001386139.1:c.-129+36C>G
  • NM_004992.4:c.468C>G
  • NP_001104262.1:p.Asp168Glu
  • NP_001303266.1:p.Asp63Glu
  • NP_001356320.1:p.Asp63Glu
  • NP_001356321.1:p.Asp63Glu
  • NP_001356322.1:p.Asp63Glu
  • NP_001356323.1:p.Asp63Glu
  • NP_004983.1:p.Asp156Glu
  • NP_004983.1:p.Asp156Glu
  • LRG_764t1:c.504C>G
  • LRG_764t2:c.468C>G
  • AJ132917.1:c.468C>G
  • LRG_764:g.110744C>G
  • LRG_764p1:p.Asp168Glu
  • LRG_764p2:p.Asp156Glu
  • NC_000023.10:g.153296811G>C
  • NG_007107.2:g.110768C>G
  • NM_001110792.2:c.504C>G
  • NM_004992.3:c.468C>G
Protein change:
D156E
Links:
dbSNP: rs61748408
NCBI 1000 Genomes Browser:
rs61748408
Molecular consequence:
  • NM_001386137.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386138.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386139.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001110792.2:c.504C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001316337.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369391.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369392.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369393.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369394.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.468C>G - missense variant - [Sequence Ontology: SO:0001583]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000956455Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Aug 10, 2023)
germlineclinical testing

PubMed (14)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation.

Yamada Y, Miura K, Kumagai T, Hayakawa C, Miyazaki S, Matsumoto A, Kurosawa K, Nomura N, Taniguchi H, Sonta SI, Yamanaka T, Wakamatsu N.

Hum Mutat. 2001 Sep;18(3):253.

PubMed [citation]
PMID:
11524741

Influence of mutation type and location on phenotype in 123 patients with Rett syndrome.

Huppke P, Held M, Hanefeld F, Engel W, Laccone F.

Neuropediatrics. 2002 Apr;33(2):63-8.

PubMed [citation]
PMID:
12075485
See all PubMed Citations (14)

Details of each submission

From Invitae, SCV000956455.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 156 of the MECP2 protein (p.Asp156Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Rett syndrome (PMID: 11524741, 12075485, 15737703, 16473305, 16672765, 19722030, 22182064, 26984561, 27354166). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 95196). 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 MECP2 protein function. Experimental studies have shown that this missense change affects MECP2 function (PMID: 12843318, 26418480). This variant disrupts the p.Asp156 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been observed in individuals with MECP2-related conditions (PMID: 11309679, 15737703, 18021529, 22182064), which suggests that this may be a clinically significant amino acid residue. 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 16, 2024