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

This record was updated by the submitter. Please see the current version.

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000956455	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 11524741, 12075485, 16473305, 16672765, 19722030, 26984561, 27354166, 12843318, 26418480, 11309679, 15737703, 18021529, 22182064, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000956455

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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