U.S. flag

An official website of the United States government

NM_001110792.2(MECP2):c.437C>G (p.Ser146Cys) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 8, 2024
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:
RCV000698431.10

Allele description [Variation Report for NM_001110792.2(MECP2):c.437C>G (p.Ser146Cys)]

NM_001110792.2(MECP2):c.437C>G (p.Ser146Cys)

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.437C>G (p.Ser146Cys)
Other names:
NM_001110792.2(MECP2):c.437C>G; p.Ser146Cys
HGVS:
  • NC_000023.11:g.154031427G>C
  • NG_007107.3:g.110677C>G
  • NM_001110792.2:c.437C>GMANE SELECT
  • NM_001316337.2:c.122C>G
  • NM_001369391.2:c.122C>G
  • NM_001369392.2:c.122C>G
  • NM_001369393.2:c.122C>G
  • NM_001369394.2:c.122C>G
  • NM_001386137.1:c.-160C>G
  • NM_001386138.1:c.-160C>G
  • NM_001386139.1:c.-160C>G
  • NM_004992.4:c.401C>G
  • NP_001104262.1:p.Ser146Cys
  • NP_001303266.1:p.Ser41Cys
  • NP_001356320.1:p.Ser41Cys
  • NP_001356321.1:p.Ser41Cys
  • NP_001356322.1:p.Ser41Cys
  • NP_001356323.1:p.Ser41Cys
  • NP_004983.1:p.Ser134Cys
  • NP_004983.1:p.Ser134Cys
  • LRG_764t1:c.437C>G
  • LRG_764t2:c.401C>G
  • AJ132917.1:c.401C>G
  • LRG_764:g.110677C>G
  • LRG_764p1:p.Ser146Cys
  • LRG_764p2:p.Ser134Cys
  • NC_000023.10:g.153296878G>C
  • NG_007107.2:g.110701C>G
  • NM_004992.3:c.401C>G
  • NM_004992.4:c.401C>G
  • P51608:p.Ser134Cys
Protein change:
S134C
Links:
UniProtKB: P51608#VAR_010278; dbSNP: rs61748390
NCBI 1000 Genomes Browser:
rs61748390
Molecular consequence:
  • NM_001386137.1:c.-160C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386138.1:c.-160C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386139.1:c.-160C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001110792.2:c.437C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001316337.2:c.122C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369391.2:c.122C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369392.2:c.122C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369393.2:c.122C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369394.2:c.122C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.401C>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

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
SCV000827093Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 8, 2024) 		germlineclinical testing

PubMed (12)
[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

Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.

Cheadle JP, Gill H, Fleming N, Maynard J, Kerr A, Leonard H, Krawczak M, Cooper DN, Lynch S, Thomas N, Hughes H, Hulten M, Ravine D, Sampson JR, Clarke A.

Hum Mol Genet. 2000 Apr 12;9(7):1119-29. Erratum in: Hum Mol Genet 2000 Jul 1;9(11):1717.

PubMed [citation]
PMID:
10767337

Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients.

Huppke P, Laccone F, Krämer N, Engel W, Hanefeld F.

Hum Mol Genet. 2000 May 22;9(9):1369-75.

PubMed [citation]
PMID:
10814718
See all PubMed Citations (12)

Details of each submission

From Invitae, SCV000827093.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 134 of the MECP2 protein (p.Ser134Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Rett syndrome (PMID: 10767337, 10814718, 11738864, 11738883, 12655490, 17089071, 18337588, 21160487, 22182064, 23696494). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 143562). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects MECP2 function (PMID: 26418480). 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: May 7, 2024