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NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 11, 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:
RCV000466020.16

Allele description

NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)

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.952C>T (p.Arg318Cys)
Other names:
p.R306C:CGC>TGC; p.Arg318Cys; NM_001110792.2(MECP2):c.952C>T
HGVS:
  • NC_000023.11:g.154030912G>A
  • NG_007107.3:g.111192C>T
  • NM_001110792.2:c.952C>TMANE SELECT
  • NM_001316337.2:c.637C>T
  • NM_001369391.2:c.637C>T
  • NM_001369392.2:c.637C>T
  • NM_001369393.2:c.637C>T
  • NM_001369394.2:c.637C>T
  • NM_001386137.1:c.247C>T
  • NM_001386138.1:c.247C>T
  • NM_001386139.1:c.247C>T
  • NM_004992.4:c.916C>T
  • NP_001104262.1:p.Arg318Cys
  • NP_001303266.1:p.Arg213Cys
  • NP_001356320.1:p.Arg213Cys
  • NP_001356321.1:p.Arg213Cys
  • NP_001356322.1:p.Arg213Cys
  • NP_001356323.1:p.Arg213Cys
  • NP_001373066.1:p.Arg83Cys
  • NP_001373067.1:p.Arg83Cys
  • NP_001373068.1:p.Arg83Cys
  • NP_004983.1:p.Arg306Cys
  • NP_004983.1:p.Arg306Cys
  • NP_004983.1:p.Arg306Cys
  • LRG_764t1:c.952C>T
  • LRG_764t2:c.916C>T
  • AJ132917.1:c.916C>T
  • LRG_764:g.111192C>T
  • LRG_764p1:p.Arg318Cys
  • LRG_764p2:p.Arg306Cys
  • NC_000023.10:g.153296363G>A
  • NG_007107.2:g.111216C>T
  • NM_001110792.1:c.952C>T
  • NM_004992.3(MECP2):c.916C>T
  • NM_004992.3:c.916C>T
  • NM_004992.4:c.916C>T
  • P51608:p.Arg306Cys
  • g.153296363G>A
  • p.(Arg306Cys)
Protein change:
R213C; ARG306CYS
Links:
UniProtKB: P51608#VAR_010282; OMIM: 300005.0016; dbSNP: rs28935468
NCBI 1000 Genomes Browser:
rs28935468
Molecular consequence:
  • NM_001110792.2:c.952C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001316337.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369391.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369392.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369393.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369394.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386137.1:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386138.1:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386139.1:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function

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
SCV000544613Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 11, 2024) 		germlineclinical testing

PubMed (11)
[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

Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in patients with Rett syndrome.

Obata K, Matsuishi T, Yamashita Y, Fukuda T, Kuwajima K, Horiuchi I, Nagamitsu S, Iwanaga R, Kimura A, Omori I, Endo S, Mori K, Kondo I.

J Med Genet. 2000 Aug;37(8):608-10. No abstract available.

PubMed [citation]
PMID:
10991688
PMCID:
PMC1734655

A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients.

Bourdon V, Philippe C, Labrune O, Amsallem D, Arnould C, Jonveaux P.

Hum Genet. 2001 Jan;108(1):43-50.

PubMed [citation]
PMID:
11214906
See all PubMed Citations (11)

Details of each submission

From Invitae, SCV000544613.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the MECP2 protein (p.Arg306Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Rett syndrome (RTT) and accounts for approximately 5% of all classical RTT cases (PMID: 10991688, 11214906, 14649554, 16473305, 24511209). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11824). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MECP2 protein function. Experimental studies have shown that this missense change affects MECP2 function (PMID: 23770565, 23770587, 24970834, 26647311). This variant disrupts the p.Arg306 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10767337, 14649554, 16473305). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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 16, 2024