NM_001110792.2(MECP2):c.940C>T (p.Pro314Ser) AND Severe neonatal-onset encephalopathy with microcephaly

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001110792.2(MECP2):c.940C>T (p.Pro314Ser)]

NM_001110792.2(MECP2):c.940C>T (p.Pro314Ser)

MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001110792.2(MECP2):c.940C>T (p.Pro314Ser)
  • NC_000023.11:g.154030924G>A
  • NG_007107.2:g.111204C>T
  • NG_007107.3:g.111180C>T
  • NM_001110792.2:c.940C>TMANE SELECT
  • NM_001316337.2:c.625C>T
  • NM_001369391.2:c.625C>T
  • NM_001369392.2:c.625C>T
  • NM_001369393.2:c.625C>T
  • NM_001369394.2:c.625C>T
  • NM_001386137.1:c.235C>T
  • NM_001386138.1:c.235C>T
  • NM_001386139.1:c.235C>T
  • NM_004992.4:c.904C>T
  • NP_001104262.1:p.Pro314Ser
  • NP_001303266.1:p.Pro209Ser
  • NP_001356320.1:p.Pro209Ser
  • NP_001356321.1:p.Pro209Ser
  • NP_001356322.1:p.Pro209Ser
  • NP_001356323.1:p.Pro209Ser
  • NP_001373066.1:p.Pro79Ser
  • NP_001373067.1:p.Pro79Ser
  • NP_001373068.1:p.Pro79Ser
  • NP_004983.1:p.Pro302Ser
  • NP_004983.1:p.Pro302Ser
  • LRG_764t1:c.940C>T
  • LRG_764t2:c.904C>T
  • AJ132917.1:c.904C>T
  • LRG_764:g.111180C>T
  • LRG_764p1:p.Pro314Ser
  • LRG_764p2:p.Pro302Ser
  • NC_000023.10:g.153296375G>A
  • NM_004992.3:c.904C>T
Protein change:
dbSNP: rs61751373
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001110792.2:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001316337.2:c.625C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369391.2:c.625C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369392.2:c.625C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369393.2:c.625C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369394.2:c.625C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386137.1:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386138.1:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386139.1:c.235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.904C>T - missense variant - [Sequence Ontology: SO:0001583]


Severe neonatal-onset encephalopathy with microcephaly
Encephalopathy, neonatal severe; Encephalopathy, neonatal severe, due to MECP2 mutations
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)
SCV001232654Invitaecriteria provided, single submitter
(Jan 15, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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



Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms.

Zahorakova D, Rosipal R, Hadac J, Zumrova A, Bzduch V, Misovicova N, Baxova A, Zeman J, Martasek P.

J Hum Genet. 2007;52(4):342-348. doi: 10.1007/s10038-007-0121-x. Epub 2007 Feb 15.

PubMed [citation]

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]
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001232654.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


This sequence change replaces proline with serine at codon 302 of the MECP2 protein (p.Pro302Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Rett syndrome (PMID: 17387578), and has also been observed to be de novo in an individual affected with clinical features of MECP2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 143735). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Pro302 amino acid residue in MECP2. Other variants that disrupt this residue have been observed in individuals with MECP2-related conditions (PMID: 10767337, 10814718, 10814719, 15737703), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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