NM_001110792.2(MECP2):c.940C>T (p.Pro314Ser) AND none provided

Clinical significance:Likely pathogenic (Last evaluated: Jan 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001286649.2

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

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

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.940C>T (p.Pro314Ser)
HGVS:
  • 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_004992.3:c.904C>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
Protein change:
P209S
Links:
dbSNP: rs61751373
NCBI 1000 Genomes Browser:
rs61751373
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_004992.3:c.904C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.904C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001473257ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Jan 30, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001473257.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MECP2 c.904C>T; p.Pro302Ser variant (rs61751373) is reported in the literature an individual with classical Rett syndrome (Zahorakova 2007). Additionally, other amino acid substitutions at this codon (p.Pro302Leu, p.Pro302Ala, p.Pro302Arg, p.Pro302His, p.Pro302Thr) have been reported in individuals with Rett syndrome (see link to RettBASE and references therein). The c.904C>T; p.Pro302Ser is reported in the ClinVar database (Variation ID: 143735) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 302 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, this amino acid has been implicated in binding a co-repressor complex and one variant at this position, p.Pro302Arg, abolishes this interaction (Lyst 2013). Considering available information, this variant is classified as likely pathogenic. References: RettBASE: http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic Zahorakova D et al. Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms. J Hum Genet. 2007;52(4):342-8.

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

Last Updated: Nov 11, 2021

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