ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp)
Variation ID: 11814 Accession: VCV000011814.65
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154032268 (GRCh38) [ NCBI UCSC ] X: 153297719 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 24, 2015 Apr 15, 2024 Jan 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.352C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Arg118Trp missense NM_004992.4:c.316C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Arg106Trp missense NM_001316337.2:c.37C>T NP_001303266.1:p.Arg13Trp missense NM_001369391.2:c.37C>T NP_001356320.1:p.Arg13Trp missense NM_001369392.2:c.37C>T NP_001356321.1:p.Arg13Trp missense NM_001369393.2:c.37C>T NP_001356322.1:p.Arg13Trp missense NM_001369394.2:c.37C>T NP_001356323.1:p.Arg13Trp missense NM_001386137.1:c.-245C>T 5 prime UTR NM_001386138.1:c.-245C>T 5 prime UTR NM_001386139.1:c.-245C>T 5 prime UTR NC_000023.11:g.154032268G>A NC_000023.10:g.153297719G>A NG_007107.3:g.109836C>T LRG_764:g.109836C>T LRG_764t1:c.352C>T LRG_764p1:p.Arg118Trp LRG_764t2:c.316C>T LRG_764p2:p.Arg106Trp P51608:p.Arg106Trp AJ132917.1:c.316C>T - Protein change
- R106W, R118W, R13W
- Other names
- NM_001110792.2(MECP2):c.352C>T
- p.Arg118Trp
- Canonical SPDI
- NC_000023.11:154032267:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MECP2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1824 | 2145 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (14) |
criteria provided, multiple submitters, no conflicts
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Dec 11, 2023 | RCV000012585.58 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 7, 2022 | RCV000255874.33 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 15, 2024 | RCV000552837.17 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2016 | RCV001195924.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 25, 2019 | RCV001000318.15 | |
Pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV002247329.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 26, 2019 | RCV002311513.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV003224092.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000247964.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Likely pathogenic
(Jul 14, 2015)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
unknown
|
Molecular Diagnostics Lab, Nemours Children's Health, Delaware
Accession: SCV000537188.1
First in ClinVar: Aug 22, 2016 Last updated: Aug 22, 2016 |
Comment:
Microcephaly; Developmental delay; Seizures; Frequent hand to face movements
Number of individuals with the variant: 1
Age: 10-19 years
Sex: female
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Pathogenic
(Mar 01, 2018)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Undiagnosed Diseases Network, NIH
Study: Undiagnosed Diseases Network (NIH), UDN
Accession: SCV000837693.1 First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018 |
Number of individuals with the variant: 1
Clinical Features:
Torticollis (present) , Strabismus (present) , Stereotypy (present) , Seizures (present) , Repetitive compulsive behavior (present) , Reduced tendon reflexes (present) , Prolonged neonatal jaundice … (more)
Torticollis (present) , Strabismus (present) , Stereotypy (present) , Seizures (present) , Repetitive compulsive behavior (present) , Reduced tendon reflexes (present) , Prolonged neonatal jaundice (present) , Premature delivery because of cervical insufficiency or membrane fragility (present) , Premature birth (present) , Obstructive sleep apnea syndrome (present) , Obesity (present) , Myopia (present) , Low-set ears (present) , Laryngomalacia (present) , Head-banging (present) , Global developmental delay (present) , Generalized hypotonia (present) , EEG with generalized slow activity (present) , Dysphagia (present) , Diffuse cerebral atrophy (present) , Developmental regression (present) , Chronic constipation (present) , Cerebellar atrophy (present) , Bruxism (present) , Aspiration (present) , Abdominal pain (present) , Abdominal distention (present) (less)
Age: 0-9 years
Sex: female
Ethnicity/Population group: White
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Pathogenic
(Mar 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000229062.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919615.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
Comment:
Variant summary: MECP2 c.316C>T (p.Arg106Trp) results in a non-conservative amino acid change located in the Methyl-CpG DNA binding of the encoded protein sequence. Five of … (more)
Variant summary: MECP2 c.316C>T (p.Arg106Trp) results in a non-conservative amino acid change located in the Methyl-CpG DNA binding of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. A functional study, Yusufzai_2000, found the variant to abolish selectivity for methylated DNA binding. The variant was absent in 87536 control chromosomes (ExAC). The variant, c.316C>T, has been reported in the literature in multiple individuals affected with Rett Syndrome (Wan_1999, Cheadle_2000, Buyse_2000, Vacca_2001, and Zahorakova_2007). These data indicate that the variant is very likely to be associated with disease. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely pathogenic/pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149830.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: female
Tissue: blood
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Pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Autism, susceptibility to, X-linked 3
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366348.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM1,PM2,PP3.
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Pathogenic
(Aug 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV002034761.1
First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
Comment:
The MECP2 c.352C>T (p.Arg118Trp) missense variant, also noted as p.Arg106Trp in the literature, is a common pathogenic variant and accounts for 2.79% of cases as … (more)
The MECP2 c.352C>T (p.Arg118Trp) missense variant, also noted as p.Arg106Trp in the literature, is a common pathogenic variant and accounts for 2.79% of cases as per RettBASE (Christodoulou et al. 2003). Across a selection of the available literature, the p.Arg118Trp variant has been reported in a heterozygous state in at least 20 unrelated individuals affected with Rett syndrome, and the variant is typically associated with early onset disorder (Amir et al. 1999; Bebbington et al. 2008; Khalili et al. 2020). The variant is not found in version 2.1.1 or version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequence coverage, which suggest the variant is rare. The Arg118 residue is located in the critical methyl-CpG binding domain and is shown to result in significantly reduced chromatin binding and decreased MECP2 accumulation at chromocenters compared to wildtype (Agarwal et al. 2011; Sheikh et al. 2016). Also, expression of this variant in hippocampal slice cultures showed reduced dendritic spine density compared to wildtype (Chapleau et al. 2009). This variant was identified in a de novo state. Based on the available evidence, the p.Arg118Trp variant is classified as pathogenic for Rett syndrome. (less)
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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X-linked intellectual disability-psychosis-macroorchidism syndrome
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002517602.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Mar 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000845974.4
First in ClinVar: Nov 08, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.R106W pathogenic mutation (also known as c.316C>T and 390C>T), located in coding exon 2 of the MECP2 gene, results from a C to T … (more)
The p.R106W pathogenic mutation (also known as c.316C>T and 390C>T), located in coding exon 2 of the MECP2 gene, results from a C to T substitution at nucleotide position 316. The arginine at codon 106 is replaced by tryptophan, an amino acid with dissimilar properties. This mutation was observed in two maternally related half-sisters with Rett syndrome; of note, their mother did not carry the p.R106W mutation indicating the presence of gonadal mosaicism (Amir RE et al. Nat. Genet., 1999 Oct;23:185-8). In another study, this mutation was identified in seven unrelated girls from the Australian Rett Syndrome Database, who had been diagnosed clinically or genetically with Rett syndrome (Knight O et al. Brain Dev., 2013 Nov;35:912-20) This mutation is located in the methyl-cytosine-binding domain (MBD) of the MECP2 protein and impairs its ability to bind and organize pericentric heterochromatin (Agarwal N et al. Hum. Mol. Genet., 2011 Nov;20:4187-95) and selectivity for methylated DNA (Ballestar E et al. Biochemistry, 2000 Jun;39:7100-6; Yusufzai TM et al. Nucleic Acids Res., 2000 Nov;28:4172-9). Two different alterations at the same position, p.R106G and p.R106Q, have been seen in three individuals from the French Cohort of Rett syndrome patients (Bienvenu T et al. Hum. Mol. Genet., 2000 May;9:1377-84). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jan 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
de novo
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV003804242.1
First in ClinVar: Feb 25, 2023 Last updated: Feb 25, 2023 |
|
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Pathogenic
(Dec 11, 2023)
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criteria provided, single submitter
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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Centre for Population Genomics, CPG
Accession: SCV004232325.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert … (more)
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: This variant is absent from gnomAD (PM2_Supporting).Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). This variant has been identified as a de novo occurrence with confirmed parental relationships in at least 2 individuals with Rett syndrome, or in at least 1 individual with confirmed parental relationships AND assumed the novo in at least 2 individuals with unconfirmed parental relationships (PS2_Very_Strong). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4).Well-established in vitro or in vivo functional studies supportive of a damaging effect on the protein function (PS3_supporting). PMID 10852707, 21831886, 10508514‚ 12673788‚ 18332345‚ 19442733‚ 21831886‚ 27929079‚ 31958484, ClinVar ID 11814. (less)
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Pathogenic
(Sep 01, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246094.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 7
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Pathogenic
(Mar 25, 2019)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157005.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The MECP2 c.316C>T; p.Arg106Trp variant (rs28934907) has been reported in patients with Rett syndrome (Amir 1999, Psoni 2010). MECP2 protein containing the variant has a … (more)
The MECP2 c.316C>T; p.Arg106Trp variant (rs28934907) has been reported in patients with Rett syndrome (Amir 1999, Psoni 2010). MECP2 protein containing the variant has a reduced binding affinity for methylated DNA (Ballestar 2000, Yusufzai 2000). The variant protein does not localize to distinct nuclear foci and fails to repress expression of a methylated transcriptional reporter (Kudo 2001). Hippocampal pyramidal neurons overexpressing the p.Arg106Trp variant protein have a lower density of mature dendritic spines after 48 hours of culture (Chapleau 2009). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 11814). It is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 106 is highly conserved and lies within the methyl-CpG binding domain. Computational algorithms (Align GV/GD, Mutation Taster, PolyPhen-2, SIFT) predict that this variant is deleterious. Based on available information, this variant is considered to be pathogenic. REFERENCES Amir RE et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. Ballestar E et al. Effects of Rett syndrome mutations of the methyl-CpG binding domain of the transcriptional repressor MeCP2 on selectivity for association with methylated DNA. Biochemistry. 2000 Jun 20;39(24):7100-6. Chapleau CA et al. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis. 2009 Aug;35(2):219-33. Kudo S et al. Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems. Brain Dev. 2001 Dec;23 Suppl 1:S165-73. Psoni S et al. Phenotypic and genotypic variability in four males with MECP2 gene sequence aberrations including a novel deletion. Pediatr Res. 2010 May;67(5):551-6. Yusufzai TM et al. Functional consequences of Rett syndrome mutations on human MeCP2. Nucleic Acids Res. 2000 Nov 1;28(21):4172-9. (less)
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Pathogenic
(Oct 28, 2019)
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criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001251404.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Pathogenic
(Jun 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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Severe neonatal-onset encephalopathy with microcephaly
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV001523354.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing in multiple individuals with … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing in multiple individuals with Rett syndrome [PMID: 16077729, 11058114, 10508514, 10852707, 20098342] (less)
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Pathogenic
(Jan 01, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
de novo
|
Provincial Medical Genetics Program of British Columbia, University of British Columbia
Accession: SCV002320828.1
First in ClinVar: Apr 08, 2022 Last updated: Apr 08, 2022 |
Sex: female
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Pathogenic
(Oct 26, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Heidelberg University
Accession: SCV002757813.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
Sex: female
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Pathogenic
(Jan 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321873.10
First in ClinVar: Oct 09, 2016 Last updated: Mar 04, 2023 |
Comment:
Reported as a common pathogenic variant in association with Rett syndrome (Amir et al., 1999; Vilchis et al., 2014; RettBASE); Published functional studies suggest it … (more)
Reported as a common pathogenic variant in association with Rett syndrome (Amir et al., 1999; Vilchis et al., 2014; RettBASE); Published functional studies suggest it significantly impairs the binding of methylated DNA (Ballestar et al., 2000); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24715477, 20098342, 23270700, 25789914, 19442733, 19217433, 25942534, 25900226, 20231667, 21831886, 11058114, 10852707, 25814391, 26017205, 26379794, 26418480, 26175308, 26278631, 25914188, 25779967, 25659951, 26108439, 26003587, 11738866, 12843318, 27929079, 16077729, 29631775, 30202406, 30564305, 29655203, 10508514, 31095231, 28920956, 32730690, 32369273, 31130284, 33258288, 32105570, 32472557) (less)
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Likely pathogenic
(Apr 24, 2020)
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criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Laboratoire de Génétique Moléculaire, CHU Bordeaux
Accession: SCV003836679.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Severe neonatal-onset encephalopathy with microcephaly Syndromic X-linked intellectual disability Lubs type Autism, susceptibility to, X-linked 3 X-linked intellectual disability-psychosis-macroorchidism syndrome Rett syndrome Rett syndrome
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920189.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
MECP2 NM_004992.3 exon 3 p.Arg106Trp (c.316C>T): This variant has been reported in the literature in several individuals with Rett syndrome (male and female), with multiple … (more)
MECP2 NM_004992.3 exon 3 p.Arg106Trp (c.316C>T): This variant has been reported in the literature in several individuals with Rett syndrome (male and female), with multiple cases reported to be de novo (Amir 1999 PMID:10508514, Glaze 2010 PMID:20231667, Psoni 2010 PMID:20098342, Knight 2013 PMID:23270700, Vilchis 2014 PMID:24715477, Pidcock 2016 PMID:26175308, Shioda 2018 PMID:29631775, RettBASE). Literature suggests that this variant accounts for up to 4.4% of pathogenic variants in MECP2 (Philippe 2006 PMID:16473305, Neul 2008 PMID:18337588, Vilchis 2014 PMID:24715477, RettBASE). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic or likely pathogenic (Variation ID:11814). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In vitro functional studies support that this variant impacts the protein through impaired binding affinity to methylated CpGs (Kudo 2001 PMID:11738866, Kudo 2003 PMID:12843318, Agarwal 2011 PMID:21831886). In addition, expression studies of this variant in cultured neurons from postportum brain samples showed significant reduction in dendritic spine dennsity compared to wildtype (Chapleau 2009 PMID:19442733). However, these studies may not accurately represent in vivo biological function. Additionally, this variant is located in the methyl binding domain, where the majority of pathogenic variants in MECP2 have been identified (Philippe 2006 PMID:16473305). In summary, this variant is classified as pathogenic based on the data above. (less)
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Pathogenic
(Apr 16, 2012)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220012.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in multiple individuals with Rett … (more)
It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in multiple individuals with Rett syndrome (PMIDs: 27929079 (2022), 32472557 (2020), 23270700 (2013), 20231667 (2010), 20098342 (2010), 10508514 (1999)). Experimental studies have indicated that the variant is damaging to MECP2 protein function (PMIDs: 27929079 (2016), 21831886 (2011), 19442733 (2009), 12843318 (2003), 11738866 (2001)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Jan 15, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Severe neonatal-onset encephalopathy with microcephaly
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000645663.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 106 of the MECP2 protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 106 of the MECP2 protein (p.Arg106Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Rett syndrome (PMID: 10508514, 18332345, 20098342, 23270700, 23421866). ClinVar contains an entry for this variant (Variation ID: 11814). 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: 12843318, 19442733, 21831886). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jun 12, 2013)
|
no assertion criteria provided
Method: curation
|
Rett syndrome
Affected status: unknown, yes
Allele origin:
unknown,
de novo
|
RettBASE
Accession: SCV000188054.2
First in ClinVar: Aug 15, 2014 Last updated: Apr 24, 2015 |
Observation 1:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 2:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 3:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 4:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Not known
Observation 5:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Not known
Observation 6:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 7:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 8:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 9:
Number of individuals with the variant: 1
Sex: female
Tissue: Not Known
Comment on evidence:
Not known
Observation 10:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 11:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 12:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 13:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 14:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Not known
Observation 15:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 16:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 17:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 18:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 19:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 20:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 21:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 22:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 23:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 24:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 25:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 26:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 27:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 28:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 29:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Classical
Observation 30:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 31:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 32:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 33:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 34:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 35:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Forme fruste
Observation 36:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 37:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 38:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 39:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 40:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 41:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 42:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 43:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 44:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 45:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 46:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 47:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 48:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 49:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 50:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 51:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 52:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 53:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - classical
Observation 54:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 55:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 56:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 57:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 58:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Atypical
Observation 59:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 60:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 61:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 62:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood or fibroblasts
Comment on evidence:
Rett syndrome - classical
Observation 63:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 64:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 65:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 66:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 67:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 68:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 69:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 70:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 71:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 72:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 73:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Preserved speech
Observation 74:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 75:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 76:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 77:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 78:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 79:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 80:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 81:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 82:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 83:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 84:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 85:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 86:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 87:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 88:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 89:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 90:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 91:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 92:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 93:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 94:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 95:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 96:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 97:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 98:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 99:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 100:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 101:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 102:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 103:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 104:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 105:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 106:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 107:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 108:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 109:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 110:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 111:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 112:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 113:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 114:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 115:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 116:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: brain
Comment on evidence:
Rett syndrome - Not certain
Observation 117:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 118:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 119:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 120:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 121:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 122:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 123:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Atypical
|
|
Pathogenic
(Oct 01, 1999)
|
no assertion criteria provided
Method: literature only
|
RETT SYNDROME
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000032820.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 03, 2018 |
Comment on evidence:
In 2 affected half sisters of a family with Rett syndrome (RTT; 312750), Amir et al. (1999) identified a 390C-T transition in the MECP2 gene, … (more)
In 2 affected half sisters of a family with Rett syndrome (RTT; 312750), Amir et al. (1999) identified a 390C-T transition in the MECP2 gene, resulting in an arg106-to-trp (R106W) substitution. (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929902.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951157.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Modeling RTT Syndrome by iPSC-Derived Neurons from Male and Female Patients with Heterogeneously Severe Hot-Spot MECP2 Variants. | Perego S | International journal of molecular sciences | 2022 | PMID: 36430969 |
Variation spectrum of MECP2 in Korean patients with Rett and Rett-like syndrome: a literature review and reevaluation of variants based on the ClinGen guideline. | Kim JA | Journal of human genetics | 2022 | PMID: 35606502 |
MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort. | Wen Y | Clinical genetics | 2020 | PMID: 32472557 |
Two novel mutations in the MECP2 gene in patients with Rett syndrome. | Khalili Alashti S | Gene | 2020 | PMID: 31958484 |
MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome. | Takeguchi R | Molecular genetics & genomic medicine | 2020 | PMID: 31816669 |
From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2. | Sheikh TI | Scientific reports | 2016 | PMID: 27929079 |
The high frequency of genetic diseases in hypotonic infants referred by neuropediatrics. | Vilchis Z | American journal of medical genetics. Part A | 2014 | PMID: 24715477 |
Using a large international sample to investigate epilepsy in Rett syndrome. | Bao X | Developmental medicine and child neurology | 2013 | PMID: 23421866 |
Pubertal trajectory in females with Rett syndrome: a population-based study. | Knight O | Brain & development | 2013 | PMID: 23270700 |
Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations. | Das DK | Gene | 2013 | PMID: 23262346 |
Genetic and epileptic features in Rett syndrome. | Kim HJ | Yonsei medical journal | 2012 | PMID: 22476991 |
MECP2 mutations and clinical correlations in Greek children with Rett syndrome and associated neurodevelopmental disorders. | Psoni S | Brain & development | 2012 | PMID: 21982064 |
Molecular screening of MECP2 gene in a cohort of Lebanese patients suspected with Rett syndrome: report on a mild case with a novel indel mutation. | Corbani S | Journal of intellectual disability research : JIDR | 2012 | PMID: 21954873 |
MeCP2 Rett mutations affect large scale chromatin organization. | Agarwal N | Human molecular genetics | 2011 | PMID: 21831886 |
Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations. | Hadzsiev K | Journal of human genetics | 2011 | PMID: 21160487 |
Epilepsy and the natural history of Rett syndrome. | Glaze DG | Neurology | 2010 | PMID: 20231667 |
Phenotypic and genotypic variability in four males with MECP2 gene sequence aberrations including a novel deletion. | Psoni S | Pediatric research | 2010 | PMID: 20098342 |
Genotype-phenotype correlation in Brazillian Rett syndrome patients. | Lima FT | Arquivos de neuro-psiquiatria | 2009 | PMID: 19722030 |
Spectrum of MECP2 mutations in New Zealand Rett syndrome patients. | Raizis AM | The New Zealand medical journal | 2009 | PMID: 19652677 |
Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. | Chapleau CA | Neurobiology of disease | 2009 | PMID: 19442733 |
Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. | Neul JL | Neurology | 2008 | PMID: 18337588 |
Investigating genotype-phenotype relationships in Rett syndrome using an international data set. | Bebbington A | Neurology | 2008 | PMID: 18332345 |
Rett syndrome: prevalence among Chinese and a comparison of MECP2 mutations of classic Rett syndrome with other neurodevelopmental disorders. | Wong VC | Journal of child neurology | 2007 | PMID: 18174559 |
Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms. | Zahorakova D | Journal of human genetics | 2007 | PMID: 17387578 |
MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome. | Li MR | Journal of human genetics | 2007 | PMID: 17089071 |
Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. | Philippe C | European journal of medical genetics | 2006 | PMID: 16473305 |
p.R270X MECP2 mutation and mortality in Rett syndrome. | Jian L | European journal of human genetics : EJHG | 2005 | PMID: 16077729 |
Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms. | Fukuda T | Brain & development | 2005 | PMID: 15737703 |
Mutation analysis of MECP2 and determination of the X-inactivation pattern in Hungarian Rett syndrome patients. | Kárteszi J | American journal of medical genetics. Part A | 2004 | PMID: 15389714 |
Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. | Schanen C | American journal of medical genetics. Part A | 2004 | PMID: 15057977 |
Mutations and polymorphisms in the human methyl CpG-binding protein MECP2. | Miltenberger-Miltenyi G | Human mutation | 2003 | PMID: 12872250 |
Heterogeneity in residual function of MeCP2 carrying missense mutations in the methyl CpG binding domain. | Kudo S | Journal of medical genetics | 2003 | PMID: 12843318 |
RettBASE: The IRSA MECP2 variation database-a new mutation database in evolution. | Christodoulou J | Human mutation | 2003 | PMID: 12673788 |
MECP2 mutations in Israel: implications for molecular analysis, genetic counseling, and prenatal diagnosis in Rett syndrome. | Yaron Y | Human mutation | 2002 | PMID: 12325033 |
Spectrum of MECP2 mutations in Rett syndrome. | Bienvenu T | Genetic testing | 2002 | PMID: 12180070 |
Influence of mutation type and location on phenotype in 123 patients with Rett syndrome. | Huppke P | Neuropediatrics | 2002 | PMID: 12075485 |
Mutation analysis in Rett syndrome. | Milunsky JM | Genetic testing | 2001 | PMID: 11960578 |
Rett syndrome in Spain: mutation analysis and clinical correlations. | Monrós E | Brain & development | 2001 | PMID: 11738885 |
Spectrum and distribution of MECP2 mutations in 64 Italian Rett syndrome girls: tentative genotype/phenotype correlation. | Giunti L | Brain & development | 2001 | PMID: 11738883 |
Functional analyses of MeCP2 mutations associated with Rett syndrome using transient expression systems. | Kudo S | Brain & development | 2001 | PMID: 11738866 |
Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech. | Yamashita Y | Brain & development | 2001 | PMID: 11738864 |
MECP2 mutation screening in Swedish classical Rett syndrome females. | Erlandson A | European child & adolescent psychiatry | 2001 | PMID: 11469283 |
MeCP2 mutations in children with and without the phenotype of Rett syndrome. | Hoffbuhr K | Neurology | 2001 | PMID: 11402105 |
MECP2 mutations in Danish patients with Rett syndrome: high frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern. | Nielsen JB | European journal of human genetics : EJHG | 2001 | PMID: 11313756 |
MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. | Trappe R | American journal of human genetics | 2001 | PMID: 11309679 |
Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females. | Vacca M | Journal of molecular medicine (Berlin, Germany) | 2001 | PMID: 11269512 |
MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features. | Auranen M | Neurology | 2001 | PMID: 11245712 |
Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions. | Laccone F | Human mutation | 2001 | PMID: 11241840 |
MECP2 mutation in non-fatal, non-progressive encephalopathy in a male. | Imessaoudene B | Journal of medical genetics | 2001 | PMID: 11238684 |
A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients. | Bourdon V | Human genetics | 2001 | PMID: 11214906 |
Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. | Lam CW | Journal of medical genetics | 2000 | PMID: 11106359 |
Functional consequences of Rett syndrome mutations on human MeCP2. | Yusufzai TM | Nucleic acids research | 2000 | PMID: 11058114 |
Diagnostic testing for Rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene: identification of several novel mutations and polymorphisms. | Buyse IM | American journal of human genetics | 2000 | PMID: 11055898 |
Mutations in the MECP2 gene in a cohort of girls with Rett syndrome. | Hampson K | Journal of medical genetics | 2000 | PMID: 10991689 |
Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in patients with Rett syndrome. | Obata K | Journal of medical genetics | 2000 | PMID: 10991688 |
Effects of Rett syndrome mutations of the methyl-CpG binding domain of the transcriptional repressor MeCP2 on selectivity for association with methylated DNA. | Ballestar E | Biochemistry | 2000 | PMID: 10852707 |
MECP2 mutations account for most cases of typical forms of Rett syndrome. | Bienvenu T | Human molecular genetics | 2000 | PMID: 10814719 |
Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients. | Huppke P | Human molecular genetics | 2000 | PMID: 10814718 |
Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. | Cheadle JP | Human molecular genetics | 2000 | PMID: 10767337 |
Mutation screening in Rett syndrome patients. | Xiang F | Journal of medical genetics | 2000 | PMID: 10745042 |
Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. | Wan M | American journal of human genetics | 1999 | PMID: 10577905 |
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. | Amir RE | Nature genetics | 1999 | PMID: 10508514 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MECP2 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d4ad766a-373e-4a8a-a940-5343d0357481 | - | - | - | - |
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Text-mined citations for rs28934907 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.