ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)
Variation ID: 11824 Accession: VCV000011824.70
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154030912 (GRCh38) [ NCBI UCSC ] X: 153296363 (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 Jul 15, 2024 Mar 26, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.952C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Arg318Cys missense NM_004992.4:c.916C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Arg306Cys missense NM_001316337.2:c.637C>T NP_001303266.1:p.Arg213Cys missense NM_001369391.2:c.637C>T NP_001356320.1:p.Arg213Cys missense NM_001369392.2:c.637C>T NP_001356321.1:p.Arg213Cys missense NM_001369393.2:c.637C>T NP_001356322.1:p.Arg213Cys missense NM_001369394.2:c.637C>T NP_001356323.1:p.Arg213Cys missense NM_001386137.1:c.247C>T NP_001373066.1:p.Arg83Cys missense NM_001386138.1:c.247C>T NP_001373067.1:p.Arg83Cys missense NM_001386139.1:c.247C>T NP_001373068.1:p.Arg83Cys missense NM_004992.3(MECP2):c.916C>T NC_000023.11:g.154030912G>A NC_000023.10:g.153296363G>A NG_007107.3:g.111192C>T LRG_764:g.111192C>T LRG_764t1:c.952C>T LRG_764p1:p.Arg318Cys LRG_764t2:c.916C>T LRG_764p2:p.Arg306Cys P51608:p.Arg306Cys AJ132917.1:c.916C>T - Protein change
- R306C, R318C, R213C, R83C
- Other names
- p.R306C:CGC>TGC
- p.Arg318Cys
- NM_001110792.2(MECP2):c.952C>T
- Canonical SPDI
- NC_000023.11:154030911:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Unknown function
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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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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
Help
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 |
1848 | 2175 |
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 (24) |
reviewed by expert panel
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Mar 26, 2021 | RCV000012597.63 | |
Pathogenic (14) |
criteria provided, multiple submitters, no conflicts
|
Jul 18, 2023 | RCV000081218.58 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 25, 2014 | RCV000224156.9 | |
Pathogenic (1) |
no assertion criteria provided
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Feb 20, 2006 | RCV000202468.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2024 | RCV000466020.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 1, 2021 | RCV001841244.9 | |
See cases
|
Pathogenic (1) |
criteria provided, single submitter
|
Jan 23, 2019 | RCV002287332.8 |
Pathogenic (1) |
criteria provided, single submitter
|
- | RCV002273927.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Dec 6, 2018 | RCV002444428.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV003224093.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 12, 2024 | RCV004532325.1 | |
click to load more click to collapse |
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
(Mar 26, 2021)
|
reviewed by expert panel
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001711972.1 First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021 |
Comment:
The p.Arg306Cys variant in MECP2 has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 individuals with … (more)
The p.Arg306Cys variant in MECP2 has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 individuals with Rett Syndrome (PMID 10577905, 11309679, 19189931; internal database, GeneDx) (PS2_very strong). This variant has been observed in at least 4 other individuals with Rett syndrome (PMID 24511209, 23238081, RettBase) (PS4). The p.Arg306Cys variant occurs in the well-characterized transcriptional repression domain (TRD) functional domain of MECP2 (PMID 21326358, 23770565) (PM1). This variant is absent in gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, p.Arg306Cys variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2_very strong, PS4, PM1, PM2_supporting, PP3). (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Rett's disorder
Affected status: yes
Allele origin:
unknown
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Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics
Accession: SCV000223842.1
First in ClinVar: Jun 10, 2015 Last updated: Jun 10, 2015 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000248005.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
|
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Pathogenic
(May 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes
Accession: SCV000920485.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
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Pathogenic
(Jun 29, 2016)
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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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Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine
Accession: SCV000994545.1
First in ClinVar: Sep 27, 2019 Last updated: Sep 27, 2019 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
unknown
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Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn
Accession: SCV000999382.1
First in ClinVar: Dec 01, 2019 Last updated: Dec 01, 2019 |
Number of individuals with the variant: 1
Clinical Features:
Inappropriate laughter (present) , Delayed speech and language development (present) , Cognitive impairment (present) , Developmental regression (present) , Autistic disorder of childhood onset (present) … (more)
Inappropriate laughter (present) , Delayed speech and language development (present) , Cognitive impairment (present) , Developmental regression (present) , Autistic disorder of childhood onset (present) , Atonic seizures (present) , Autistic behavior (present) , Seizures (present) , Stereotypical hand wringing (present) (less)
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Pathogenic
(Aug 09, 2019)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001524905.1
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].
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Pathogenic
(Nov 01, 2021)
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criteria provided, single submitter
Method: research
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Autism, susceptibility to, X-linked 3
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102399.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
Comment:
A heterozygous missense variation in exon 3 of the MECP2 gene that results in the amino acid substitution of Cysteine for Arginine at codon 318 … (more)
A heterozygous missense variation in exon 3 of the MECP2 gene that results in the amino acid substitution of Cysteine for Arginine at codon 318 was detected. The observed variant c.952C>T (p.Arg318Cys) has not been reported in the 1000 genomes and gnomAD databases. The in-silico predictions of the variant are damaging by PolyPhen-2 (HumDiv), SIFT, LRT and MutationTaster2. The reference codon is conserved across species. This variant has previously been reported in patients affected with Rett syndrome. Segregation analysis showed the variant to be of de novo origin. In summary, the variant meets our criteria to be classified as a pathogenic variant. (less)
Clinical Features:
Mild global developmental delay (present) , Absent speech (present) , Preauricular pit (present) , Few cafe-au-lait spots (present) , Bruxism (present) , Hyperactivity (present) , … (more)
Mild global developmental delay (present) , Absent speech (present) , Preauricular pit (present) , Few cafe-au-lait spots (present) , Bruxism (present) , Hyperactivity (present) , Impaired social interactions (present) (less)
Age: 0-9 years
Sex: female
Ethnicity/Population group: Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Pathogenic
(Jan 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002578069.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
ACMG categories: PS2,PM2,PM5,PP3,PP4,PP5
Number of individuals with the variant: 1
Clinical Features:
Absent speech (present) , Gait ataxia (present) , Stereotypical hand wringing (present) , Broad face (present)
Age: 0-9 years
Sex: female
Tissue: blood
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV003841464.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID: 34837432). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.84; 3Cnet: 0.82). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000011824). The variant has been previously reported as de novo in at least two similarly affected unrelated individuals (PMID: 10577905, 11309679, 19189931). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 2323808, 24511209). Different missense changes at the same codon (p.Arg318His, p.Arg318Leu, p.Arg318Pro) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000143746, VCV000143747, VCV000521860). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Global developmental delay (present) , Microcephaly (present)
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Pathogenic
(Mar 30, 2021)
|
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: SCV003920185.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
MECP2 NM_004992.3 exon4 p.Arg306Cys (c.916C>T): This variant is one of the most common pathogenic variants in MECP2 and has been reported in the literature in … (more)
MECP2 NM_004992.3 exon4 p.Arg306Cys (c.916C>T): This variant is one of the most common pathogenic variants in MECP2 and has been reported in the literature in several individuals with Rett syndrome incliuding at least two de novo occurrences (Wan 1999 PMID: 10577905; Yamashita 2001 PMID: 11738864, Jian 2005 PMID: 16077729; Voutoufianakis 2007 PMID: 17276711; Fendri-Kriaa 2009; PMID: 19309283; Delepine 2013 PMID: 23238081; Cortelazzo 2014 PMID: 24511209; Livide 2015 PMID: 24970834; Pidcock 2016 PMID: 26175308; Zhang 2017 PMID: 28394482; Lindy 2018 29655203; Long 2019 31139143; Scocchia 2019 30792901). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID: 11824). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Additionally, both in vitro and in vivo functional studies have shown a deleterious effect for this variant (Delepine 2013 PMID: 23238081; Ebert 2013 PMID: 23770587; Lyst 2013 PMID: 23770656; Heckman 2014 PMID: 24970834; Livide 2015 PMID: 24970834; Brown 2016 PMID: 26647311). However, these studies may not accurately represent in vivo human biological function. In summary, this variant is classified as pathogenic based on the data above. (less)
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Pathogenic
(Aug 14, 2023)
|
criteria provided, single submitter
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
|
Centre for Population Genomics, CPG
Accession: SCV004098728.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
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 Panel … (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 2.0, this variant is classified as pathogenic. At least the following criteria are met: 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). Occurs in the well-characterized Transcriptional repression domain (TRD) of MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact (REVEL score ≥ 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting). (less)
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Pathogenic
(Jul 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002017252.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Jan 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Severe neonatal-onset encephalopathy with microcephaly
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000544613.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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. (less)
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Pathogenic
(Jan 12, 2024)
|
criteria provided, single submitter
Method: clinical testing
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MECP2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004745453.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The MECP2 c.916C>T variant is predicted to result in the amino acid substitution p.Arg306Cys. This variant has been reported to be causative for Rett Syndrome … (more)
The MECP2 c.916C>T variant is predicted to result in the amino acid substitution p.Arg306Cys. This variant has been reported to be causative for Rett Syndrome (Wan et al. 1999. PubMed ID: 10577905; Aldosary et al. 2020. PubMed ID: 32105570; OMIM: #312750). The pathogenicity of this recurrent variant is supported by functional studies, as well as its presence in numerous affected individuals (Brown et al. 2016. PubMed ID: 26647311). Some studies indicate a favorable outcome with increased mobility and delayed regression resulting from this change, in comparison to other pathogenic MECP2 variants (Schanen et al. 2004. PubMed ID: 15057977; Pidcock et al. 2016. PubMed ID: 26175308). While more than 99% of pathogenic MECP2 variants occur de novo in the affected patient, at least one case of maternal transmission is reported for the p.Arg306Cys missense change (Wan et al. 1999. PubMed ID: 10577905). Variably skewed X-chromosome inactivation is predicted to underlie the range of phenotypic severity observed in individuals with this change (Wan et al. 1999. PubMed ID: 10577905). Of note, other missense variants affecting the same amino acid (p.Arg306His, p.Arg306Pro, p.Arg306Leu) have also been reported to be pathogenic for Rett syndrome (HGMD database; Cheadle et al. 2000. PubMed ID: 10767337). Taken together, we interpret this variant as pathogenic. (less)
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Pathogenic
(Aug 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV004801532.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
The MECP2 c.916C>T p.(Arg306Cys) missense variant has been reported in at least six studies in which it was found in a total of 39 individuals … (more)
The MECP2 c.916C>T p.(Arg306Cys) missense variant has been reported in at least six studies in which it was found in a total of 39 individuals with Rett syndrome (Wan et al. 1999; Bourdon et al. 2001; Schanen et al. 2004; Li et al. 2007; Cortelazzo et al. 2014; Pidcock et al. 2016). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies in patient fibroblasts and cultured cortical neurons, demonstrated that the p.(Arg306Cys) variant protein resulted in almost total depolymerization of microtubules under the effect of cold-induced stress and also rendered the variant protein incapable of interacting with the nuclear receptor co-repressor complex as compared with wildtype protein (Delépine et al. 2013; Ebert et al. 2013). In addition, transgenic mice expressing the p.(Arg306Cys) variant protein recapitulated many of the phenotypes seen in affected individuals (Heckman et al. 2014; Brown et al. 2015). Based on the collective evidence, the c.916C>T p.(Arg306Cys) variant is classified as pathogenic for Rett syndrome. (less)
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Pathogenic
(Jul 25, 2014)
|
criteria provided, single submitter
Method: clinical testing
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Intellectual disability
Affected status: yes
Allele origin:
de novo
|
Diagnostic Laboratory, Strasbourg University Hospital
Accession: SCV000281744.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Number of individuals with the variant: 1
Sex: female
|
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Pathogenic
(Aug 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
de novo
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610040.1
First in ClinVar: Jan 07, 2017 Last updated: Jan 07, 2017 |
|
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Pathogenic
(May 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698547.1
First in ClinVar: Mar 03, 2018 Last updated: Mar 03, 2018 |
Comment:
Variant summary: The MECP2 c.916C>T (p.Arg306Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging … (more)
Variant summary: The MECP2 c.916C>T (p.Arg306Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional studies showed that this variant decreased microtubule (MT) stability and down-regulated GRID1, a gene in the neurotransmitter pathway which is known to be down-regulated in the absence of functional MECP2 (Delepine_FEBSL_2013, Livide_EJHG_2014). In addition, a study using the Mecp2R306C mouse knock-out model recapitulated RTT-like features, such as compromised mobility and motor coordination and reduction in brain weight (Lyst_Natneurosci_2013). This variant is absent in 87936 control chromosomes including broad and large populations from ExAC. This variant was reported in numerous patients with RTT syndrome (Buyse_AJHG_2000, Obata_JMG_2000, Xiang_JMG_2000), including instances of de novo occurrence and it is considered the second most common RTT-causing missense mutation. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781714.1
First in ClinVar: Jul 07, 2018 Last updated: Jul 07, 2018 |
|
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Pathogenic
(Jul 09, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
de novo
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV000928372.1
First in ClinVar: Jul 31, 2019 Last updated: Jul 31, 2019 |
Comment:
PS4, PM1, PM2, PM5, PP3, PP4, PP5
|
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Pathogenic
(Feb 04, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000230267.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 7
Sex: mixed
|
|
Pathogenic
(Jun 27, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001426148.1
First in ClinVar: Aug 03, 2020 Last updated: Aug 03, 2020 |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
de novo
|
Centogene AG - the Rare Disease Company
Accession: SCV001426580.1
First in ClinVar: Aug 10, 2020 Last updated: Aug 10, 2020 |
|
|
Pathogenic
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440007.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
|
|
Pathogenic
(Jul 26, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001445896.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
This variant is also referred to in the literature as c.916C>T (p.Arg306Cys) due to use of a different reference transcript (NM_004992.3). This variant is a … (more)
This variant is also referred to in the literature as c.916C>T (p.Arg306Cys) due to use of a different reference transcript (NM_004992.3). This variant is a recurrent alteration that has been reported in multiple individuals with Rett syndrome (PMID: 10577905, 26175308, 29655203, 30792901, 11738864, 19309283, 28394482). RettBASE, a MECP2 variation database, reports the p.Arg318Cys change accounts for approximately 5% of Rett syndrome diagnoses (http://mecp2.chw.edu.au/) (PMID: 28544139). This variant has also been reported as Pathogenic by multiple clinical diagnostic laboratories in the ClinVar database (Variation ID: 11824). Functional studies have shown this missense variant disrupts the ability of the MeCP2 protein to associate with co-repressors (PMID: 23770587, 23770565, 24970834), impairs DNA-binding in vivo and in vitro (PMID: 26647311, 11058114), and results in decreased microtubule stability (PMID: 23238081). The c.952C>T (p.Arg318Cys) variant is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. It affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.952C>T (p.Arg318Cys) variant is classified as Pathogenic. (less)
|
|
Pathogenic
(Apr 16, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000190987.9
First in ClinVar: Nov 01, 2014 Last updated: Apr 17, 2019 |
Comment:
Published functional studies demonstrate that the R306C variant results in a damaging effect (Heckman et al., 2014; Kruusvee et al., 2017); Not observed in large … (more)
Published functional studies demonstrate that the R306C variant results in a damaging effect (Heckman et al., 2014; Kruusvee et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23770565, 11058114, 27428650, 26647311, 28212680, 32393352, 24511209, 10577905, 23770587, 23238081, 24970834, 24916645, 28348241, 19309283, 16077729, 26175308, 17276711, 11738864, 28394482, 29655203, 30792901, 31139143, 31095231, 25762136, 30577886, 12030010, 31130284, 33278787) (less)
|
|
Pathogenic
(Dec 24, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884099.3
First in ClinVar: Feb 17, 2019 Last updated: Jan 08, 2022 |
Comment:
The MECP2 c.916C>T; p.Arg306Cys variant (rs28935468) is a recurrent alteration in individuals diagnosed with Rett syndrome, and often found as a de novo change (Cheadle … (more)
The MECP2 c.916C>T; p.Arg306Cys variant (rs28935468) is a recurrent alteration in individuals diagnosed with Rett syndrome, and often found as a de novo change (Cheadle 2000, Wan 1999, RettBase). Transgenic mice expressing the variant protein show developmental and behavioral phenotypes reminiscent of the clinical symptoms found in human patients (Brown 2016, Heckman 2014). Functional characterization of the MECP2 variant protein indicates disruption in its association with co-repressors, such as HDAC3 and the NCoR complex (Ebert 2013, Heckman 2014, Lyst 2013), and reduction in in-vivo DNA occupancy (Heckman 2014). This results in a failure of the MECP2 protein in mediating transcriptional repression at its targets (Ebert 2013, Lyst 2013). Another missense variant at this residue, p.Arg306His, has also been implicated in Rett syndrome (Cheadle 2000, RettBase). The p.Arg306Cys variant is listed as pathogenic in ClinVar (Variation ID: 11824), and is not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). Based on the above information, the p.Arg306Cys variant is classified as pathogenic. References: RettBase: http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic Brown K et al. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome. Hum Mol Genet. 2016; 25(3):558-70. Cheadle J et al. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet. 2000; 9(7):1119-29. Ebert D et al. Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR. Nature. 2013; 499(7458):341-5. Heckman L et al. Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife. 2014 Jun 26; 3. Lyst M et al. Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor. Nat Neurosci. 2013; 16(7):898-902. Wan M et al. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet. 1999; 65(6):1520-9. (less)
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
(X-linked inheritance)
Affected status: yes
Allele origin:
de novo
|
Suma Genomics
Accession: SCV002097337.1
First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022 |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental delay
Affected status: yes
Allele origin:
de novo
|
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV002558995.1
First in ClinVar: Aug 15, 2022 Last updated: Aug 15, 2022 |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820191.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
The missense variant p.R306C in MECP2 (NM_004992.4) has been previously reported in at least 4 individuals affected with Rett syndrome (Cortelazzo et al, 2014). Experimental … (more)
The missense variant p.R306C in MECP2 (NM_004992.4) has been previously reported in at least 4 individuals affected with Rett syndrome (Cortelazzo et al, 2014). Experimental studies have shown that this missense change abolishes the interaction between MECP2 and its co-repressor and impairs DNA-binding both in vitro and in vivo (Lyst et al, 2013; Heckman et al. 2014). The p.R306C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a large physicochemical difference between arginine and cysteine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The p.R306C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 306 of MECP2 is conserved in all mammalian species. The nucleotide c.916 in MECP2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic (less)
Clinical Features:
Delayed speech and language development (present) , Attention deficit hyperactivity disorder (present) , Atypical behavior (present) , Involuntary movements (present)
|
|
Pathogenic
(Dec 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
(X-linked inheritance)
Affected status: yes
Allele origin:
unknown
|
Molecular Diagnostics Lab, Nemours Children's Health, Delaware
Accession: SCV003935869.1
First in ClinVar: Jul 01, 2023 Last updated: Jul 01, 2023 |
Clinical Features:
Developmental regression (present) , Autistic behavior (present)
Age: 0-9 years
Sex: female
Tissue: blood
|
|
Pathogenic
(May 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002774385.2
First in ClinVar: Dec 31, 2022 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in multiple individuals affected with Rett syndrome (PMIDs: 10767337 (2000), 10814719 (2000), 23238081 (2013), and 24511209 … (more)
In the published literature, this variant has been reported in multiple individuals affected with Rett syndrome (PMIDs: 10767337 (2000), 10814719 (2000), 23238081 (2013), and 24511209 (2014)), and has been reported in multiple symptomatic individuals as a de novo occurrence (PMIDs: 10577905 (1999), 11309679 (2001), 19189931 (2009), and 32393352 (2020)). In addition, functional studies report this variant is damaging to MECP2 protein function (PMIDs: 23770565 (2013), 23770587 (2013), 24970834 (2014), and 26647311 (2016)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(May 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV004229773.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
This variant has been identified in multiple unrelated individuals with Rett syndrome and occurs de novo in multiple individuals. This variant has not been reported … (more)
This variant has been identified in multiple unrelated individuals with Rett syndrome and occurs de novo in multiple individuals. This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) In some published literature, this variant is referred to as c.990C>T and c.991C>T. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 23770565, 24970834, 23770587, 26647311) The variant is located in a region that is considered important for protein function and/or structure. (less)
|
|
Pathogenic
(Dec 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002683250.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R306C pathogenic mutation (also known as c.916C>T), located in coding exon 3 of the MECP2 gene, results from a C to T substitution at … (more)
The p.R306C pathogenic mutation (also known as c.916C>T), located in coding exon 3 of the MECP2 gene, results from a C to T substitution at nucleotide position 916. The arginine at codon 306 is replaced by cysteine, an amino acid with highly dissimilar properties. This mutation has been observed in multiple individuals with Rett syndrome, both inherited and de novo occurrences (Wan M et al. Am. J. Hum. Genet., 1999 Dec;65:1520-9; Buyse IM et al. Am. J. Hum. Genet., 2000 Dec;67:1428-36; Yamashita Y et al. Brain Dev., 2001 Dec;23 Suppl 1:S157-60; Heilstedt HA et al. Am. J. Med. Genet., 2002 Aug;111:238-42; Schanen C et al. Am. J. Med. Genet. A, 2004 Apr;126A:129-40; Zhang Q et al. Am. J. Med. Genet. B Neuropsychiatr. Genet., 2017 Jun;174:451-457). Functional studies demonstrated that this alteration had decreased microtubule stability, abolished the interaction of MeCP2 with the NCoR/SMRT co-repressor, and down regulated GRID1 expression (Delépine C et al. FEBS Lett., 2013 Jan;587:245-53; Lyst MJ et al. Nat. Neurosci., 2013 Jul;16:898-902; Livide G et al. Eur. J. Hum. Genet., 2015 Feb;23:195-201). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(Jul 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002063366.17
First in ClinVar: Jan 22, 2022 Last updated: Jul 15, 2024 |
Comment:
MECP2: PS2, PS4, PM2, PP3
Number of individuals with the variant: 2
|
|
Pathogenic
(Apr 15, 2004)
|
no assertion criteria provided
Method: literature only
|
RETT SYNDROME
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000032832.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 03, 2018 |
Comment on evidence:
In 2 unrelated patients with Rett syndrome (RTT; 312750), Bourdon et al. (2001) found a 916C-T transition in exon 3 of the MECP2 gene resulting … (more)
In 2 unrelated patients with Rett syndrome (RTT; 312750), Bourdon et al. (2001) found a 916C-T transition in exon 3 of the MECP2 gene resulting in an arg306-to-cys (R306C) amino acid change. The R306C mutation was also found in heterozygous state by Heilstedt et al. (2002) in a girl with atypical Rett syndrome manifested by developmental delay and hypotonia without evidence of an initial period of normal development. The mother did not carry the mutation. In a study of patients with mutations in the MECP2 gene, Schanen et al. (2004) found that the group of patients with the R306C mutation had a better prognosis, including better overall phenotype severity scores, later regression, and better speech with less motor impairment, than other mutation groups. (less)
|
|
Pathogenic
(Apr 03, 2015)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Additional submitter:
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000804261.1
First in ClinVar: Sep 01, 2018 Last updated: Sep 01, 2018 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808047.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 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: SCV001955633.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978724.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
Pathogenic
(Nov 02, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004101072.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
|
|
Pathogenic
(Feb 26, 2014)
|
no assertion criteria provided
Method: curation
|
Rett syndrome
Affected status: yes, unknown
Allele origin:
unknown,
de novo,
germline
|
RettBASE
Accession: SCV000188298.2
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 Rett synd.
Observation 2:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Not known
Observation 3:
Number of individuals with the variant: 1
Family history: No
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
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 10:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 11:
Number of individuals with the variant: 1
Family history: No
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
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
Comment on evidence:
Not known
Observation 18:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 19:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 20:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 21:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 22:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 23:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 24:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 25:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 26:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
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
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 30:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 31:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 32:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 33:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 34:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
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 - Classical
Observation 36:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Classical
Observation 37:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Classical
Observation 38:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Classical
Observation 39:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 40:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 41:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 42:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 43:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 44:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 45:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 46:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 47:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 48:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 49:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 50:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 51:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Not certain
Observation 52:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 53:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
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: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 56:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 57:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 58:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 59:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 60:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - preserved speech
Observation 61:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 62:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 63:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 64:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 65:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 66:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 67:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 68:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Atypical
Observation 69:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 70:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 71:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 72:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood or fibroblasts
Comment on evidence:
Rett syndrome - classical
Observation 73:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - classical
Observation 74:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - classical
Observation 75:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - classical
Observation 76:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - classical
Observation 77:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 78:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
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
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 82:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 83:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 84:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 85:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Classical
Observation 86:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 87:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphocytes
Comment on evidence:
Rett syndrome - Atypical
Observation 88:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 89:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 90:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 91:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 92:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 93:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 94:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 95:
Number of individuals with the variant: 1
Sex: female
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
Family history: No
Sex: female
Tissue: blood or fibroblasts
Comment on evidence:
Rett syndrome - classical
Observation 99:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: NK
Comment on evidence:
Rett syndrome - classical
Observation 100:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 101:
Number of individuals with the variant: 1
Family history: No
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 102:
Number of individuals with the variant: 1
Family history: No
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 103:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Preserved speech
Observation 104:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - classical
Observation 105:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: NK
Comment on evidence:
Rett syndrome - classical
Observation 106:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 107:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 108:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 109:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - classical
Observation 110:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - classical
Observation 111:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 112:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 113:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 114:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 115:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 116:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 117:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 118:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 119:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
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
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 - classical
Observation 124:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - classical
Observation 125:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 126:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 127:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 128:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 129:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 130:
Number of individuals with the variant: 1
Comment on evidence:
Rett syndrome - Not certain
Observation 131:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 132:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Preserved speech
Observation 133:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Preserved speech
Observation 134:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 135:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 136:
Number of individuals with the variant: 1
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - not certain
Observation 137:
Number of individuals with the variant: 1
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - not certain
Observation 138:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 139:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 140:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 141:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 142:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Not certain
Observation 143:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Not certain
Observation 144:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Not certain
Observation 145:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 146:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 147:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 148:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 149:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 150:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 151:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 152:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 153:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 154:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: not known
Comment on evidence:
Rett syndrome - forme fruste
Observation 155:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 156:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 157:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 158:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 159:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 160:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 161:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 162:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 163:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 164:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 165:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 166:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 167:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 168:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 169:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - atypical
Observation 170:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 171:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - atypical
Observation 172:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - atypical
Observation 173:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 174:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 175:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 176:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 177:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 178:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 179:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 180:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 181:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Atypical
Observation 182:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Atypical
Observation 183:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Atypical
Observation 184:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 185:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 186:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood or skin
Comment on evidence:
Rett syndrome - Classical
Observation 187:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 188:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 189:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 190:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 191:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
Rett syndrome - Not certain
Observation 192:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: lymphocytes for XCI
Comment on evidence:
Rett syndrome - forme fruste
Observation 193:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 194:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 195:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 196:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 197:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 198:
Number of individuals with the variant: 1
Family history: No
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 199:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 200:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 201:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 202:
Number of individuals with the variant: 1
Sex: female
Tissue: lymphoblastoid cell lines
Comment on evidence:
Rett syndrome - not certain
Observation 203:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
|
|
Pathogenic
(Feb 20, 2006)
|
no assertion criteria provided
Method: clinical testing
|
Angelman syndrome
Affected status: yes
Allele origin:
germline
|
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000257516.1
First in ClinVar: Dec 21, 2015 Last updated: Dec 21, 2015 |
Number of individuals with the variant: 1
Clinical Features:
Seizures (present) , Status epileptus (present)
|
|
Pathogenic
(Jun 26, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Rett syndrome
Affected status: yes
Allele origin:
germline
|
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000257515.1
First in ClinVar: Dec 17, 2015 Last updated: Dec 17, 2015 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Developmental delay (present) , Seizures (present)
|
|
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: SCV001932221.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Rett syndrome
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000998927.2
First in ClinVar: Nov 17, 2019 Last updated: Oct 01, 2022 |
|
|
click to load more click to collapse |
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
Unknown function
|
|
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102399.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods. | McKnight D | Human mutation | 2022 | PMID: 34837432 |
Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort. | Bertoli-Avella AM | European journal of human genetics : EJHG | 2021 | PMID: 32860008 |
Three intellectual disability-associated de novo mutations in MECP2 identified by trio-WES analysis. | Gu Y | BMC medical genetics | 2020 | PMID: 32393352 |
Familial cases and male cases with MECP2 mutations. | Zhang Q | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | 2017 | PMID: 28394482 |
The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome. | Brown K | Human molecular genetics | 2016 | PMID: 26647311 |
GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. | Livide G | European journal of human genetics : EJHG | 2015 | PMID: 24916645 |
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. | Redin C | Journal of medical genetics | 2014 | PMID: 25167861 |
Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. | Heckman LD | eLife | 2014 | PMID: 24970834 |
Subclinical inflammatory status in Rett syndrome. | Cortelazzo A | Mediators of inflammation | 2014 | PMID: 24511209 |
Brief report: MECP2 mutations in people without Rett syndrome. | Suter B | Journal of autism and developmental disorders | 2014 | PMID: 23921973 |
Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR. | Ebert DH | Nature | 2013 | PMID: 23770587 |
Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor. | Lyst MJ | Nature neuroscience | 2013 | PMID: 23770565 |
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 |
MeCP2 deficiency is associated with impaired microtubule stability. | Delépine C | FEBS letters | 2013 | PMID: 23238081 |
Spontaneous recurrent mutations and a complex rearrangement in the MECP2 gene in the light of current models of mutagenesis. | Todorov T | Mutation research | 2012 | PMID: 22525432 |
Genetic and epileptic features in Rett syndrome. | Kim HJ | Yonsei medical journal | 2012 | PMID: 22476991 |
Molecular diagnostic dilemmas in Rett syndrome. | Zvereff V | Brain & development | 2012 | PMID: 22277191 |
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 |
Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. | Cheung AY | Human molecular genetics | 2011 | PMID: 21372149 |
Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations. | Hadzsiev K | Journal of human genetics | 2011 | PMID: 21160487 |
MeCP2 deficiency downregulates specific nuclear proteins that could be partially recovered by valproic acid in vitro. | Vecsler M | Epigenetics | 2010 | PMID: 20093853 |
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 |
A novel MECP2 gene mutation in a Tunisian patient with Rett syndrome. | Fendri-Kriaa N | Genetic testing and molecular biomarkers | 2009 | PMID: 19309283 |
Methyl-CpG-binding protein 2 (MECP2) gene mutations in an Italian sample of patients with pervasive developmental disorder and mental retardation. | Parmeggiani A | Journal of child neurology | 2009 | PMID: 19189931 |
Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. | Neul JL | Neurology | 2008 | PMID: 18337588 |
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 |
MECP2 mutations in Serbian Rett syndrome patients. | Djarmati A | Acta neurologica Scandinavica | 2007 | PMID: 17986102 |
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 |
Coinheritance of mutated SMN1 and MECP2 genes in a child with phenotypic features of spinal muscular atrophy (SMA) type II and Rett syndrome. | Voutoufianakis S | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2007 | PMID: 17276711 |
MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome. | Li MR | Journal of human genetics | 2007 | PMID: 17089071 |
Very mild cases of Rett syndrome with skewed X inactivation. | Huppke P | Journal of medical genetics | 2006 | PMID: 16690727 |
Diagnostic mutational analysis of MECP2 in Korean patients with Rett syndrome. | Kim IJ | Experimental & molecular medicine | 2006 | PMID: 16672765 |
Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. | Philippe C | European journal of medical genetics | 2006 | PMID: 16473305 |
Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. | Archer HL | Journal of medical genetics | 2006 | PMID: 16183801 |
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 |
Influence of MECP2 gene mutation and X-chromosome inactivation on the Rett syndrome phenotype. | Chae JH | Journal of child neurology | 2004 | PMID: 15526954 |
Screening of MECP2 coding sequence in patients with phenotypes of decreasing likelihood for Rett syndrome: a cohort of 171 cases. | Kammoun F | Journal of medical genetics | 2004 | PMID: 15173251 |
Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. | Schanen C | American journal of medical genetics. Part A | 2004 | PMID: 15057977 |
InterRett and RettBASE: International Rett Syndrome Association databases for Rett syndrome. | Fyfe S | Journal of child neurology | 2003 | PMID: 14649554 |
Rett syndrome in adolescent and adult females: clinical and molecular genetic findings. | Smeets E | American journal of medical genetics. Part A | 2003 | PMID: 12966523 |
Mutations and polymorphisms in the human methyl CpG-binding protein MECP2. | Miltenberger-Miltenyi G | Human mutation | 2003 | PMID: 12872250 |
Mutation analysis of the MECP2 gene in patients with Rett syndrome. | Conforti FL | American journal of medical genetics. Part A | 2003 | PMID: 12567420 |
Gene expression patterns vary in clonal cell cultures from Rett syndrome females with eight different MECP2 mutations. | Traynor J | BMC medical genetics | 2002 | PMID: 12418965 |
Infantile hypotonia as a presentation of Rett syndrome. | Heilstedt HA | American journal of medical genetics | 2002 | PMID: 12210319 |
Spectrum of MECP2 mutations in Rett syndrome. | Bienvenu T | Genetic testing | 2002 | PMID: 12180070 |
MECP2 gene mutation analysis in Chinese patients with Rett syndrome. | Pan H | European journal of human genetics : EJHG | 2002 | PMID: 12111643 |
MECP2 mutations in Swedish Rett syndrome clusters. | Xiang F | Clinical genetics | 2002 | PMID: 12081725 |
Mutation analysis of MECP2 and clinical characterization in Korean patients with Rett syndrome. | Chae JH | Journal of child neurology | 2002 | PMID: 11913567 |
Mutation analysis in Rett syndrome. | Milunsky JM | Genetic testing | 2001 | PMID: 11960578 |
Preserved speech variants of the Rett syndrome: molecular and clinical analysis. | Zappella M | American journal of medical genetics | 2001 | PMID: 11746022 |
Rett syndrome in Spain: mutation analysis and clinical correlations. | Monrós E | Brain & development | 2001 | PMID: 11738885 |
Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech. | Yamashita Y | Brain & development | 2001 | PMID: 11738864 |
Spectrum of MECP2 mutations in Rett syndrome. | Lee SS | Brain & development | 2001 | PMID: 11738860 |
Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation. | Yamada Y | Human mutation | 2001 | PMID: 11524741 |
MECP2 mutation screening in Swedish classical Rett syndrome females. | Erlandson A | European child & adolescent psychiatry | 2001 | PMID: 11469283 |
DHPLC analysis of the MECP2 gene in Italian Rett patients. | Nicolao P | Human mutation | 2001 | PMID: 11462237 |
MeCP2 mutations in children with and without the phenotype of Rett syndrome. | Hoffbuhr K | Neurology | 2001 | PMID: 11402105 |
Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome. | Inui K | Brain & development | 2001 | PMID: 11376998 |
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 |
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 |
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 |
Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome. | Amano K | Journal of human genetics | 2000 | PMID: 10944854 |
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 |
Deglycosylation of neutral and acidic human colonic mucin. | Bhattacharyya SN | Inflammation | 1990 | PMID: 2323808 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MECP2 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/306280ba-f29e-479c-a220-4d3eb2bc93d9 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5026fbae-0309-4026-8a49-49ac07d7e193 | - | - | - | - |
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Text-mined citations for rs28935468 ...
HelpRecord last updated Jul 29, 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.