ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.353G>A (p.Arg118Gln)
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.
Pathogenic(3); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001110792.2(MECP2):c.353G>A (p.Arg118Gln)
Variation ID: 143534 Accession: VCV000143534.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: Xq28 X: 154032267 (GRCh38) [ NCBI UCSC ] X: 153297718 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 6, 2024 Mar 26, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001110792.2:c.353G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Arg118Gln missense NM_004992.4:c.317G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Arg106Gln missense NM_001316337.2:c.38G>A NP_001303266.1:p.Arg13Gln missense NM_001369391.2:c.38G>A NP_001356320.1:p.Arg13Gln missense NM_001369392.2:c.38G>A NP_001356321.1:p.Arg13Gln missense NM_001369393.2:c.38G>A NP_001356322.1:p.Arg13Gln missense NM_001369394.2:c.38G>A NP_001356323.1:p.Arg13Gln missense NM_001386137.1:c.-244G>A 5 prime UTR NM_001386138.1:c.-244G>A 5 prime UTR NM_001386139.1:c.-244G>A 5 prime UTR NC_000023.11:g.154032267C>T NC_000023.10:g.153297718C>T NG_007107.3:g.109837G>A LRG_764:g.109837G>A LRG_764t1:c.353G>A LRG_764p1:p.Arg118Gln LRG_764t2:c.317G>A LRG_764p2:p.Arg106Gln P51608:p.Arg106Gln AJ132917.1:c.317G>A - Protein change
- R106Q, R118Q, R13Q
- Other names
- NM_001110792.2(MECP2):c.353G>A
- p.Arg118Gln
- Canonical SPDI
- NC_000023.11:154032266:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
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. |
---|---|---|---|---|
Pathogenic (2) |
criteria provided, single submitter
|
Nov 3, 2023 | RCV000133067.6 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 25, 2023 | RCV001542086.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 20, 2023 | RCV003333738.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 26, 2024 | RCV003989324.1 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Jul 20, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Laboratoire Génétique Moléculaire, CHRU TOURS
Accession: SCV001760756.1
First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021 |
Clinical Features:
Intellectual disability (present)
|
|
Pathogenic
(Mar 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV004036376.1
First in ClinVar: Sep 30, 2023 Last updated: Sep 30, 2023 |
Comment:
Published functional studies demonstrate a damaging effect with severely impaired heterochromatin binding (Kudo et al., 2003); In silico analysis supports that this missense variant has … (more)
Published functional studies demonstrate a damaging effect with severely impaired heterochromatin binding (Kudo et al., 2003); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32472557, 10814719, 26418480, 32105570, 12843318, 21831886) (less)
|
|
Pathogenic
(Jan 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Rett syndrome
X-linked intellectual disability-psychosis-macroorchidism syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Accession: SCV004032461.2
First in ClinVar: Sep 09, 2023 Last updated: Oct 14, 2023 |
|
|
Pathogenic
(Nov 03, 2023)
|
criteria provided, single submitter
Method: curation
|
Rett syndrome
Affected status: unknown
Allele origin:
germline
|
Centre for Population Genomics, CPG
Accession: SCV004101629.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 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 … (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 in =2 individuals with Rett syndrome without confirmation of paternity and maternity (PM6_strong, PMID: 11055898, 17089071). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4, PMID: 10814719, 11055898, 16473305, RettBASE internal database). Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain 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)
|
|
Uncertain significance
(Mar 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Syndromic X-linked intellectual disability Lubs type
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806620.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
|
|
Pathogenic
(Nov 01, 2011)
|
no assertion criteria provided
Method: curation
|
Rett syndrome
Affected status: yes, unknown
Allele origin:
unknown,
germline,
de novo
|
RettBASE
Accession: SCV000188055.2
First in ClinVar: Aug 17, 2014 Last updated: Apr 24, 2015 |
Observation 1:
Number of individuals with the variant: 1
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:
Rett syndrome - not certain
Observation 3:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 4:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 5:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 6:
Number of individuals with the variant: 1
Sex: female
Comment on evidence:
Rett syndrome - Not certain
Observation 7:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - Classical
Observation 8:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Classical
Observation 9:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Not known
Comment on evidence:
Rett syndrome - Not certain
Observation 10:
Number of individuals with the variant: 1
Family history: No
Sex: female
Comment on evidence:
Rett syndrome - Classical
Observation 11:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 12:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Blood
Comment on evidence:
Rett syndrome - Not certain
Observation 13:
Number of individuals with the variant: 1
Family history: Yes
Sex: female
Tissue: Not known
Comment on evidence:
Rett syndrome - Not certain
Observation 14:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 15:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 16:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 17:
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
Observation 18:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
Observation 19:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
|
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 |
---|---|---|---|---|
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 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 |
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 |
Spectrum of MECP2 mutations in Rett syndrome. | Bienvenu T | Genetic testing | 2002 | PMID: 12180070 |
The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome. | Ishii T | Brain & development | 2001 | PMID: 11738865 |
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 |
MECP2 mutations account for most cases of typical forms of Rett syndrome. | Bienvenu T | Human molecular genetics | 2000 | PMID: 10814719 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/fec3ca2d-408f-412f-95ad-bf2259d549d1 | - | - | - | - |
Text-mined citations for rs61754457 ...
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.