ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.1193_*944del (p.Leu398fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.1193_*944del (p.Leu398fs)
Variation ID: 189661 Accession: VCV000189661.2
- Type and length
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Deletion, 1,249 bp
- Location
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Cytogenetic: Xq28 X: 154029423-154030671 (GRCh38) [ NCBI UCSC ] X: 153294874-153296122 (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 Feb 28, 2024 Jan 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.1193_*944del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Leu398fs frameshift NM_004992.4:c.1157_*944del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Leu386fs frameshift NM_001316337.2:c.878_*944del NP_001303266.1:p.Leu293fs frameshift NM_001369391.2:c.878_*944del NP_001356320.1:p.Leu293fs frameshift NM_001369392.2:c.878_*944del NP_001356321.1:p.Leu293fs frameshift NM_001369393.2:c.878_*944del NP_001356322.1:p.Leu293fs frameshift NM_001369394.2:c.878_*944del NP_001356323.1:p.Leu293fs frameshift NM_001386137.1:c.488_*944del NP_001373066.1:p.Leu163fs frameshift NM_001386138.1:c.488_*944del NP_001373067.1:p.Leu163fs frameshift NM_001386139.1:c.488_*944del NP_001373068.1:p.Leu163fs frameshift NM_004992.3:c.1157_*944del1249 NC_000023.11:g.154029424_154030672del NC_000023.10:g.153294875_153296123del NG_007107.3:g.111433_112681del LRG_764:g.111433_112681del LRG_764t1:c.1193_*944del LRG_764p1:p.Leu398fs LRG_764t2:c.1157_*944del LRG_764p2:p.Leu386fs - Protein change
- L398fs, L293fs, L386fs, L163fs
- Other names
- NM_001110792.2(MECP2):c.1193_*944del
- p.Leu398fs
- Canonical SPDI
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MECP2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1824 | 2145 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (2) |
criteria provided, single submitter
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Jan 15, 2024 | RCV000170145.3 |
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
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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
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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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Likely pathogenic
(Jan 15, 2024)
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criteria provided, single submitter
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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Centre for Population Genomics, CPG
Accession: SCV004232195.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert … (more)
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD (PM2_Supporting). (less)
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Pathogenic
(Jan 21, 2008)
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no assertion criteria provided
Method: curation
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Rett syndrome
Affected status: yes
Allele origin:
unknown
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RettBASE
Accession: SCV000222473.1
First in ClinVar: Apr 24, 2015 Last updated: Apr 24, 2015 |
Number of individuals with the variant: 1
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - not certain
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. | Philippe C | European journal of medical genetics | 2006 | PMID: 16473305 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/4f8e7ae6-abb8-4afc-a75b-256c8ace54ba | - | - | - | - |
Text-mined citations for this variant ...
HelpRecord last updated Feb 28, 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.