ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.1244dup (p.Pro415_Glu416insTer)
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.1244dup (p.Pro415_Glu416insTer)
Variation ID: 429893 Accession: VCV000429893.13
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: Xq28 X: 154030619-154030620 (GRCh38) [ NCBI UCSC ] X: 153296070-153296071 (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 Jul 2, 2017 Feb 20, 2024 Dec 6, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.1244dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Pro415_Glu416insTer frameshift NM_004992.4:c.1208dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Pro403_Glu404insTer frameshift NM_001316337.2:c.929dup NP_001303266.1:p.Pro310_Glu311insTer frameshift NM_001369391.2:c.929dup NP_001356320.1:p.Pro310_Glu311insTer frameshift NM_001369392.2:c.929dup NP_001356321.1:p.Pro310_Glu311insTer frameshift NM_001369393.2:c.929dup NP_001356322.1:p.Pro310_Glu311insTer frameshift NM_001369394.2:c.929dup NP_001356323.1:p.Pro310_Glu311insTer frameshift NM_001386137.1:c.539dup NP_001373066.1:p.Pro180_Glu181insTer frameshift NM_001386138.1:c.539dup NP_001373067.1:p.Pro180_Glu181insTer frameshift NM_001386139.1:c.539dup NP_001373068.1:p.Pro180_Glu181insTer frameshift NM_004992.3:c.1208dupC NC_000023.11:g.154030625dup NC_000023.10:g.153296076dup NG_007107.3:g.111484dup LRG_764:g.111484dup LRG_764t1:c.1244dup LRG_764p1:p.Pro415_Glu416insTer LRG_764t2:c.1208dup LRG_764p2:p.Pro403_Glu404insTer - Protein change
- Other names
- NM_001110792.2(MECP2):c.1244dup
- p.Pro415_Glu416insTer
- Canonical SPDI
- NC_000023.11:154030619:GGGGGG:GGGGGGG
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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 | - |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Pathogenic (1) |
criteria provided, single submitter
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Oct 8, 2019 | RCV000493742.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 28, 2021 | RCV001231788.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2016 | RCV001197201.2 | |
Uncertain significance (2) |
reviewed by expert panel
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Dec 6, 2023 | RCV002226465.2 |
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
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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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Uncertain significance
(Dec 06, 2023)
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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
Accession: SCV004175919.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The p.Glu404Ter variant in MECP2 (NM_004992.4) is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene … (more)
The p.Glu404Ter variant in MECP2 (NM_004992.4) is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Glu404Ter variant in MECP2 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with seizures (PMID 29655203) (PM6_Supporting). The allele frequency of the p.Glu416Ter variant in MECP2 is 0.01173% in East Asian sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). In summary, the p.Glu404Ter variant in MECP2 is classified as variant of uncertain significance based on the ACMG/AMP criteria (BS1, PVS1, PM6_Supporting). (less)
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Pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Autism, susceptibility to, X-linked 3
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367838.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PP4,PP5. This variant was detected in hemizygous state.
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Pathogenic
(Oct 08, 2019)
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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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GeneDx
Accession: SCV000582571.4
First in ClinVar: Jul 02, 2017 Last updated: Jul 02, 2017 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29655203) (less)
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Pathogenic
(Mar 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002505558.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Comment:
This variant was identified as hemizygous and inherited from a mother with skewed X-Inactivation._x000D_ Criteria applied: PVS1, PS4_MOD, PM2_SUP
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Pathogenic
(Jun 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Severe neonatal-onset encephalopathy with microcephaly
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001404320.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Gln437Alafs*49) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Gln437Alafs*49) have been determined to be pathogenic (PMID: 10814718, 11055898, 16473305, 19914908, 23696494; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 429893). This premature translational stop signal has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID: 29655203). This variant is present in population databases (rs781843758, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Glu404*) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the MECP2 protein. (less)
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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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Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders. | Lindy AS | Epilepsia | 2018 | PMID: 29655203 |
Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome. | Chapleau CA | American journal of medical genetics. Part A | 2013 | PMID: 23696494 |
Updating the profile of C-terminal MECP2 deletions in Rett syndrome. | Bebbington A | Journal of medical genetics | 2010 | PMID: 19914908 |
Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. | Philippe C | European journal of medical genetics | 2006 | PMID: 16473305 |
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 |
Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients. | Huppke P | Human molecular genetics | 2000 | PMID: 10814718 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/2975ab3b-e66c-4632-81d1-b55b76117bf7 | - | - | - | - |
Text-mined citations for rs781843758 ...
HelpRecord last updated Feb 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.