ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.554C>G (p.Pro185Arg)
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.
Uncertain significance(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.554C>G (p.Pro185Arg)
Variation ID: 143609 Accession: VCV000143609.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154031310 (GRCh38) [ NCBI UCSC ] X: 153296761 (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 22, 2015 Feb 28, 2024 Jan 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.554C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Pro185Arg missense NM_004992.4:c.518C>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Pro173Arg missense NM_001316337.2:c.239C>G NP_001303266.1:p.Pro80Arg missense NM_001369391.2:c.239C>G NP_001356320.1:p.Pro80Arg missense NM_001369392.2:c.239C>G NP_001356321.1:p.Pro80Arg missense NM_001369393.2:c.239C>G NP_001356322.1:p.Pro80Arg missense NM_001369394.2:c.239C>G NP_001356323.1:p.Pro80Arg missense NM_001386137.1:c.-128-24C>G intron variant NM_001386138.1:c.-128-24C>G intron variant NM_001386139.1:c.-128-24C>G intron variant NC_000023.11:g.154031310G>C NC_000023.10:g.153296761G>C NG_007107.3:g.110794C>G LRG_764:g.110794C>G LRG_764t1:c.554C>G LRG_764p1:p.Pro185Arg LRG_764t2:c.518C>G LRG_764p2:p.Pro173Arg AJ132917.1:c.518C>G - Protein change
- P173R, P185R, P80R
- Other names
- NM_001110792.2(MECP2):c.554C>G
- p.Pro185Arg
- Canonical SPDI
- NC_000023.11:154031309:G:C
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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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00003
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
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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
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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Uncertain significance (2) |
criteria provided, single submitter
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Mar 4, 2016 | RCV000133149.8 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 9, 2024 | RCV000192592.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 5, 2020 | RCV000686598.6 |
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
(Mar 04, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000247975.2
First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017 |
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Uncertain significance
(Nov 05, 2020)
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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: SCV000814123.3
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in an individual with Rett syndrome as inherited from an unaffected mother with random X-chromosome inactivation, however, that individual also carried another variant that was de novo and in trans(on the opposite chromosome) with this variant (PMID: 23696494). ClinVar contains an entry for this variant (Variation ID: 143609). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 173 of the MECP2 protein (p.Pro173Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. (less)
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Uncertain significance
(Jul 07, 2015)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: no, yes
Allele origin:
maternal,
unknown
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Molecular Diagnostics Lab, Nemours Children's Health, Delaware
Accession: SCV000537173.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
Observation 1:
Number of individuals with the variant: 1
Age: 0-9 years
Sex: female
Observation 2:
Number of individuals with the variant: 1
Age: 30-39 years
Sex: female
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Likely benign
(Jan 09, 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: SCV004232257.1
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 benign. At least the following criteria are met: The variant is observed in at least 1 individual with no features of Rett Syndrome (BS2_Supporting). ( RettBASE, PMID 23696494). The allele frequency of this variant in at least one population in gnomAD is between 0.008% and 0.03% (BS1). (less)
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Uncertain significance
(Feb 15, 2011)
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no assertion criteria provided
Method: curation
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Not specified
Affected status: not provided
Allele origin:
maternal,
unknown
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RettBASE
Accession: SCV000188141.2
First in ClinVar: Aug 17, 2014 Last updated: Apr 22, 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
Sex: female
Tissue: Blood
Comment on evidence:
Not known
Observation 3:
Number of individuals with the variant: 1
Sex: female
Tissue: Blood
Comment on evidence:
Not Rett synd. - unaffected family member
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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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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 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/971d22e4-80db-4324-bae4-bf42676793bd | - | - | - | - |
Text-mined citations for rs267608492 ...
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.