ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.136_139del (p.Asp46fs)

dbSNP: rs61754428
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219819 SCV001391777 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2022-04-01 criteria provided, single submitter clinical testing 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.Arg255*) have been determined to be pathogenic (PMID: 1241840, 10508514, 17089071, 23270700). 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: 143304). This variant is also known as 100del4. This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 11524741). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp34Argfs*90) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 453 amino acid(s) of the MECP2 protein.
Centre for Population Genomics, CPG RCV000132828 SCV004101568 pathogenic Rett syndrome 2023-10-09 criteria provided, single submitter curation 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 is absent from gnomAD (PM2_Supporting). Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4, PMID: 11524741).
RettBASE RCV000132828 SCV000187805 pathogenic Rett syndrome 2002-09-05 no assertion criteria provided curation

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