ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.536G>C (p.Arg179Pro)

dbSNP: rs2148663951
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001980568 SCV002274882 likely pathogenic Severe neonatal-onset encephalopathy with microcephaly 2021-05-18 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg167 ‚Äãamino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11309367, 14598336, 27929079, 30083362). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MECP2 protein function. This variant has not been reported in the literature in individuals with MECP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 167 of the MECP2 protein (p.Arg167Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline.
Centre for Population Genomics, CPG RCV005053991 SCV005687566 uncertain significance Rett syndrome 2024-12-02 criteria provided, single submitter curation 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 Uncertain significance. The following criteria are met: Another missense variant in the same codon has been classified as pathogenic (PM5) (ClinVar RCV000193537). At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4) PMID: 34457282. This variant is absent from gnomAD (PM2_Supporting).

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