ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1018C>G (p.Leu340Val)

gnomAD frequency: 0.00001  dbSNP: rs267608556
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001372487 SCV001569155 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2023-06-14 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt MECP2 protein function. ClinVar contains an entry for this variant (Variation ID: 143756). This missense change has been observed in individual(s) with clinical features of Rett syndrome (PMID: 16473305). This variant is present in population databases (rs267608556, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 328 of the MECP2 protein (p.Leu328Val).
GeneDx RCV001753520 SCV001985475 uncertain significance not provided 2020-04-16 criteria provided, single submitter clinical testing Previously reported in a female patient with a clinical diagnosis of Rett syndrome, however additional clinical details were not provided (Philippe et al., 2006); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16473305)
Centre for Population Genomics, CPG RCV000133302 SCV004232218 uncertain significance Rett syndrome 2024-01-15 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 3.0, this variant is classified as a variant of uncertain significance. At least the following criteria are met: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2). Has been observed in at least 2 individuals with phenotypes consistent with MECP2-related disease (PS4_Supporting).PMID: 16473305 , ClinVar Variation ID:143756
RettBASE RCV000133302 SCV000188311 uncertain significance Rett syndrome 2008-01-21 no assertion criteria provided curation

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