ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.437C>T (p.Ser146Phe) (rs61748390)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255743 SCV000322256 pathogenic not provided 2016-06-30 criteria provided, single submitter clinical testing The de novo S134F pathogenic variant in the MECP2 gene has been reported previously in two unrelated individuals with Rett syndrome (Fukuda et al., 2005; Hadzsiev et al., 2011). In addition, pathogenic missense variants at this same position (S134P and S134C) have been reported in the Human Gene Mutation Database in association with Rett syndrome (Stenson et al., 2014; RettBASE), supporting the functional importance of this region of the protein. The S134F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S134F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the methyl CpG-binding domain (MBD) and is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret S134F as a pathogenic variant.
RettBASE RCV000133096 SCV000188086 uncertain significance Rett syndrome 2011-11-01 no assertion criteria provided curation

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