ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.380C>T (p.Pro127Leu) (rs267608387)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531543 SCV000645664 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2018-09-27 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 127 of the MECP2 protein (p.Pro127Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two individuals affected with classical Rett syndrome (PMID: 16225173, 11960578) and an individual affected with the rare preserved speech variant of Rett syndrome (PMID: 11245712). This variant has also been shown to arise de novo in an individual affected with Rett syndrome (PMID: 20376788, 22182064). ClinVar contains an entry for this variant (Variation ID: 143552). Experimental studies have shown that this this missense change did not affect MECP2 accumulation at chromocenters or MECP2 transcriptional repressive activity in cultured cells (PMID: 21831886, 12843318). For these reasons, this variant has been classified as Pathogenic.
RettBASE RCV000133085 SCV000188074 uncertain significance Rett syndrome 2010-07-13 no assertion criteria provided curation

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