ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1193_1224del (p.Leu398fs) (rs267608585)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001035576 SCV001198909 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2019-03-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Leu386Argfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 101 amino acids of the MECP2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Rett syndrome (PMID: 19914908, 21160487, 11746022, 12075485). This variant is also known as c.1157_1188del32 and 1157del32 in the literature. ClinVar contains an entry for this variant (Variation ID: 143366). For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000168702 SCV001430670 pathogenic Rett syndrome 2020-07-16 criteria provided, single submitter clinical testing This MECP2 variant (rs267608585) is absent in a large population dataset and has an entry in ClinVar. This variant has been reported in patients with classic and variant forms of Rett syndrome. This 32-bp deletion results in a frameshift that is predicted to lead to a premature stop codon (PTC) in the last exon of the gene, likely escaping nonsense-mediated decay and resulting in a truncated protein product. This variant is located within a hotspot of deletions in the C-terminus of the MeCP2 protein, which represent ~12% of disease-associated variants in MECP2. We consider it to be pathogenic.
RettBASE RCV000168702 SCV000187872 pathogenic Rett syndrome 2011-11-01 no assertion criteria provided curation

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