ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.-2_15del (p.Met1fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003640344 SCV004460082 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2023-04-23 criteria provided, single submitter clinical testing The MECP2 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001110792.1, and corresponds to NM_004992.3:c.-162_-146del in the primary transcript. This sequence change affects the initiator methionine of the MECP2 mRNA. The next in-frame methionine is located at codon p.Met106. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with clinical features of Rett syndrome (PMID: 34469436). This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Ala2Val) have been determined to be pathogenic (PMID: 19034540, 19365833, 23238081). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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