Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV004581816 | SCV005065920 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2019-11-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region (p.Thr442Argfs*30, p.Gln437Alafs*49, p.Glu455Aspfs*32) have been observed in individuals with MECP2-related conditions (PMID: 19914908, 10814718). This suggests that this may be a clinically significant region of the protein. This variant has been observed in individual(s) with clinical features of MECP2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is a gross deletion (c.1239_*863delinsTGC) that includes the final 74 amino acids of exon 4. The 3' end of this event is confined to the 3'UTR of the MECP2 gene. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MECP2 protein. |