Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001381823 | SCV001580347 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2020-05-02 | criteria provided, single submitter | clinical testing | This variant is a complex sequence change that results in the deletion of exon 3 and part of exon 4 and the insertion of 184 nucleotides (c.27-4824_1121delins184) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant has been observed in individual(s) with clinical features of MECP2-related conditions (Invitae). Similar partial deletions have been reported in individuals with Rett syndrome (PMID: 14974082, 15737703). This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region have been determined to be pathogenic (PMID: 23696494, 10814718, 19914908, 16473305). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |