Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV000660654 | SCV000782782 | pathogenic | Rett syndrome | 2018-02-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000702922 | SCV000831799 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2022-12-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Pro389*, p.Leu386Hisfs*5) have been determined to be pathogenic (PMID: 16473305, 19914908). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 548031). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val380Argfs*13) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 107 amino acid(s) of the MECP2 protein. |
Gene |
RCV001009240 | SCV001169061 | pathogenic | not provided | 2019-08-14 | criteria provided, single submitter | clinical testing | The c.1137dupC variant in the MECP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1137dupC variant causes a frameshift starting with codon Valine 380, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Val380ArgfsX13. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1137dupC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1137dupC as a pathogenic variant. |
Mendelics | RCV002249391 | SCV002517593 | pathogenic | X-linked intellectual disability-psychosis-macroorchidism syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing |