Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482709 | SCV000566490 | pathogenic | not provided | 2017-02-24 | criteria provided, single submitter | clinical testing | The c.690delA pathogenic variant in the MECP2 gene causes a frameshift starting with codon Glycine 232, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 16 of the new reading frame, denoted p.Gly232AlafsX16. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 255 amino acids of the MECP2 protein are lost and replaced with 15 incorrect amino acids. Although this pathogenic variant has not been previously reported to our knowledge, a different nucleotide change, c.695delG, resulting in the same frameshift variant has been reported multiple times previously in association with Rett syndrome (RettBASE). Therefore, the presence of c.690delA is consistent with the diagnosis of Rett syndrome in this individual. |
| Invitae | RCV002526534 | SCV003219480 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2022-07-09 | 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.Arg255*) have been determined to be pathogenic (PMID: 1241840, 10508514, 17089071, 23270700). 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: 418998). 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.Gly232Alafs*16) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 255 amino acid(s) of the MECP2 protein. |
| Centre de Biologie Pathologie Génétique, |
RCV001251834 | SCV001427576 | pathogenic | Rett syndrome | 2019-01-01 | no assertion criteria provided | clinical testing |