Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000170227 | SCV002769696 | likely pathogenic | Rett syndrome | 2022-10-13 | reviewed by expert panel | curation | The p.Ile293_Ser350del variant in MECP2 (NM_004992.3) causes an in-frame deletion of 58 amino acids in a non-repeat region of MECP2, which results in a deletion of greater than 10% of the total protein length (PM4_strong). The p.Ile293_Ser350del variant occurs in the well-characterized transcription repression functional domain of the MECP2 gene (PM1). The p.Ile293_Ser350del variant has been observed in at least 2 individuals with Rett syndrome or atypical Rett syndrome (PMID 22277191, internal database - Invitae) (PS4_supporting). In summary, the p.Ile293_Ser350del variant in MECP2 is classified as Likely Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PM4_strong, PM1, PS4_supporting). |
Invitae | RCV001298644 | SCV001487707 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2023-07-14 | criteria provided, single submitter | clinical testing | This variant, c.871_1044del, results in the deletion of 58 amino acid(s) of the MECP2 protein (p.Ile293_Ser350del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with atypical Rett syndrome (PMID: 22277191). ClinVar contains an entry for this variant (Variation ID: 189732). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Pro302His) have been determined to be pathogenic (PMID: 10944854, 15737703, 16225173). 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. |
Rett |
RCV000170227 | SCV000222557 | pathogenic | Rett syndrome | 2012-09-27 | no assertion criteria provided | curation |