Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004797612 | SCV005419051 | likely benign | Rett syndrome | 2024-10-30 | reviewed by expert panel | curation | The p.Glu394_Pro405del variant in MECP2 (NM_004992.4) is observed in at least 20 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Glu394_Pro405del variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5). The highest population minor allele frequency of the p.Glu394_Pro405del variant in MECP2 in gnomAD v4.1 is 0.00003691 in European (non-Finnish) population (not sufficient to meet BS1 criteria). In summary, the p.Glu394_Pro405del variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5). |
| Molecular Diagnostics Lab, |
RCV000445565 | SCV000537191 | uncertain significance | not specified | 2015-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000766764 | SCV000582995 | uncertain significance | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | In-frame deletion of 12 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV001267433 | SCV001445614 | uncertain significance | Inborn genetic diseases | 2018-07-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001339351 | SCV001533091 | uncertain significance | Severe neonatal-onset encephalopathy with microcephaly | 2024-02-22 | criteria provided, single submitter | clinical testing | This variant, c.1180_1215del, results in the deletion of 12 amino acid(s) of the MECP2 protein (p.Glu394_Pro405del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs782746707, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 393491). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |