Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001507069 | SCV001712042 | uncertain significance | Rett syndrome | 2021-03-26 | reviewed by expert panel | curation | The p.Thr99Pro variant in MECP2 occurs in the well-characterized methyl-DNA binding (MDB) functional domain of the MECP2 gene (PMID 21326358) (PM1). This variant has been reported in an individual with a clinical phenotype suggestive of Rett Syndrome (internal database) (PP4). The p.Thr99Pro variant is absent from gnomAD (PM2_supporting). In summary, the p.Thr99Pro variant in MECP2 is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (PM1, PM2_supporting, PP4). |
Labcorp Genetics |
RCV001065758 | SCV001230739 | uncertain significance | Severe neonatal-onset encephalopathy with microcephaly | 2019-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with proline at codon 99 of the MECP2 protein (p.Thr99Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MECP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |