Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000168699 | SCV000595751 | uncertain significance | not specified | 2017-05-25 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000766082 | SCV000897557 | uncertain significance | Severe neonatal-onset encephalopathy with microcephaly; Syndromic X-linked intellectual disability Lubs type; X-linked intellectual disability-psychosis-macroorchidism syndrome; Rett syndrome; Autism, susceptibility to, X-linked 3 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001850385 | SCV002143571 | uncertain significance | Severe neonatal-onset encephalopathy with microcephaly | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 338 of the MECP2 protein (p.Thr338Ser). This variant is not present in population databases (gnomAD no frequency). 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: 188500). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MECP2 protein function. 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. |