Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000558865 | SCV000645649 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2017-08-10 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 1 of the MECP2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The MECP2 gene has multiple clinically relevant isoforms. The c.62+1G>A variant occurs in alternate transcript NM_001110792.1, which corresponds to position c.-99+1G>A in NM_004992.3, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Rett syndrome (PMID: 15737703). It is also known as "Ex1 donor site" in the literature. ClinVar contains an entry for this variant (Variation ID: 189776). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MECP2 are known to be pathogenic (PMID: 12180070). For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000170294 | SCV001142097 | pathogenic | Rett syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Rett |
RCV000170294 | SCV000222628 | uncertain significance | Rett syndrome | 2008-02-18 | no assertion criteria provided | curation |