ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1363G>A (p.Ala455Thr) (rs193922677)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415982 SCV000493588 uncertain significance not provided 2016-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000438624 SCV000513575 likely benign not specified 2016-07-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000438624 SCV000698536 uncertain significance not specified 2016-04-01 criteria provided, single submitter clinical testing Variant Summary: The c.1327G>A variant involves the alteration of a non-conserved nucleotide resulting in substitution of a non-conserved Alanine 443 residue with Threonine in the C-Terminal domain of the MECP2 gene. 4/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.006% (5/87652 chromosomes tested), predominantly in individuals of European descent (0.006% or 3/47913 chromosomes, including 1 presumably healthy adult hemizygous male). The variant was reported in the literature in 2 patients: as a maternally inherited variant in one male patient with nonspecific mental retardation without strong evidence for causality (Zvereff et al, 2012) and in a female patient reportedly diagnosed based on clinical evaluation performed according to the Rett Assessment Rating Scale (RARS) (Isaias et al, 2014). No information about segregation as well as XCI data was available for the patient described by Isias et al. The variant has been reported by the RettBase mutation database as a variant of unknown significance citing the report by Zvereff et al. Based on its prevalence in healthy controls, including one male individual, this variant is unlikely to be associated with the pathophysiology of Rett syndrome. However, its involvement in other types non-syndromic X-linked mental retardation cannot entirely be excluded. Therefore, this variant was classified as a VUS-possibly benign, until more information becomes available.
Invitae RCV001079728 SCV000766866 benign Severe neonatal-onset encephalopathy with microcephaly 2019-12-31 criteria provided, single submitter clinical testing
RettBASE RCV000170261 SCV000222593 uncertain significance Mental retardation, X-linked, syndromic 13 2012-09-27 no assertion criteria provided curation
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251833 SCV001427575 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.