Submissions for variant NM_001110792.2(MECP2):c.844del (p.Arg282fs)

dbSNP: rs62931162

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000168692	SCV000781708	pathogenic	Rett syndrome	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001008096	SCV001167842	pathogenic	not provided	2023-08-15	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11402105, 16965328, 16473305, 11738864, 10991688, 11055898, 12567420, 15173251, 32472557, 17440498, 15737703, 16832102)
Invitae	RCV000133243	SCV001585670	pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2023-10-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg270Glufs*19) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 217 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with MECP2-related conditions (PMID: 10991688, 16832102, 16965328, 17440498, 21878110). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as '882(C)'. ClinVar contains an entry for this variant (Variation ID: 143702). This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Leu386Glnfs*4) have been determined to be pathogenic (PMID: 10814718, 17387578, 19914908). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003895011	SCV004712436	pathogenic	MECP2-related condition	2024-02-23	criteria provided, single submitter	clinical testing	The MECP2 c.808delC variant is predicted to result in a frameshift and premature protein termination (p.Arg270Glufs*19). This variant has been reported to be causative for Rett syndrome (Ravn et al. 2011. PubMed ID: 21878110; Venâncio et al. 2007. PubMed ID: 17440498) and it occurred de novo in the patient (Ravn et al. 2011. PubMed ID: 21878110). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Other truncating variants in the 5’ and 3’ surrounding region of this variant have been reported to be pathogenic for Rett syndrome (HGMD database; Wan et al. 1999. PubMed ID: 10577905; Philippe et al. 2006. PubMed ID: 16473305). This variant is interpreted as pathogenic.
RettBASE	RCV000133243	SCV000188247	pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2010-08-24	no assertion criteria provided	curation
RettBASE	RCV000168692	SCV000222440	pathogenic	Rett syndrome	2010-08-24	no assertion criteria provided	curation