ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.1157_1200del (p.Leu386fs) (rs63749748)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756326 SCV000884101 pathogenic not provided 2017-07-27 criteria provided, single submitter clinical testing The MECP2 c.1157_1200del; p.Leu386fs variant (rs63749748) has been reported in the literature in several individuals affected with Rett syndrome (Huppke 2000, Khajuria 2009, Vacca 2001, see RettBASE and references therein). It is reported in the ClinVar database as pathogenic (Variation ID: 143372), and is absent from general population databases (1000 Genome Project, Exome Variant Server, Genome Aggregation Database). This variant creates a frameshift and is predicted to result in a truncated protein or absent transcript. Based on the above information, this variant is considered pathogenic. REFERENCES Link to ClinVar database for c.1157_1200del: https://www.ncbi.nlm.nih.gov/clinvar/variation/143372/ Link to RettBASE variation database: http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic Huppke P et al. Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients. Hum Mol Genet. 2000 May 22;9(9):1369-75. Khajuria R et al. Rapid detection of deletions in hotspot C-terminal segment region of MECP2 by routine PCR method: report of two classical Rett syndrome patients of Indian origin. Genet Test Mol Biomarkers. 2009 Apr;13(2):277-80. Vacca M et al. Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females. J Mol Med (Berl). 2001;78(11):648-55.
Athena Diagnostics Inc RCV000170100 SCV000255790 pathogenic Rett syndrome 2015-07-09 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000170100 SCV000247932 pathogenic Rett syndrome 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000473761 SCV000544617 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2017-10-12 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Leu386Glnfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 101 amino acids of the MECP2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Rett syndrome (PMID: 19914908, 17387578, 10814718, 19371229, 22525432).). ClinVar contains an entry for this variant (Variation ID: 143372). Truncating variants that create a premature translational stop signal in the last exon of MECP2 are known to be pathogenic (PMID: 19914908, 16473305) For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,Children's Mercy Hospital and Clinics RCV000170100 SCV000223852 pathogenic Rett syndrome criteria provided, single submitter clinical testing
RettBASE RCV000132897 SCV000187878 pathogenic Angelman syndrome 2012-09-27 no assertion criteria provided curation
RettBASE RCV000170100 SCV000222421 pathogenic Rett syndrome 2012-09-27 no assertion criteria provided curation

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