ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.419C>T (p.Ala140Val) (rs28934908)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224266 SCV000281580 pathogenic not provided 2014-08-26 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414791 SCV000492695 likely pathogenic Motor delay; Micrognathia; Hearing impairment; Downslanted palpebral fissures; Microcephaly; Stenosis of the external auditory canal; Intellectual disability; Postnatal growth retardation 2015-09-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224266 SCV000202987 pathogenic not provided 2014-04-10 criteria provided, single submitter clinical testing
GeneReviews RCV000020628 SCV000041141 pathologic Rett syndrome 2012-06-28 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000544176 SCV000645665 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2018-09-22 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 140 of the MECP2 protein (p.Ala140Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature to segregate with neurodevelopmental disorders in several large families (PMID: 11007980, 26350204, 25473036, 27465203, 12325019). ClinVar contains an entry for this variant (Variation ID: 11823). Multiple experimental studies and assays have found no apparent disruption on protein function for the p.Ala140Val missense change (PMID: 12843318, 26418480, 21831886). In summary, this variant is a rare missense change that is absent from the population and observed in affected individuals. While it remains unknown to what effect this missense change impacts protein function, the clinical and genetic evidence indicate this variant segregates with disease. For this reason, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000012596 SCV000782728 pathogenic Mental retardation, X-linked, syndromic 13 2017-09-22 criteria provided, single submitter clinical testing
OMIM RCV000012596 SCV000032831 pathogenic Mental retardation, X-linked, syndromic 13 2002-10-01 no assertion criteria provided literature only
RettBASE RCV000020628 SCV000188092 likely pathogenic Rett syndrome 2016-04-26 no assertion criteria provided research
TIDEX, University of British Columbia RCV000020628 SCV000586832 pathogenic Rett syndrome criteria provided, single submitter research

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