Submissions for variant NM_001110792.2(MECP2):c.638C>T (p.Ala213Val)

gnomAD frequency: 0.00150  dbSNP: rs61748381

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000202489	SCV002540676	benign	Rett syndrome	2022-05-10	reviewed by expert panel	curation	The allele frequency of the p.Ala201Val (NM_004992) variant in MECP2 is 1.045% in East Asian sub population in gnomAD, which is high enough to be classified as Benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). In summary, the p.Ala201Val variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1).
GeneDx	RCV000153477	SCV000170220	benign	not specified	2016-06-17	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.
Eurofins Ntd Llc (ga)	RCV000153477	SCV000202984	benign	not specified	2014-04-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000153477	SCV000247981	benign	not specified	2013-06-05	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224215	SCV000281574	benign	not provided	2015-02-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083234	SCV000556752	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-02-01	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000202489	SCV000746807	likely benign	Rett syndrome	2017-12-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000717310	SCV000848159	benign	History of neurodevelopmental disorder	2016-07-07	criteria provided, single submitter	clinical testing	Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Co-occurence with mutation in same gene (phase unknown);Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Institute of Human Genetics, University of Leipzig Medical Center	RCV001083234	SCV001440877	benign	Severe neonatal-onset encephalopathy with microcephaly	2019-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498620	SCV002797283	likely benign	Severe neonatal-onset encephalopathy with microcephaly; Syndromic X-linked intellectual disability Lubs type; X-linked intellectual disability-psychosis-macroorchidism syndrome; Rett syndrome; Autism, susceptibility to, X-linked 3	2022-04-25	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000224215	SCV004220015	benign	not provided	2023-06-12	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV000202489	SCV004808874	benign	Rett syndrome	2024-03-22	criteria provided, single submitter	curation	This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 3.0 (BA1).
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001083234	SCV005086733	benign	Severe neonatal-onset encephalopathy with microcephaly	2023-07-17	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Encephalopathy, neonatal severe (MIM#300673). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of disease. (SB) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Breakthrough Genomics, Breakthrough Genomics	RCV000224215	SCV005206921	likely benign	not provided		criteria provided, single submitter	not provided
RettBASE	RCV000153477	SCV000188167	benign	not specified	2013-06-12	no assertion criteria provided	curation
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000202489	SCV000257513	pathogenic	Rett syndrome	2012-08-17	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000224215	SCV001744278	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000224215	SCV001800252	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000153477	SCV001929517	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000224215	SCV001972809	likely benign	not provided		no assertion criteria provided	clinical testing