Submissions for variant NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)

dbSNP: rs28935468

Total submissions: 47

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000012597	SCV001711972	pathogenic	Rett syndrome	2021-03-26	reviewed by expert panel	curation	The p.Arg306Cys variant in MECP2 has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 individuals with Rett Syndrome (PMID 10577905, 11309679, 19189931; internal database, GeneDx) (PS2_very strong). This variant has been observed in at least 4 other individuals with Rett syndrome (PMID 24511209, 23238081, RettBase) (PS4). The p.Arg306Cys variant occurs in the well-characterized transcriptional repression domain (TRD) functional domain of MECP2 (PMID 21326358, 23770565) (PM1). This variant is absent in gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, p.Arg306Cys variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2_very strong, PS4, PM1, PM2_supporting, PP3).
GeneDx	RCV000081218	SCV000190987	pathogenic	not provided	2020-04-16	criteria provided, single submitter	clinical testing	Published functional studies demonstrate that the R306C variant results in a damaging effect (Heckman et al., 2014; Kruusvee et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23770565, 11058114, 27428650, 26647311, 28212680, 32393352, 24511209, 10577905, 23770587, 23238081, 24970834, 24916645, 28348241, 19309283, 16077729, 26175308, 17276711, 11738864, 28394482, 29655203, 30792901, 31139143, 31095231, 25762136, 30577886, 12030010, 31130284, 33278787)
Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics	RCV000012597	SCV000223842	pathogenic	Rett syndrome		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000081218	SCV000230267	pathogenic	not provided	2015-02-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000012597	SCV000248005	pathogenic	Rett syndrome	2013-02-08	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV000224156	SCV000281744	pathogenic	Intellectual disability	2014-07-25	criteria provided, single submitter	clinical testing
Invitae	RCV000466020	SCV000544613	pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the MECP2 protein (p.Arg306Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Rett syndrome (RTT) and accounts for approximately 5% of all classical RTT cases (PMID: 10991688, 11214906, 14649554, 16473305, 24511209). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11824). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MECP2 protein function. Experimental studies have shown that this missense change affects MECP2 function (PMID: 23770565, 23770587, 24970834, 26647311). This variant disrupts the p.Arg306 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10767337, 14649554, 16473305). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000081218	SCV000610040	pathogenic	not provided	2017-08-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000012597	SCV000698547	pathogenic	Rett syndrome	2017-05-11	criteria provided, single submitter	clinical testing	Variant summary: The MECP2 c.916C>T (p.Arg306Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional studies showed that this variant decreased microtubule (MT) stability and down-regulated GRID1, a gene in the neurotransmitter pathway which is known to be down-regulated in the absence of functional MECP2 (Delepine_FEBSL_2013, Livide_EJHG_2014). In addition, a study using the Mecp2R306C mouse knock-out model recapitulated RTT-like features, such as compromised mobility and motor coordination and reduction in brain weight (Lyst_Natneurosci_2013). This variant is absent in 87936 control chromosomes including broad and large populations from ExAC. This variant was reported in numerous patients with RTT syndrome (Buyse_AJHG_2000, Obata_JMG_2000, Xiang_JMG_2000), including instances of de novo occurrence and it is considered the second most common RTT-causing missense mutation. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000012597	SCV000781714	pathogenic	Rett syndrome	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000081218	SCV000884099	pathogenic	not provided	2020-12-24	criteria provided, single submitter	clinical testing	The MECP2 c.916C>T; p.Arg306Cys variant (rs28935468) is a recurrent alteration in individuals diagnosed with Rett syndrome, and often found as a de novo change (Cheadle 2000, Wan 1999, RettBase). Transgenic mice expressing the variant protein show developmental and behavioral phenotypes reminiscent of the clinical symptoms found in human patients (Brown 2016, Heckman 2014). Functional characterization of the MECP2 variant protein indicates disruption in its association with co-repressors, such as HDAC3 and the NCoR complex (Ebert 2013, Heckman 2014, Lyst 2013), and reduction in in-vivo DNA occupancy (Heckman 2014). This results in a failure of the MECP2 protein in mediating transcriptional repression at its targets (Ebert 2013, Lyst 2013). Another missense variant at this residue, p.Arg306His, has also been implicated in Rett syndrome (Cheadle 2000, RettBase). The p.Arg306Cys variant is listed as pathogenic in ClinVar (Variation ID: 11824), and is not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). Based on the above information, the p.Arg306Cys variant is classified as pathogenic. References: RettBase: http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic Brown K et al. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome. Hum Mol Genet. 2016; 25(3):558-70. Cheadle J et al. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet. 2000; 9(7):1119-29. Ebert D et al. Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR. Nature. 2013; 499(7458):341-5. Heckman L et al. Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife. 2014 Jun 26; 3. Lyst M et al. Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor. Nat Neurosci. 2013; 16(7):898-902. Wan M et al. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet. 1999; 65(6):1520-9.
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV000081218	SCV000920485	pathogenic	not provided	2018-05-15	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000012597	SCV000928372	pathogenic	Rett syndrome	2018-07-09	criteria provided, single submitter	clinical testing	PS4, PM1, PM2, PM5, PP3, PP4, PP5
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV000012597	SCV000994545	pathogenic	Rett syndrome	2016-06-29	criteria provided, single submitter	clinical testing
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	RCV000012597	SCV000999382	pathogenic	Rett syndrome		criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000012597	SCV001426148	pathogenic	Rett syndrome	2018-06-27	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000012597	SCV001426580	pathogenic	Rett syndrome		criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000012597	SCV001440007	pathogenic	Rett syndrome	2019-01-01	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000012597	SCV001445896	pathogenic	Rett syndrome	2019-07-26	criteria provided, single submitter	clinical testing	This variant is also referred to in the literature as c.916C>T (p.Arg306Cys) due to use of a different reference transcript (NM_004992.3). This variant is a recurrent alteration that has been reported in multiple individuals with Rett syndrome (PMID: 10577905, 26175308, 29655203, 30792901, 11738864, 19309283, 28394482). RettBASE, a MECP2 variation database, reports the p.Arg318Cys change accounts for approximately 5% of Rett syndrome diagnoses (http://mecp2.chw.edu.au/) (PMID: 28544139). This variant has also been reported as Pathogenic by multiple clinical diagnostic laboratories in the ClinVar database (Variation ID: 11824). Functional studies have shown this missense variant disrupts the ability of the MeCP2 protein to associate with co-repressors (PMID: 23770587, 23770565, 24970834), impairs DNA-binding in vivo and in vitro (PMID: 26647311, 11058114), and results in decreased microtubule stability (PMID: 23238081). The c.952C>T (p.Arg318Cys) variant is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. It affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.952C>T (p.Arg318Cys) variant is classified as Pathogenic.
Baylor Genetics	RCV000012597	SCV001524905	pathogenic	Rett syndrome	2019-08-09	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV000081218	SCV002017252	pathogenic	not provided	2023-07-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000081218	SCV002063366	pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	MECP2: PS2, PS4, PM2, PP3
Suma Genomics	RCV000012597	SCV002097337	pathogenic	Rett syndrome		criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV001841244	SCV002102399	pathogenic	Autism, susceptibility to, X-linked 3	2021-11-01	criteria provided, single submitter	research	A heterozygous missense variation in exon 3 of the MECP2 gene that results in the amino acid substitution of Cysteine for Arginine at codon 318 was detected. The observed variant c.952C>T (p.Arg318Cys) has not been reported in the 1000 genomes and gnomAD databases. The in-silico predictions of the variant are damaging by PolyPhen-2 (HumDiv), SIFT, LRT and MutationTaster2. The reference codon is conserved across species. This variant has previously been reported in patients affected with Rett syndrome. Segregation analysis showed the variant to be of de novo origin. In summary, the variant meets our criteria to be classified as a pathogenic variant.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV002273927	SCV002558995	pathogenic	Neurodevelopmental delay		criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV002287332	SCV002578069	pathogenic	See cases	2019-01-23	criteria provided, single submitter	clinical testing	ACMG categories: PS2,PM2,PM5,PP3,PP4,PP5
Ambry Genetics	RCV002444428	SCV002683250	pathogenic	Inborn genetic diseases	2018-12-06	criteria provided, single submitter	clinical testing	The p.R306C pathogenic mutation (also known as c.916C>T), located in coding exon 3 of the MECP2 gene, results from a C to T substitution at nucleotide position 916. The arginine at codon 306 is replaced by cysteine, an amino acid with highly dissimilar properties. This mutation has been observed in multiple individuals with Rett syndrome, both inherited and de novo occurrences (Wan M et al. Am. J. Hum. Genet., 1999 Dec;65:1520-9; Buyse IM et al. Am. J. Hum. Genet., 2000 Dec;67:1428-36; Yamashita Y et al. Brain Dev., 2001 Dec;23 Suppl 1:S157-60; Heilstedt HA et al. Am. J. Med. Genet., 2002 Aug;111:238-42; Schanen C et al. Am. J. Med. Genet. A, 2004 Apr;126A:129-40; Zhang Q et al. Am. J. Med. Genet. B Neuropsychiatr. Genet., 2017 Jun;174:451-457). Functional studies demonstrated that this alteration had decreased microtubule stability, abolished the interaction of MeCP2 with the NCoR/SMRT co-repressor, and down regulated GRID1 expression (Delépine C et al. FEBS Lett., 2013 Jan;587:245-53; Lyst MJ et al. Nat. Neurosci., 2013 Jul;16:898-902; Livide G et al. Eur. J. Hum. Genet., 2015 Feb;23:195-201). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000081218	SCV002774385	pathogenic	not provided	2023-05-12	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in multiple individuals affected with Rett syndrome (PMIDs: 10767337 (2000), 10814719 (2000), 23238081 (2013), and 24511209 (2014)), and has been reported in multiple symptomatic individuals as a de novo occurrence (PMIDs: 10577905 (1999), 11309679 (2001), 19189931 (2009), and 32393352 (2020)). In addition, functional studies report this variant is damaging to MECP2 protein function (PMIDs: 23770565 (2013), 23770587 (2013), 24970834 (2014), and 26647311 (2016)). Based on the available information, this variant is classified as pathogenic.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000012597	SCV002820191	pathogenic	Rett syndrome		criteria provided, single submitter	clinical testing	The missense variant p.R306C in MECP2 (NM_004992.4) has been previously reported in at least 4 individuals affected with Rett syndrome (Cortelazzo et al, 2014). Experimental studies have shown that this missense change abolishes the interaction between MECP2 and its co-repressor and impairs DNA-binding both in vitro and in vivo (Lyst et al, 2013; Heckman et al. 2014). The p.R306C variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a large physicochemical difference between arginine and cysteine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The p.R306C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 306 of MECP2 is conserved in all mammalian species. The nucleotide c.916 in MECP2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic
3billion	RCV000012597	SCV003841464	pathogenic	Rett syndrome	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID: 34837432). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.84; 3Cnet: 0.82). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000011824). The variant has been previously reported as de novo in at least two similarly affected unrelated individuals (PMID: 10577905, 11309679, 19189931). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 2323808, 24511209). Different missense changes at the same codon (p.Arg318His, p.Arg318Leu, p.Arg318Pro) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000143746, VCV000143747, VCV000521860). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224093	SCV003920185	pathogenic	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	2021-03-30	criteria provided, single submitter	clinical testing	MECP2 NM_004992.3 exon4 p.Arg306Cys (c.916C>T): This variant is one of the most common pathogenic variants in MECP2 and has been reported in the literature in several individuals with Rett syndrome incliuding at least two de novo occurrences (Wan 1999 PMID: 10577905; Yamashita 2001 PMID: 11738864, Jian 2005 PMID: 16077729; Voutoufianakis 2007 PMID: 17276711; Fendri-Kriaa 2009; PMID: 19309283; Delepine 2013 PMID: 23238081; Cortelazzo 2014 PMID: 24511209; Livide 2015 PMID: 24970834; Pidcock 2016 PMID: 26175308; Zhang 2017 PMID: 28394482; Lindy 2018 29655203; Long 2019 31139143; Scocchia 2019 30792901). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID: 11824). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Additionally, both in vitro and in vivo functional studies have shown a deleterious effect for this variant (Delepine 2013 PMID: 23238081; Ebert 2013 PMID: 23770587; Lyst 2013 PMID: 23770656; Heckman 2014 PMID: 24970834; Livide 2015 PMID: 24970834; Brown 2016 PMID: 26647311). However, these studies may not accurately represent in vivo human biological function. In summary, this variant is classified as pathogenic based on the data above.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000012597	SCV003935869	pathogenic	Rett syndrome	2019-12-18	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV000012597	SCV004098728	pathogenic	Rett syndrome	2023-08-14	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 2.0, this variant is classified as pathogenic. At least the following criteria are met: This variant has been identified as a de novo occurrence with confirmed parental relationships in at least 2 individuals with Rett syndrome , or in at least 1 individual with confirmed parental relationships AND assumed the novo in at least 2 individuals with unconfirmed parental relationships (PS2_Very_Strong). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). Occurs in the well-characterized Transcriptional repression domain (TRD) of MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact (REVEL score ≥ 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting).
Athena Diagnostics Inc	RCV000081218	SCV004229773	pathogenic	not provided	2023-05-12	criteria provided, single submitter	clinical testing	This variant has been identified in multiple unrelated individuals with Rett syndrome and occurs de novo in multiple individuals. This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) In some published literature, this variant is referred to as c.990C>T and c.991C>T. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 23770565, 24970834, 23770587, 26647311) The variant is located in a region that is considered important for protein function and/or structure.
PreventionGenetics, part of Exact Sciences	RCV003924825	SCV004745453	pathogenic	MECP2-related condition	2024-01-12	criteria provided, single submitter	clinical testing	The MECP2 c.916C>T variant is predicted to result in the amino acid substitution p.Arg306Cys. This variant has been reported to be causative for Rett Syndrome (Wan et al. 1999. PubMed ID: 10577905; Aldosary et al. 2020. PubMed ID: 32105570; OMIM: #312750). The pathogenicity of this recurrent variant is supported by functional studies, as well as its presence in numerous affected individuals (Brown et al. 2016. PubMed ID: 26647311). Some studies indicate a favorable outcome with increased mobility and delayed regression resulting from this change, in comparison to other pathogenic MECP2 variants (Schanen et al. 2004. PubMed ID: 15057977; Pidcock et al. 2016. PubMed ID: 26175308). While more than 99% of pathogenic MECP2 variants occur de novo in the affected patient, at least one case of maternal transmission is reported for the p.Arg306Cys missense change (Wan et al. 1999. PubMed ID: 10577905). Variably skewed X-chromosome inactivation is predicted to underlie the range of phenotypic severity observed in individuals with this change (Wan et al. 1999. PubMed ID: 10577905). Of note, other missense variants affecting the same amino acid (p.Arg306His, p.Arg306Pro, p.Arg306Leu) have also been reported to be pathogenic for Rett syndrome (HGMD database; Cheadle et al. 2000. PubMed ID: 10767337). Taken together, we interpret this variant as pathogenic.
Illumina Laboratory Services, Illumina	RCV000012597	SCV004801532	pathogenic	Rett syndrome	2017-08-10	criteria provided, single submitter	clinical testing	The MECP2 c.916C>T p.(Arg306Cys) missense variant has been reported in at least six studies in which it was found in a total of 39 individuals with Rett syndrome (Wan et al. 1999; Bourdon et al. 2001; Schanen et al. 2004; Li et al. 2007; Cortelazzo et al. 2014; Pidcock et al. 2016). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies in patient fibroblasts and cultured cortical neurons, demonstrated that the p.(Arg306Cys) variant protein resulted in almost total depolymerization of microtubules under the effect of cold-induced stress and also rendered the variant protein incapable of interacting with the nuclear receptor co-repressor complex as compared with wildtype protein (Delépine et al. 2013; Ebert et al. 2013). In addition, transgenic mice expressing the p.(Arg306Cys) variant protein recapitulated many of the phenotypes seen in affected individuals (Heckman et al. 2014; Brown et al. 2015). Based on the collective evidence, the c.916C>T p.(Arg306Cys) variant is classified as pathogenic for Rett syndrome.
OMIM	RCV000012597	SCV000032832	pathogenic	Rett syndrome	2004-04-15	no assertion criteria provided	literature only
RettBASE	RCV000012597	SCV000188298	pathogenic	Rett syndrome	2014-02-26	no assertion criteria provided	curation
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000012597	SCV000257515	pathogenic	Rett syndrome	2014-06-26	no assertion criteria provided	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000202468	SCV000257516	pathogenic	Angelman syndrome	2006-02-20	no assertion criteria provided	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000081218	SCV000804261	pathogenic	not provided	2015-04-03	no assertion criteria provided	clinical testing
GeneReviews	RCV000012597	SCV000998927	not provided	Rett syndrome		no assertion provided	literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000081218	SCV001808047	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000081218	SCV001932221	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081218	SCV001955633	pathogenic	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000081218	SCV001978724	pathogenic	not provided		no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000012597	SCV004101072	pathogenic	Rett syndrome	2023-11-02	no assertion criteria provided	clinical testing