ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1225G>A (p.Glu409Lys)

gnomAD frequency: 0.00308  dbSNP: rs56268439
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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV000202529 SCV002540719 benign Rett syndrome 2022-05-10 reviewed by expert panel curation The allele frequency of the p.Glu397Lys variant in MECP2 (NM_004992) is 0.393% in European (Non-Finnish) 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). The p.Glu397Lys variant is observed in at least 2 unaffected individuals (PMID 10577905,12384770, RettBASE) (BS2). In summary, the p.Glu397Lys variant in MECP2 is classified as Benign based on the ACMG/AMP criteria applied (BA1, BS2).
Eurofins Ntd Llc (ga) RCV000081194 SCV000113102 benign not specified 2012-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000081194 SCV000170232 benign not specified 2016-07-15 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.
Genetic Services Laboratory, University of Chicago RCV000081194 SCV000247940 likely benign not specified 2017-06-22 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224642 SCV000280649 likely benign not provided 2014-11-26 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV001081987 SCV000556742 benign Severe neonatal-onset encephalopathy with microcephaly 2024-01-29 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000224642 SCV000609420 likely benign not provided 2017-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000716944 SCV000847789 benign History of neurodevelopmental disorder 2014-08-01 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV000202529 SCV001142081 benign Rett syndrome 2019-05-28 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000081194 SCV001476542 benign not specified 2020-04-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002498425 SCV002807850 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 2022-01-26 criteria provided, single submitter clinical testing
Centre for Population Genomics, CPG RCV000202529 SCV004098724 benign 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 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 2.0 (BA1).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000081194 SCV004847542 benign not specified 2018-03-19 criteria provided, single submitter clinical testing The p.Glu397Lys variant in MECP2 is classified as a benign, because It has been has been identified in 0.39% (328/84800) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP), including 131 hemizygous individuals. While it has been reported in individuals with Rett syndrome and has also been reported in ClinVar (Variant ID 95187). However, in one family a second causative variant was identified in a female proband with Rett, while her her unaffected sister and their hemizygous father also carried the p.Glu397Lys variant (Wan 1999). Computational prediction tools and conservation analysis suggest that the p.Glu397Lys variant may not impact the protein. ACMG/AMP Criteria applied: BS1; BP4_Strong; BP2.
RettBASE RCV000081194 SCV000187932 benign not specified 2013-12-05 no assertion criteria provided curation
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000202529 SCV000257517 uncertain significance Rett syndrome 2013-09-04 no assertion criteria provided clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000224642 SCV000804256 benign not provided 2015-04-03 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000081194 SCV001743998 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000081194 SCV001928703 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000081194 SCV001960130 benign not specified no assertion criteria provided clinical testing

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