Submissions for variant NM_001110792.2(MECP2):c.411C>A (p.Ile137=)

gnomAD frequency: 0.00059  dbSNP: rs146107517

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002260608	SCV002540718	benign	Rett syndrome	2022-05-10	reviewed by expert panel	curation	The allele frequency of the p.Ile125= variant in MECP2 (NM_004992) is 0.394% in South 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). The p.Ile125= variant is observed in at least 2 unaffected individuals (PMID 11055898, 20479760, RettBASE proband id 4623, 4624) (BS2). In summary, the p.Ile125= variant in MECP2 is classified as Benign based on the ACMG/AMP criteria applied (BA1, BS2).
Eurofins Ntd Llc (ga)	RCV000081201	SCV000113109	benign	not specified	2013-09-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000081201	SCV000170216	benign	not specified	2013-05-01	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	RCV000081201	SCV000247965	benign	not specified	2018-04-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000081201	SCV000310760	benign	not specified		criteria provided, single submitter	clinical testing
Invitae	RCV001087820	SCV000556728	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000712283	SCV000842733	benign	not provided	2017-11-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000716805	SCV000847649	likely benign	History of neurodevelopmental disorder	2016-08-19	criteria provided, single submitter	clinical testing	Synonymous alterations with insufficient evidence to classify as benign
CeGaT Center for Human Genetics Tuebingen	RCV000712283	SCV001150519	uncertain significance	not provided	2016-10-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000081201	SCV003800987	benign	not specified	2023-01-25	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV002260608	SCV004808977	benign	Rett syndrome	2024-03-08	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).
RettBASE	RCV000081201	SCV000188072	benign	not specified	2011-11-01	no assertion criteria provided	curation
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000081201	SCV000257508	benign	not specified	2007-05-09	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000712283	SCV001930665	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000712283	SCV001965926	likely benign	not provided		no assertion criteria provided	clinical testing