Submissions for variant NM_001110792.2(MECP2):c.1198C>T (p.Pro400Ser)

gnomAD frequency: 0.00006  dbSNP: rs61753000

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000169943	SCV002047369	benign	Rett syndrome	2021-12-22	reviewed by expert panel	curation	The allele frequency of the p.Pro388Ser (NM_004992.3) variant in MECP2 is 0.039% in a 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.Pro388Ser variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BA1).
GeneDx	RCV000726321	SCV000190996	likely benign	not provided	2020-11-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 12567420, 27884173, 25969726, 17387578, 19253388, 12872250)
Eurofins Ntd Llc (ga)	RCV000726321	SCV000343777	uncertain significance	not provided	2016-08-17	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000169943	SCV000803542	benign	Rett syndrome	2024-05-15	criteria provided, single submitter	curation	This variant is classified as Benign for Rett syndrome in accordance with classification by the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078768	SCV001009932	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-18	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001257761	SCV001434573	likely benign	Intellectual disability	2020-04-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002515928	SCV003755981	likely benign	Inborn genetic diseases	2022-06-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Centre for Population Genomics, CPG	RCV000169943	SCV004098752	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).
CeGaT Center for Human Genetics Tuebingen	RCV000726321	SCV004165052	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	MECP2: BP4, BS2
RettBASE	RCV000169943	SCV000187900	uncertain significance	Rett syndrome	2007-11-15	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004544307	SCV004761082	likely benign	MECP2-related disorder	2022-06-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).