Submissions for variant NM_001110792.2(MECP2):c.1241C>T (p.Pro414Leu)

dbSNP: rs61753014

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002260613	SCV002540695	benign	Rett syndrome	2022-05-11	reviewed by expert panel	curation	The allele frequency of the p.Pro402Leu variant in MECP2 (NM_004992) is 0.011% in European (Non-Finnish) sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro402Leu variant is observed in at least 4 unaffected individuals (PMID 12384770) (BS2). In summary the p.Pro402Leu variant in MECP2 is classified as Benign for Rett syndrome disorder based on the ACMG/AMP criteria (BS1, BS2).
GeneDx	RCV000169924	SCV000170234	benign	not specified	2013-05-29	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000169924	SCV000604150	benign	not specified	2016-12-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088771	SCV000645658	benign	Severe neonatal-onset encephalopathy with microcephaly	2025-01-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316388	SCV000849969	likely benign	Inborn genetic diseases	2018-04-12	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.
CeGaT Center for Human Genetics Tuebingen	RCV000526298	SCV001156228	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483250	SCV002796258	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	2022-01-19	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV002260613	SCV004808998	benign	Rett syndrome	2024-03-13	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	RCV000169924	SCV000187946	benign	not specified	2002-12-20	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004544269	SCV004769029	likely benign	MECP2-related disorder	2022-04-07	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).