Submissions for variant NM_001110792.2(MECP2):c.1162C>T (p.Pro388Ser)

gnomAD frequency: 0.00108  dbSNP: rs61752387

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000659842	SCV002540681	benign	Rett syndrome	2022-04-28	reviewed by expert panel	curation	The allele frequency of the c.1126C>T, p.(Pro376Ser) variant in MECP2 (NM_004992.4) is 0.13% 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.(Pro376Ser) variant is observed in at least 2 unaffected individuals (PMID 10944854, PMID 14560307, RettBASE) (BS1). In summary, the p.(Pro376Ser) variant in MECP2 is classified as Benign based on the ACMG/AMP criteria applied (BA1, BS2).
Eurofins Ntd Llc (ga)	RCV000081191	SCV000113099	benign	not specified	2015-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000081191	SCV000170230	benign	not specified	2013-10-22	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	RCV000081191	SCV000193622	benign	not specified	2020-05-29	criteria provided, single submitter	clinical testing
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000081191	SCV000537193	benign	not specified	2015-07-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000458852	SCV000556737	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-31	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659842	SCV000781715	uncertain significance	Rett syndrome	2016-11-01	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000659842	SCV000803468	benign	Rett syndrome	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Benign, for Rett syndrome, in X-linked Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. BS4 => Lack of segregation in affected members of a family (PMID:12567420) (PMID:12161600). BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000081191	SCV001469967	benign	not specified	2020-03-18	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000081191	SCV001476541	benign	not specified	2020-03-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444549	SCV002753506	benign	Inborn genetic diseases	2017-06-12	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000659842	SCV004098774	benign	Rett syndrome	2023-07-06	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 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).
RettBASE	RCV000081191	SCV000187840	benign	not specified	2010-05-14	no assertion criteria provided	curation
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000081191	SCV001931736	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081191	SCV001955409	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081191	SCV001967511	benign	not specified		no assertion criteria provided	clinical testing