Submissions for variant NM_001110792.2(MECP2):c.1173C>T (p.Pro391=)

gnomAD frequency: 0.00020  dbSNP: rs61752980

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081192	SCV000113100	benign	not specified	2013-03-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587649	SCV000698529	benign	not provided	2016-12-26	criteria provided, single submitter	clinical testing	Variant summary: The MECP2 c.1137C>T (p.Pro379Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 29/80063 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0005728 (25/43643). This frequency is about 69 times the estimated maximal expected allele frequency of a pathogenic MECP2 variant (0.0000083), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV000720865	SCV000851749	benign	History of neurodevelopmental disorder	2017-05-30	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae	RCV001087585	SCV001004157	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000587649	SCV001939582	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV003380411	SCV004098757	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). Synonymous or intronic variant outside donor and acceptor splice regions where splicing prediction algorithms do not support significant splicing alteration (spliceAI score <=0.1) (BP4, BP7).
CeGaT Center for Human Genetics Tuebingen	RCV000587649	SCV004165054	likely benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	MECP2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003915074	SCV004734278	likely benign	MECP2-related condition	2019-03-07	criteria provided, single submitter	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).
RettBASE	RCV000081192	SCV000187849	benign	not specified	2002-12-20	no assertion criteria provided	curation