Submissions for variant NM_001110792.2(MECP2):c.1224C>T (p.Ser408=)

gnomAD frequency: 0.00019  dbSNP: rs781816931

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002472370	SCV002769730	benign	Rett syndrome	2022-12-09	reviewed by expert panel	curation	The allele frequency of the p.Ser396= variant in MECP2 (NM_004992.3) is 0.15% in European (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.Ser396= variant is observed in 1 unaffected individual (internal database) (BS2_supporting). In summary, the p.Ser396= variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1, BS2_supporting).
Genetic Services Laboratory, University of Chicago	RCV000193848	SCV000247939	uncertain significance	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088048	SCV000645657	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000659186	SCV000781003	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MECP2: BP4, BP7, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000193848	SCV001478801	benign	not specified	2021-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000659186	SCV001939584	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336513	SCV002634661	benign	Inborn genetic diseases	2017-08-25	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.
PreventionGenetics, part of Exact Sciences	RCV004541245	SCV004780263	likely benign	MECP2-related disorder	2022-08-29	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).