Submissions for variant NM_001110792.2(MECP2):c.723G>T (p.Ser241=)

gnomAD frequency: 0.00001  dbSNP: rs782461567

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438000	SCV000535875	uncertain significance	not provided	2017-01-12	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MECP2 gene. The c.687 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.687 G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.687 G>T creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Additionally, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics	RCV002318492	SCV000851267	likely benign	Inborn genetic diseases	2016-09-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV001087926	SCV001091253	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2023-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000438000	SCV004165064	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	MECP2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003972661	SCV004787387	likely benign	MECP2-related condition	2023-05-22	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).