Submissions for variant NM_001110792.2(MECP2):c.191A>G (p.His64Arg)

dbSNP: rs61754433

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002472326	SCV002769692	benign	Rett syndrome	2022-10-11	reviewed by expert panel	curation	The allele frequency of the p.His52Arg variant in MECP2 (NM_004992.3) is 0.121% in the South Asian 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). In summary, the p.His52Arg variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001520931	SCV001730147	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001689675	SCV001915565	benign	not provided	2020-02-17	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV002472326	SCV004101592	benign	Rett syndrome	2023-10-12	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).
Ambry Genetics	RCV004639141	SCV005133820	likely benign	Inborn genetic diseases	2024-06-16	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.
RettBASE	RCV000133025	SCV000188012	uncertain significance	not specified	2006-02-03	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004734683	SCV005363453	likely benign	MECP2-related disorder	2024-05-31	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).