Submissions for variant NM_001110792.2(MECP2):c.1318G>A (p.Gly440Ser)

gnomAD frequency: 0.00011  dbSNP: rs61753971

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	RCV002260597	SCV002540679	benign	Rett syndrome	2022-05-10	reviewed by expert panel	curation	The allele frequency of the p.Gly428Ser (NM_004992) variant in MECP2 is 0.014% in gnomAD, which is high enough to meet BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Gly428Ser variant is observed in at least 2 unaffected individuals (PMID: 11238684, PMID: 12161600) (BS2). In summary the p.Gly428Ser variant in MECP2 is classified as Benign for Rett Syndrome based on the ACMG/AMP criteria (BS1, BS2).
GeneDx	RCV001719695	SCV000513573	likely benign	not provided	2021-06-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28454995, 11238684, 12161600, 11896461, 30560934)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000012604	SCV001008271	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371770	SCV002689596	likely benign	Inborn genetic diseases	2019-09-12	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.
Centre for Population Genomics, CPG	RCV002260597	SCV004098742	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). The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2, PMID: 11238684).
OMIM	RCV000012604	SCV000032839	pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2002-08-01	no assertion criteria provided	literature only
RettBASE	RCV000132982	SCV000187966	benign	not specified	2002-10-04	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004540997	SCV004765532	likely benign	MECP2-related disorder	2022-10-26	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).