Submissions for variant NM_001110792.2(MECP2):c.553C>G (p.Pro185Ala)

gnomAD frequency: 0.00002  dbSNP: rs61748427

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	RCV000133148	SCV002769699	likely benign	Rett syndrome	2022-10-11	reviewed by expert panel	curation	The p.Pro173Ala variant in MECP2 (NM_004992.3) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome; this individual was reported to have a second variant in MECP2 that was classified as Pathogenic (PMID 11241840). The p.Pro173Ala variant in MECP2 (NM_004992.3) is observed in at least 2 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Pro173Ala variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5). The p.Pro173Ala variant in MECP2 is present in 3 female and 2 male individual(s) in gnomAD (0.0024%) (not sufficient to meet BS1 criteria). In summary, the p.Pro173Ala variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).
CeGaT Center for Human Genetics Tuebingen	RCV000513430	SCV000609421	uncertain significance	not provided	2017-02-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000766084	SCV000897559	uncertain significance	Severe neonatal-onset encephalopathy with microcephaly; Syndromic X-linked intellectual disability Lubs type; X-linked intellectual disability-psychosis-macroorchidism syndrome; Rett syndrome; Autism, susceptibility to, X-linked 3	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000513430	SCV001764578	likely benign	not provided	2019-05-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11241840)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002055855	SCV002322795	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2023-12-25	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV000133148	SCV004808751	likely benign	Rett syndrome	2024-03-14	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 3.0, this variant is classified as likely benign. At least the following criteria are met: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2). Variant is found in an individual with an alternate molecular basis of disease (BP5).
RettBASE	RCV000133148	SCV000188140	uncertain significance	Rett syndrome	2002-09-05	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004532604	SCV004712468	likely benign	MECP2-related disorder	2022-02-23	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).