Submissions for variant NM_001110792.2(MECP2):c.1191_1202del (p.Leu398_Pro401del)

dbSNP: rs782174572

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000170253	SCV002769733	benign	Rett syndrome	2022-12-09	reviewed by expert panel	curation	The allele frequency of the p.Leu386_Pro389del variant in MECP2 (NM_004992.3) is 0.019% in Latino/Admixed American sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Leu386_Pro389del variant is observed in 3 unaffected individuals (internal database) (BS2). The p.Leu386_Pro389del variant is found in 2 patients with an alternate molecular basis of disease (internal database) (BP5). The p.Leu386_Pro389del variant has been observed in 2 individuals with neurological disorders (PMID: 19914908, 23262346) (PS4 not met). In summary, the p.Leu386_Pro389del variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BS1, BS2, BP5).
GeneDx	RCV001552219	SCV001772870	likely benign	not provided	2020-09-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23262346, 19914908)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054017	SCV002390811	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2024-11-16	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV000170253	SCV004232229	benign	Rett syndrome	2024-01-15	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 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 3.0 (BA1).
RettBASE	RCV000170253	SCV000222585	uncertain significance	Rett syndrome	2013-06-12	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004734766	SCV005367200	likely benign	MECP2-related disorder	2023-08-10	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).