Submissions for variant NM_001110792.2(MECP2):c.1071A>G (p.Lys357=)

gnomAD frequency: 0.00157  dbSNP: rs61752362

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000146347	SCV000170228	benign	not specified	2013-06-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000146347	SCV000193620	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000146347	SCV000342394	benign	not specified	2016-06-07	criteria provided, single submitter	clinical testing
Invitae	RCV001084528	SCV000556757	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000716152	SCV000846988	benign	History of neurodevelopmental disorder	2016-07-01	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757450	SCV000885675	benign	not provided	2017-11-07	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV003380420	SCV004098867	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 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). Synonymous or intronic variant outside donor and acceptor splice regions where splicing prediction algorithms do not support significant splicing alteration (spliceAI score <=0.1) (BP4, BP7).
RettBASE	RCV000146347	SCV000187811	benign	not specified	2013-12-05	no assertion criteria provided	curation
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000146347	SCV001929400	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000146347	SCV001955141	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000146347	SCV001964875	benign	not specified		no assertion criteria provided	clinical testing