ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1196C>T (p.Pro399Leu)

gnomAD frequency: 0.00010  dbSNP: rs63390262
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV001800445 SCV002047342 benign Rett syndrome 2021-12-13 reviewed by expert panel curation The allele frequency of the p.Pro387Leu (NM_004992.3) variant in MECP2 is 0.026% in South Asian sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro387Leu variant is observed in at least 2 unaffected individuals (PMID 12161600, GeneDx internal database) (BS2). In summary, the p.Pro387Leu variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224689 SCV000280687 likely benign not provided 2015-05-08 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000608016 SCV000698534 likely benign not specified 2017-11-22 criteria provided, single submitter clinical testing Variant summary: The MECP2 c.1160C>T (p.Pro387Leu) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 17/186675 control chromosomes (gnomAD) at a frequency of 0.0000911, which is approximately 11 times the estimated maximal expected allele frequency of a pathogenic MECP2 variant (0.0000083), suggesting this variant is likely a benign polymorphism. The variant of interest has been reported via a publication in a homozygous female suspected to have Rett syndrome (Bhanushali_2016), however, her father also carried the variant and was stated to be mentally normal. In addition, one clinical diagnostic laboratory classified this variant as likely benign. Taken together, this variant is classified as likely benign.
GeneDx RCV000224689 SCV000728726 likely benign not provided 2021-04-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 11309367, 16708070, 26755454, 28447035, 29206688)
Invitae RCV001087050 SCV000766872 benign Severe neonatal-onset encephalopathy with microcephaly 2021-08-27 criteria provided, single submitter clinical testing
RettBASE RCV000132908 SCV000187889 uncertain significance X-linked intellectual disability-psychosis-macroorchidism syndrome 2002-04-10 no assertion criteria provided curation

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