ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.789C>T (p.Pro263=) (rs63582063)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000133227 SCV000193640 likely benign not specified 2015-04-10 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000133227 SCV000310762 likely benign not specified criteria provided, single submitter clinical testing
Invitae RCV001085738 SCV000645676 benign Severe neonatal-onset encephalopathy with microcephaly 2020-09-03 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712284 SCV000842735 benign not provided 2017-12-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000719501 SCV000850368 likely benign History of neurodevelopmental disorder 2016-02-08 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000133227 SCV001362254 benign not specified 2019-02-15 criteria provided, single submitter clinical testing Variant summary: The variant, MECP2 c.753C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00015 in 199952 control chromosomes (14 hemizygotes), predominantly at a frequency of 0.00051 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 61-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MECP2 causing Rett Syndrome phenotype (8.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant, c.753C>T has been reported in the literature in individuals affected with Rett Syndrome (Chae_2004, Petel-Galil_2006, Temudo_2009, Hadzsiev_2011). However, these reports do not provide unequivocal conclusions about association of the variant with Rett Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000712284 SCV001941763 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
RettBASE RCV000133227 SCV000188227 benign not specified 2011-11-01 no assertion criteria provided curation

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