ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.1330G>A (p.Ala444Thr) (rs61753975)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659843 SCV000781716 likely benign Rett syndrome 2016-11-01 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224116 SCV000281659 benign not provided 2015-12-23 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000224116 SCV000804264 benign not provided 2015-04-03 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081198 SCV000113106 benign not specified 2013-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000081198 SCV000170235 benign not specified 2013-10-03 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 RCV000081198 SCV000193630 benign not specified 2013-02-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000081198 SCV000919616 benign not specified 2018-03-27 criteria provided, single submitter clinical testing Variant summary: MECP2 c.1330G>A (p.Ala444Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00098 in 200146 control chromosomes in the gnomAD database, including 55 hemizygotes. The observed variant frequency is approximately 118.11 fold above 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 benign. To our knowledge, no experimental evidence demonstrating the impact on protein function of c.1330G>A have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000556291 SCV000645660 benign Severe neonatal-onset encephalopathy with microcephaly 2017-08-31 criteria provided, single submitter clinical testing
RettBASE RCV000081198 SCV000187976 benign not specified 2010-05-14 no assertion criteria provided curation

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