ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.968C>T (p.Thr323Met) (rs61751445)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000426076 SCV000052826 likely benign not specified 2018-05-30 criteria provided, single submitter clinical testing Variant summary: MECP2 c.932C>T (p.Thr311Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.9e-05 in 178987 control chromosomes including 2 hemizygotes (gnomAD). The observed variant frequency is approximately 4.7 fold of 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. The variant, c.932C>T, has been reported in the literature in one individual affected with Rett Syndrome (Kim_2006). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000426076 SCV000513565 likely benign not specified 2017-01-06 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.
Invitae RCV001089108 SCV000766874 likely benign Severe neonatal-onset encephalopathy with microcephaly 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712288 SCV000842741 uncertain significance not provided 2018-05-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000719524 SCV000850392 likely benign History of neurodevelopmental disorder 2018-07-25 criteria provided, single submitter clinical testing Other data supporting benign classification;Does not segregate with disease in family study (genes with incomplete penetrance);Does not segregate in family study
RettBASE RCV000133294 SCV000188303 uncertain significance Mental retardation, X-linked, syndromic 13 2012-09-27 no assertion criteria provided curation
RettBASE RCV000030168 SCV000222573 uncertain significance Rett syndrome 2012-09-27 no assertion criteria provided curation

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