ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1244dup (p.Pro415_Glu416insTer) (rs781843758)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493742 SCV000582571 pathogenic not provided 2015-09-03 criteria provided, single submitter clinical testing The c.1208dupC duplication in the MECP2 gene causes a frameshift starting with codon Glutamic acid 404 and changes this amino acid to a premature Stop codon, denoted p.E404X. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 83 amino acids of the MECP2 protein are lost. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this duplication has not been reported previously to our knowledge, we interpret it as a pathogenic variant.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197201 SCV001367838 pathogenic Epilepsy 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PM4. This variant was detected in hemizygous state.
Invitae RCV001231788 SCV001404320 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2019-11-23 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Glu404*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the MECP2 protein. This variant is present in population databases (rs781843758, ExAC 0.02%). This variant has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID:29655203). ClinVar contains an entry for this variant (Variation ID: 429893). This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region (p.Gln437Alafs*49) have been determined to be pathogenic (PMID: 11055898, 23696494, 10814718, 19914908, 16473305, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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