ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1173dup (p.Val392fs) (rs1557135793)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000660654 SCV000782782 pathogenic Rett syndrome 2018-02-12 criteria provided, single submitter clinical testing
Invitae RCV000702922 SCV000831799 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2019-07-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Val380Argfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 107 amino acids of the MECP2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MECP2-related disease. Several truncations (p.Leu386Hisfs*5, and p.Pro389*) that lie downstream of this variant have been determined to be pathogenic (PMID: 19914908, 16473305). This suggests that deletion of this region of the MECP2 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001009240 SCV001169061 pathogenic not provided 2019-08-14 criteria provided, single submitter clinical testing The c.1137dupC variant in the MECP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1137dupC variant causes a frameshift starting with codon Valine 380, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Val380ArgfsX13. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1137dupC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1137dupC as a pathogenic variant.

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