Submissions for variant NM_001110792.2(MECP2):c.1192dup (p.Leu398fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003008535	SCV003307964	pathogenic	Severe neonatal-onset encephalopathy with microcephaly	2022-02-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu386Profs*7) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 101 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Glu432Glyfs*4) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003126264	SCV003803871	likely pathogenic	Developmental disorder	2019-10-07	criteria provided, single submitter	clinical testing