ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1252C>T (p.Gln418Ter) (rs61753965)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000132967 SCV000190999 pathogenic not provided 2018-08-02 criteria provided, single submitter clinical testing The Q406X nonsense mutation in the MECP2 gene has been reported previously in two affected males with developmental delay, absence of language, severe intellectual disability, progressive spasticity, and seizures; however, the mutation was inherited from obligate carrier females who had normal to borderline intelligence and normal X-inactivation studies (Meloni et al., 2000). Q406X was also reported as a de novo mutation in a female with developmental delay, behavior problems, moderate intellectual disability, unsteady gait, and 100% skewed X-inactivation (Kleefstra et al., 2004), and in an individual with epilepsy who was non-ambulatory (Kim et al., 2012). The Q406X mutation is predicted to cause loss of normal protein function through protein truncation, as 81 amino acids are lost. The variant is found in INFANT-EPI panel(s).
Genomic Medicine Lab, University of California San Francisco RCV000169933 SCV001167569 pathogenic Rett syndrome 2018-01-18 criteria provided, single submitter clinical testing
Invitae RCV001057731 SCV001222239 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2019-12-12 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Gln406*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 81 amino acids of the MECP2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with MECP2-related conditions (PMID: 10986043, 14560307, 22476991). ClinVar contains an entry for this variant (Variation ID: 143441). 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 (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.
RettBASE RCV000169933 SCV000187951 pathogenic Rett syndrome 2012-09-27 no assertion criteria provided curation
RettBASE RCV000170106 SCV000222427 pathogenic Mental retardation, X-linked, syndromic 13 2012-09-27 no assertion criteria provided curation

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