ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.746del (p.Gly249fs) (rs61749743)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000012620 SCV000282495 pathogenic Rett syndrome 2016-01-18 criteria provided, single submitter clinical testing This frameshift variant alters amino acid position 237 leading to premature termination codon 10 amino acids downstream. Variant is absent from large and broad cohorts of the ExAC project while it has been reported in at least seven RTT patients. Functional studies have shown the variant to alter the expression levels of several proteins, however the clinical relevance of these altered expressions are uncertain. Reputable databases list variant as “Pathogenic”. Considering all evidence, the variant was classified as Deleterious Variant.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506656 SCV000604151 pathogenic not specified 2017-03-24 criteria provided, single submitter clinical testing
Invitae RCV001045878 SCV001209752 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2019-01-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MECP2 gene (p.Gly237Valfs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 250 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 Rett Syndrome (PMID: 10805343, 18842453, 19724012). This variant is also known as 706delG in the literature. ClinVar contains an entry for this variant (Variation ID: 11846). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region (p.Gly255*) have been determined to be pathogenic (PMID: 23270700, 1241840, 17089071, 10508514). 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.
OMIM RCV000012620 SCV000032855 pathogenic Rett syndrome 2009-09-01 no assertion criteria provided literature only
RettBASE RCV000012620 SCV000188205 pathogenic Rett syndrome 2011-11-01 no assertion criteria provided curation

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