ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1195_1246del (p.Pro399fs)

dbSNP: rs1557135251
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002508196 SCV002818070 likely pathogenic not provided 2023-08-09 criteria provided, single submitter clinical testing Previously reported as c.1230del52 in a female patient with a clinical diagnosis of Angelman syndrome (Watson et al., 2001); Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11283202)
Invitae RCV003638635 SCV004525319 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2023-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro387Serfs*5) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 100 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Angelman syndrome (PMID: 11283202). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Pro469Alafs*18) have been determined to be pathogenic (PMID: 32860008). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 189662). This variant is also known as 1230del52.
OMIM RCV000012605 SCV000032840 pathogenic Atypical Rett syndrome 2001-04-01 no assertion criteria provided literature only
RettBASE RCV000170146 SCV000222474 pathogenic Angelman syndrome 2002-04-10 no assertion criteria provided curation

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