ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1174_1199del (p.Val392fs)

dbSNP: rs267608382
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV001262717 SCV002540675 pathogenic Rett syndrome 2022-05-10 reviewed by expert panel curation The p.Val380fs variant in MECP2 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Val380fs variant has been observed in at least 2 individuals with neurodevelopmental phenotypes (GeneDx internal cases) (PS4_Supporting). The p.Val380fs variant in MECP2 is absent from gnomAD (PM2_Supporting). In summary the p.Val380fs variant in MECP2 is classified as Pathogenic for Rett Syndrome based on the ACMG/AMP criteria (PVS1, PS4_Supporting, PM2_Supporting).
GeneDx RCV000132871 SCV001168944 pathogenic not provided 2022-02-24 criteria provided, single submitter clinical testing 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 a significant frequency in large population cohorts (gnomAD); Identified in a female with mild intellectual disability/developmental delay in published literature (Jarvela et al., 2021); This variant is associated with the following publications: (PMID: 21982064, 19914908, 20151026, 17387578, 17089071, 11453972, 33710394)
Center for Statistical Genetics, Columbia University RCV001261387 SCV001438297 pathogenic Intellectual disability 2020-10-16 criteria provided, single submitter research
Institute of Human Genetics, University of Leipzig Medical Center RCV001262717 SCV001440688 likely benign Rett syndrome 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV001386238 SCV001586379 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2021-09-01 criteria provided, single submitter clinical testing
RettBASE RCV000132871 SCV000187851 not provided not provided no assertion provided not provided

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