ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.5C>T (p.Ala2Val)

dbSNP: rs179363901
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics RCV000012619 SCV000223841 likely pathogenic Rett syndrome criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001851806 SCV002183775 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2021-08-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MECP2 function (PMID: 28973632). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 11845). This missense change has been observed in individual(s) with Rett syndrome (PMID: 19034540, 19365833, 23238081). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 2 of the MECP2 protein (p.Ala2Val). The MECP2 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001110792.1, and corresponds to NM_004992.3:c.-156C>T in the primary transcript.
Centre for Population Genomics, CPG RCV000012619 SCV004808869 likely pathogenic Rett syndrome 2024-02-18 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely pathogenic. At least the following criteria are met: This variant has been identified as a de novo occurrence in at least 2 individuals with Rett syndrome, without confirmation of paternity and maternity (PM6_Strong). PMID 19034540, 19365833, ClinVar; [VCV000011845.5] At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4). PMID: 19365833 This variant is absent from gnomAD (PM2_Supporting).
GeneDx RCV004760328 SCV005370062 pathogenic not provided 2024-04-02 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, including impaired methionine excision and increased proteasomal degradation rate (PMID: 28973632); In silico analysis supports that this missense variant does not alter protein structure/function; Reported using an alternate transcript of the gene; This variant is associated with the following publications: (PMID: 23238081, 19365833, 27929079, 19034540, 32472557, 33057194, 35982159, 28973632)
OMIM RCV000012619 SCV000032854 pathogenic Rett syndrome 2009-04-01 no assertion criteria provided literature only
RettBASE RCV000012619 SCV000222627 likely pathogenic Rett syndrome 2016-04-26 no assertion criteria provided research

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