ClinVar Miner

Submissions for variant NM_002397.5(MEF2C):c.565C>T (p.Arg189Ter)

dbSNP: rs587783747
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000146362 SCV000193646 pathogenic Intellectual disability, autosomal dominant 20 2014-02-04 criteria provided, single submitter clinical testing
Courtagen Diagnostics Laboratory,Courtagen Life Sciences RCV000146362 SCV000236514 pathogenic Intellectual disability, autosomal dominant 20 2014-07-09 criteria provided, single submitter clinical testing
GeneDx RCV000578993 SCV000681092 pathogenic not provided 2019-04-22 criteria provided, single submitter clinical testing Identified in a patient with global developmental delay in published literature (Wang et al., 2018); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30376817, 31512412)
Invitae RCV000146362 SCV001233588 pathogenic Intellectual disability, autosomal dominant 20 2021-09-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg189*) in the MEF2C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEF2C are known to be pathogenic (PMID: 20513142). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with severe intellectual disability, stereotypic movements and hypotonia (PMID: 30376817). ClinVar contains an entry for this variant (Variation ID: 158886). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000146362 SCV002555971 likely pathogenic Intellectual disability, autosomal dominant 20 2022-06-17 criteria provided, single submitter clinical testing Variant summary: MEF2C c.565C>T (p.Arg189X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.766C>T [p.Arg256Ter]; c.833del [p.Leu277_Leu278insTer]). The variant was absent in 249200 control chromosomes (gnomAD). c.565C>T has been reported in the literature in at least one individual affected with Rett-Like Intellectual Disability (Wang_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all three classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
PerkinElmer Genomics RCV000146362 SCV002017257 pathogenic Intellectual disability, autosomal dominant 20 2021-06-11 no assertion criteria provided clinical testing

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