ClinVar Miner

Submissions for variant NM_004456.5(EZH2):c.1063C>A (p.Pro355Thr)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV004776149 SCV005383507 uncertain significance not provided 2024-02-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005104993 SCV005751231 uncertain significance Weaver syndrome 2024-04-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 355 of the EZH2 protein (p.Pro355Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EZH2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EZH2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.