ClinVar Miner

Submissions for variant NM_004456.5(EZH2):c.1876G>A (p.Val626Met)

dbSNP: rs587783625
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145972 SCV000193118 pathogenic Weaver syndrome 2014-04-09 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000145972 SCV002579297 pathogenic Weaver syndrome 2021-07-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000145972 SCV005835058 pathogenic Weaver syndrome 2024-10-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 626 of the EZH2 protein (p.Val626Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Weaver Syndrome (PMID: 29244146). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 158579). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt EZH2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects EZH2 function (PMID: 29244146). For these reasons, this variant has been classified as Pathogenic.
Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center RCV000145972 SCV000588200 pathogenic Weaver syndrome no assertion criteria provided research This is a de novo variant in EZH2. The patient's phenotype fits perfectly with Weaver Syndrome with tall stature and advanced bone age. This same variant is already in ClinVar in another patient with Weaver Syndrome.
GenomeConnect, ClinGen RCV001249312 SCV001423275 not provided EZH2-related disorder no assertion provided phenotyping only Variant interpretted as Pathogenic and reported on 12-04-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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