ClinVar Miner

Submissions for variant NM_001024630.4(RUNX2):c.1369C>T (p.Pro457Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005157729 SCV005783483 uncertain significance not provided 2024-05-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 457 of the RUNX2 protein (p.Pro457Ser). This variant is present in population databases (rs746700872, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RUNX2-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 RUNX2 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005358233 SCV005914724 uncertain significance Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome 2023-02-27 criteria provided, single submitter research

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