ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.463G>C (p.Val155Leu)

gnomAD frequency: 0.00001  dbSNP: rs763464804
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004595636 SCV005088318 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-07-11 reviewed by expert panel curation NM_001754.5(RUNX1):c.463G>C (p.Val155Leu) is a missense variant which is located in the Runt Homology Domain, but does not occur at an established hotspot residue (PM1_supporting). Multiple lines of computational evidence supports a deleterious effect on the gene (REVEL: 0.904, phyloP100way: 7.568) (PP3). In summary, the clinical significance of this variant is uncertain due to insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PP3, PM1_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001947612 SCV002169475 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-07-17 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1401789). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is present in population databases (rs763464804, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 155 of the RUNX1 protein (p.Val155Leu). 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 expected to disrupt RUNX1 protein function. 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.

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