ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.443C>G (p.Thr148Ser)

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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 RCV005245531 SCV005894761 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-10-29 reviewed by expert panel curation NM_001754.5(RUNX1):c.443C>G (p.Thr148Ser) is a missense variant which has a REVEL score < 0.50 (0.466) and a SpliceAI score ≤ 0.20 (0.02) (BP4). This variant affects one of the residues within the Runt Homology Domain (AA 89-204) but not in an established hotspot residue (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM1_supporting, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002296659 SCV002597035 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-10-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 148 of the RUNX1 protein (p.Thr148Ser).

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