ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.40C>A (p.Pro14Thr)

dbSNP: rs1189256233
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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 RCV004734383 SCV005367725 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.40C>A (p.Pro14Thr) is a missense variant which has a REVEL score of < 0.50 (0.295) (BP4). 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, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002003125 SCV002275865 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-10-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This sequence change replaces proline with threonine at codon 14 of the RUNX1 protein (p.Pro14Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). 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. 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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