Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004734489 | SCV005367798 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-09-30 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.1026C>G (p.Ile342Met) is a missense variant which has a REVEL score < 0.50 (0.016), and a SpliceAI score ≤ 0.20 (0.0) (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 |
RCV002299711 | SCV002589254 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2022-08-29 | 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 isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 342 of the RUNX1 protein (p.Ile342Met). |