Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004595561 | SCV005088284 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-07-11 | reviewed by expert panel | curation | The NM_001754.5(RUNX1): c.-5_4del (p.Met1_Ala2del) represents an in-frame deletion and is not present in any population databases (gnomAD v2.1.1 and v3.1.2) with a minimum 20x coverage for RUNX1 (PM2_supporting). This variant affects the initiator methionine of the RUNX1 mRNA, located outside the hotspot residues or other residues (AA 89-204) within the RHD, as defined by the MM-VCEP for RUNX1. PM4 criteria apply, as the variant does not alter the predicted protein structure or function. Consequently, the subsequent in-frame methionine is positioned at codon 18. Notably, this variant has not been reported previously in individuals affected by RUNX1-related conditions. In summary, the clinical significance of this variant remains uncertain. ACMG/AMP criteria were applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting. |
Labcorp Genetics |
RCV001046228 | SCV001210122 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2019-03-28 | 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. This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the RUNX1 mRNA. The next in-frame methionine is located at codon 18. |