Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004694016 | SCV005196558 | pathogenic | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-08-01 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.585del (p.Thr196GlnfsTer15) is a frameshift variant which is predicted to introduce a premature stop codon, resulting in nonsense-mediated mRNA decay and affecting all three isoforms (PVS1). This variant is downstream of c.98 (PM5_supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). It has not been reported in individuals meeting at least one of the RUNX1 phenotypic criteria. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting. |
Labcorp Genetics |
RCV001965204 | SCV002213103 | pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2021-08-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr196Glnfs*15) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). |