Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001037580 | SCV004176264 | likely pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-12-09 | reviewed by expert panel | curation | PVS1_strong: Frameshift (+1); c.780-1440 as per VCEP specifications PM2_supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). PM5_supporting: Nonsense/frameshift variants that is downstream of c.98 (in transcript NM_001754.4). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting |
Invitae | RCV001037580 | SCV001201003 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the RUNX1 gene (p.Arg346Profs*254). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 135 amino acid(s) of the RUNX1 protein and extend the protein by 118 additional amino acid residues. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 836448). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Sung Lab, |
RCV003234570 | SCV003932623 | pathogenic | Acute myeloid leukemia | 2023-06-08 | no assertion criteria provided | clinical testing |