Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003409633 | SCV004123158 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-11-13 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.899C>T (p.Thr300Met) is a missense variant. This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria. This missense variant has a REVEL score <0.50 (0.423)(BP4). There is no splicing effect predicted (SpliceAI=0). The variant has not been reported in patients with the RUNX1-defined phenotype. 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 |
Invitae | RCV000461356 | SCV000550152 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 300 of the RUNX1 protein (p.Thr300Met). This variant is present in population databases (rs758682659, gnomAD 0.005%). 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: 409809). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function with a negative predictive value of 80%. 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. |
Baylor Genetics | RCV003470455 | SCV004209850 | uncertain significance | Acute myeloid leukemia | 2024-01-26 | criteria provided, single submitter | clinical testing |