Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV002264726 | SCV002546436 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2022-07-05 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.1034C>G (p.Pro345Arg) variant is present in gnomAD v2.1.1 and v3.1.2 (MAF 0.0001153, 1/8676 in African/ African American subpopulation) and does not meet any of the population criteria defined by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1. REVEL score is not ≤0.50 (0.52). The variant has not been reported in patients with familial platelet disorder with a predisposition to hematologic malignancies in the literature, to the best of our knowledge. 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: N/A |
| Labcorp Genetics |
RCV000692644 | SCV000820477 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-09-19 | criteria provided, single submitter | clinical testing | 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: 571484). 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. 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 345 of the RUNX1 protein (p.Pro345Arg). |
| Baylor Genetics | RCV004569312 | SCV005055477 | uncertain significance | Acute myeloid leukemia | 2024-03-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004773100 | SCV005385833 | uncertain significance | not provided | 2024-02-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |