Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003405424 | SCV004123161 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2023-08-10 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.1229C>T (p.Ser410Leu) is a missense variant. This variant has a REVEL score of 0.339 which meets the threshold for benign variants (<0.5) and the SpliceAI delta score is 0 which is below the threshold for risk of splicing defects (<0.2) (BP4_met). 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 | RCV001234625 | SCV001407280 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 410 of the RUNX1 protein (p.Ser410Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 961001). This missense change has been observed in individual(s) with acute lymphoblastic leukemia (PMID: 34166225). |
Baylor Genetics | RCV003469427 | SCV004209828 | uncertain significance | Acute myeloid leukemia | 2023-10-29 | criteria provided, single submitter | clinical testing |