Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002264697 | SCV002546393 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2022-07-08 | reviewed by expert panel | curation | The NM_001754.5(RUNX1):c.1184C>G (p.Pro395Arg) variant is reported at an MAF of 0.00007728 (0.008%, 2/25880 alleles) in the Latino/Admixed American subpopulation of the gnomAD v2.1.1 cohort, and does not meet the threshold for BA1 (≥0.0015) or BS1 (0.00015 - 0.0015). The variant is reported in a patient in PMID: 32554555, but the proband does not meet criteria for PS4 due to the lack of germ line confirmation. The variant has a REVEL score of 0.334, which does not meet threshold for PP3 (≥0.88) or BP4 (<0.50). 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: none. |
Gene |
RCV000423989 | SCV000535407 | uncertain significance | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | 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 |
Invitae | RCV000799291 | SCV000938946 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 395 of the RUNX1 protein (p.Pro395Arg). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 392183). 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. |
Baylor Genetics | RCV003470385 | SCV004209832 | uncertain significance | Acute myeloid leukemia | 2023-10-17 | criteria provided, single submitter | clinical testing |