Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004696227 | SCV005196435 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-08-12 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.1253T>G (p.Met418Arg) is a variant which does not meet any ACMG/AMP criteria. 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. |
| Labcorp Genetics |
RCV000456503 | SCV000550146 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2024-07-21 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 418 of the RUNX1 protein (p.Met418Arg). This variant is present in population databases (rs202068364, gnomAD 0.02%). 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: 409805). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
| Breakthrough Genomics, |
RCV004696226 | SCV005195126 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Gene |
RCV004696226 | SCV005442937 | uncertain significance | not provided | 2024-06-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual suspected to have an inherited bleeding disorder (PMID: 28748566); This variant is associated with the following publications: (PMID: 28748566) |