Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004773109 | SCV005382727 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-10-29 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.226C>T (p.Arg76Cys) is a missense variant which has a REVEL score ≥ 0.88 (0.911) (PP3). 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: PP3. |
Labcorp Genetics |
RCV000699282 | SCV000827986 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2018-02-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 76 of the RUNX1 protein (p.Arg76Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RUNX1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |