Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001389614 | SCV001591023 | pathogenic | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2020-06-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant is expected to result in the deletion of 212 amino acids of the RUNX1 protein (Asp269-Tyr480). While this is not anticipated to result in nonsense mediated decay, it is expected to result in the loss of the transcriptional activation domain (amino acid residues 318-398), DNA-binding inhibitory domain (residues 398-438), and VWRPY domain (residues 476-480) of the RUNX1 protein (PMID: 22689681, 23753029). Loss of these three domains from the mouse Runx1 protein has been shown to result in defects in thymocyte development (PMID: 15749889, 14504086). A similar gross deletion has not been reported in the literature in individuals with RUNX1-related disease. This variant is a gross deletion of the genomic region encompassing exons 8-9 of the RUNX1 gene. The 5' boundary is likely confined to intron 7. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. |