Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002264715 | SCV002546480 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2022-07-07 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.35C>T (p.Ser12Leu) is a missense variant. It has a REVEL score <0.50 (0.305) and SpliceAI score of <0.20 (Donor Loss of 0.02 at -23 bp) (BP4). It has been reported in one proband meeting at least one of the RUNX1-phenotype criteria (PS4_Supporting; PMID: 34166225). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Panel for RUNX1: BP4, PS4_Supporting. |
Invitae | RCV000639521 | SCV000761096 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2024-01-31 | 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 12 of the RUNX1 protein (p.Ser12Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with acute lymphoblastic leukemia (PMID: 34166225). ClinVar contains an entry for this variant (Variation ID: 532661). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Sema4, |
RCV002257886 | SCV002535861 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003465399 | SCV004209875 | uncertain significance | Acute myeloid leukemia | 2023-04-11 | criteria provided, single submitter | clinical testing |