Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000462167 | SCV000550161 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 267 of the RUNX1 protein (p.Met267Ile). This variant is present in population databases (rs757570529, gnomAD 0.007%). This missense change has been observed in individual(s) with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (PMID: 24523240, 27137476, 34166225). This variant is also known as p.Met240Ile. ClinVar contains an entry for this variant (Variation ID: 409818). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect RUNX1 function (PMID: 34166225). 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 | RCV003470457 | SCV004209843 | uncertain significance | Acute myeloid leukemia | 2023-09-26 | criteria provided, single submitter | clinical testing |