ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.833C>T (p.Pro278Leu)

dbSNP: rs759227406
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004695245 SCV005196573 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.833C>T (p.Pro278Leu) is a missense variant which has a REVEL score of 0.491, below the threshold (<0.50) for pathogenicity. The SpliceAI score is 0.1 (threshold <0.20) for acceptor loss, indicating a very low chance this variant impacts splicing (BP4). 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: BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001233521 SCV001406121 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-04-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 278 of the RUNX1 protein (p.Pro278Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 960066). 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%. 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 RCV004570584 SCV005055485 uncertain significance Acute myeloid leukemia 2024-01-28 criteria provided, single submitter clinical testing

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