ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.233T>C (p.Met78Thr)

dbSNP: rs2058001205
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004720061 SCV005326374 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-18 reviewed by expert panel curation NM_001754.5(RUNX1):c.233T>C (p.Met78Thr) is a missense variant and is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score ≥ 0.88 (0.915) (PP3). The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. 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: PM2_supporting, PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV001065607 SCV001230573 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-08-10 criteria provided, single submitter clinical testing 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: 859484). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RUNX1 protein function. 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. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 78 of the RUNX1 protein (p.Met78Thr). This variant is not present in population databases (gnomAD no frequency).

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