ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.331A>C (p.Thr111Pro)

dbSNP: rs1555899722
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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 RCV004719156 SCV005326381 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-18 reviewed by expert panel curation NM_001754.5(RUNX1):c.331A>C (p.Thr111Pro) is a missense variant which has a REVEL score ≥ 0.88 (0.961) (PP3). This variant affects a codon within the Runt Homology domain (AA 89-204) but does not occur within an established hotspot residue (PM1_Supporting). 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: PP3, PM1_supporting.
Johns Hopkins Genomics, Johns Hopkins University RCV001376147 SCV001573159 uncertain significance Acute myeloid leukemia 2021-04-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003629184 SCV004483846 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-12-31 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 1065582). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 111 of the RUNX1 protein (p.Thr111Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions.

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