ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.301G>A (p.Val101Met)

dbSNP: rs2146409049
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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 RCV004774594 SCV005382702 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-10-29 reviewed by expert panel curation NM_001754.5(RUNX1):c.301G>A (p.Val101Met) is a missense variant which has a REVEL score ≥ 0.88 (0.899) (PP3). This variant affects one of the residues within the Runt Homology Domain (AA 89-204) but not in an established hotspot residue (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_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, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001986641 SCV002286289 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-11-04 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1493649). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 101 of the RUNX1 protein (p.Val101Met).

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