ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.315C>A (p.His105Gln)

dbSNP: rs1601528621
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV000824708 SCV000965660 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-10 reviewed by expert panel curation The NM_001754.4:c.315C>A (p.His105Gln) variant affects one of the residues (AA 105-204) within the RHD which is not an established hotspot residue (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). Transactivation assays demonstrating altered transactivation (<20% of wt, and/or reduced to levels similar to well-established pathogenic variants such as R201Q or R166Q) and data from secondary assays demonstrate altered DNA binding and functional consequences in mouse model. (PS3; PMID: 22318203; PMID: 25840971). This missense variant has a REVEL score >0.75 (0.901) (PP3). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PS3, PM2_supporting, PP3, PM1_supporting.

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