ClinVar Miner

Submissions for variant NM_001754.4(RUNX1):c.316T>A (p.Trp106Arg) (rs1555899735)

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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 RCV000824706 SCV000965658 likely pathogenic Familial platelet disorder with associated myeloid malignancy 2019-07-26 reviewed by expert panel curation The NM_001754.4:c.316T>A (p.Trp106Arg) variant affects one of the residues (AA 105-204) within the RHD (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). 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 assay demonstrate altered DNA binding. (PS3; PMID: 25840971). This missense variant has a REVEL score >0.75 (0.976) (PP3). All patients reported in literature with this variant were not confirmed as germline variants (PMID: 21828118, PMID: 19282830, PMID: 25840971). 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, PP3, PM1_supporting.
Genetic Services Laboratory, University of Chicago RCV000502317 SCV000596881 uncertain significance not specified 2015-09-29 criteria provided, single submitter clinical testing

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