ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.593A>T (p.Asp198Val)

dbSNP: rs1569061786
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004702402 SCV001244324 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-28 reviewed by expert panel curation NM_001754.4:c.593A>T (p.Asp198Val) is a missense variant which affects a hotspot residue within the RHD (PM1). Two probands meeting RUNX1-phenotypic criteria were reported to have this variant (PMID: 27479822; Internal laboratory data) (PS4_moderate). This variant has a REVEL score of 0.959 > 0.75 (PP3). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). Additionally, this variant is a missense change at the same residue (p.D198) where a different missense change has been previously established as a likely pathogenic variant (ClinVar ID 561251, 2665098) based on MM-VCEP rules for RUNX1 (PM5_Supporting). 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: PM1, PS4_moderate, PP3, PM2_supporting, PM5_supporting.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852167 SCV000899823 likely pathogenic Thrombocytopenia 2019-02-01 criteria provided, single submitter research
Birmingham Platelet Group; University of Birmingham RCV001270576 SCV001450875 likely pathogenic Abnormal bleeding; Thrombocytopenia 2020-05-01 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004723162 SCV005336585 pathogenic RUNX1-related disorder 2024-07-02 no assertion criteria provided clinical testing The RUNX1 c.593A>T variant is predicted to result in the amino acid substitution p.Asp198Val. This variant has been reported in several individuals with inherited thrombocytopenia/platelet disorder (reported as p.Asp171Val in Johnson. 2016. PubMed ID: 27479822; Table 2, Almazni et al. 2020. PubMed ID: 32935436; Table S3, Downes et al. 2019. PubMed ID: 31064749; Brown et al. 2020. PubMed ID: 32208489). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.