ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.436A>T (p.Asn146Tyr)

dbSNP: rs2057887317
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004719104 SCV005326380 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-18 reviewed by expert panel curation NM_001754.5(RUNX1):c.436A>T (p.Asn146Tyr) is a missense variant which has a REVEL score ≥ 0.88 (0.978) (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). 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 RCV001220670 SCV001392675 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2019-07-03 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with tyrosine at codon 146 of the RUNX1 protein (p.Asn146Tyr). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and tyrosine.

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.