ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1184C>G (p.Pro395Arg)

dbSNP: rs868527382
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 RCV002264697 SCV002546393 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2022-07-08 reviewed by expert panel curation The NM_001754.5(RUNX1):c.1184C>G (p.Pro395Arg) variant is reported at an MAF of 0.00007728 (0.008%, 2/25880 alleles) in the Latino/Admixed American subpopulation of the gnomAD v2.1.1 cohort, and does not meet the threshold for BA1 (≥0.0015) or BS1 (0.00015 - 0.0015). The variant is reported in a patient in PMID: 32554555, but the proband does not meet criteria for PS4 due to the lack of germ line confirmation. The variant has a REVEL score of 0.334, which does not meet threshold for PP3 (≥0.88) or BP4 (<0.50). 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: none.
GeneDx RCV000423989 SCV000535407 uncertain significance not provided 2023-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000799291 SCV000938946 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 395 of the RUNX1 protein (p.Pro395Arg). This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 392183). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function. 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.
Baylor Genetics RCV003470385 SCV004209832 uncertain significance Acute myeloid leukemia 2023-10-17 criteria provided, single submitter clinical testing

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.