Submissions for variant NM_001754.5(RUNX1):c.250G>A (p.Asp84Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004775471	SCV005382744	uncertain significance	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-10-29	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.250G>A (p.Asp84Asn) is a missense variant which does not meet any ACMG/AMP criteria. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003631032	SCV004460028	uncertain significance	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2023-04-27	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RUNX1 protein function. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is present in population databases (rs779860067, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 84 of the RUNX1 protein (p.Asp84Asn).