Submissions for variant NM_001754.5(RUNX1):c.1114_1125dup (p.Gly372_Thr375dup)

dbSNP: rs2056456863

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004693559	SCV005196569	uncertain significance	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-08-01	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.1114_1125dup (p.Gly372_Thr375dup) is an in-frame duplication which does not affect any residues within the Runt Homology Domain (AA 89-204) (PM4 not applied). 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: None.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064822	SCV001229746	uncertain significance	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-12-01	criteria provided, single submitter	clinical testing	This variant, c.1114_1125dup, results in the insertion of 4 amino acid(s) to the RUNX1 protein (p.Gly372_Thr375dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with RUNX1-related conditions. 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.