Submissions for variant NM_001754.5(RUNX1):c.968C>G (p.Thr323Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV004695277	SCV005196537	uncertain significance	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-07-25	reviewed by expert panel	curation	NM_001754.5(RUNX1):c.968C>G (p.Thr323Arg) is a missense variant. This variant is absent from both gnomAD v2.1 and gnomAD v3.1.2 (PM2_supporting). This variant has not been reported in any proband meeting at least one of the RUNX1-phenotypic criteria. This missense variant has a REVEL score <0.50 (0.055) (BP4). In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002979120	SCV003288405	uncertain significance	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2023-07-17	criteria provided, single submitter	clinical testing	An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 323 of the RUNX1 protein (p.Thr323Arg). This variant is not present in population databases (gnomAD no frequency). 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: 2076125). 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.