ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1036C>T (p.Arg346Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004695266 SCV005196574 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.1036C>T (p.Arg346Cys) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). ClinVar has one entry for this variant (Invitae, ClinVar ID 2062797), but the affected status is unknown. To our knowledge, this variant has not been reported in the literature in individuals affected with RUNX1-related conditions. 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: PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002958014 SCV003273062 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-03-26 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 346 of the RUNX1 protein (p.Arg346Cys).

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