ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.415A>G (p.Asn139Asp)

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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 RCV004595676 SCV005088293 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-07-11 reviewed by expert panel curation NM_001754.5(RUNX1): c.415A>G (p.Asn139Asp) is a missense variant within the Runt Homology Domain (AA 89-204) (PM1_supporting). This variant has a REVEL score of 0.928 (PP3). Additionally, 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: PP3, PM1_supporting, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002918237 SCV003255550 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-06-16 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 C0"). 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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 139 of the RUNX1 protein (p.Asn139Asp).

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