ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1250C>G (p.Ser417Cys)

dbSNP: rs2145874727
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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 RCV002029177 SCV005367739 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-09-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.1250C>G (p.Ser417Cys) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has a REVEL score of 0.391, which is below the 0.50 threshold and a spliceAI score below the threshold of 0.2 (BP4). 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: BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002029177 SCV002305415 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-03-11 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 417 of the RUNX1 protein (p.Ser417Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RUNX1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

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