ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.988T>G (p.Phe330Val)

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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 RCV004694215 SCV005196544 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-07-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.988T>G (p.Phe330Val) is a missense variant which is absent from gnomAD v2 and v3 (PM2_supporting). This variant has not been reported in the literature. The computational predictor REVEL gives a score of 0.474, which is below the threshold of 0.50, and the splice site predictor SpliceAI indicated that the variant has no impact on splicing, evidence that does not predict a damaging effect on RUNX1 function (BP4). In summary, this variant meets the criteria to be classified as a variant of uncertain significance (VUS) for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: PM2_supporting and BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV002303478 SCV002593964 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-08-18 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: "Deleterious"; PolyPhen-2: "Benign"; 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 phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 330 of the RUNX1 protein (p.Phe330Val).

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