ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.320G>A (p.Arg107His)

dbSNP: rs1569084106
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV002264759 SCV002546479 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2022-07-07 reviewed by expert panel curation NM_001754.5(RUNX1):c.320G>A (p.Arg107His) is a missense variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant affects one of the hotspot residues established by the MM-VCEP for RUNX1 (R107) (PM1). This missense variant has a REVEL score >0.88 (0.953) (PP3). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 27112265). In summary, this variant meets the criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM1, PM2_supporting, PP1, PP3, PS4_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002549217 SCV003443837 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-01-26 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with familial platelet disorder with associated myeloid malignancy (PMID: 27112265). It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 107 of the RUNX1 protein (p.Arg107His). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 812740). 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 C0"). 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.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003541 SCV001161869 likely pathogenic Thrombocytopenia no assertion criteria provided research
Nadeem Sheikh Lab, University of the Punjab RCV002279704 SCV002564648 pathogenic Acute myeloid leukemia no assertion criteria provided clinical testing

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