ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1003C>T (p.Gln335Ter)

dbSNP: rs1569002881
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV001197295 SCV001367945 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-06-24 reviewed by expert panel curation The 1003C>T (p.Gln335Ter) variant is a nonsense variant that is not expected to result in nonsense-mediated mRNA decay, but the predicted truncated/altered region (removes aa 335-480) is critical to protein function (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge; however one unpublished proband meeting at least one of the RUNX1 phenotype criteria is noted (PS4_Supporting; SCV000807750.1). This variant is a nonsense/frameshift variant that is downstream of c.98 (PM5_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_Strong, PM2_supporting, PS4_Supporting, PM5_supporting.
PreventionGenetics, part of Exact Sciences RCV000680379 SCV000807750 likely pathogenic not provided 2016-08-18 criteria provided, single submitter clinical testing
Genetic Service Laboratory, Queen Elizabeth Hospital RCV002472312 SCV002758750 likely pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-12-06 criteria provided, single submitter clinical testing The variant is a nonsense variant that is not expected to result in nonsense-mediated mRNA decay (c.914-c.1440), but the predicted truncated/altered region (removes aa 335-480) is critical to protein function (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). The variant has been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature (Myeloid Malignancy VCEP and ClinVar). (PS4_Moderate; SCV001367945.1, SCV000807750.1).

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