ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1014_1033del (p.Leu339fs)

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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 RCV004701781 SCV005205722 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-28 reviewed by expert panel curation NM_001754.5(RUNX1):c.1014_1033del (p.Leu339ProfsTer?) is a frameshift variant which is not predicted to undergo NMD, and the truncated/altered region is critical for protein function (frameshift (+) c.780-c.1440 as per VCEP specifications) (PVS1_Strong). This variant is downstream of c.98 (PM5_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_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, PM5_supporting, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV003630725 SCV004503392 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-05-15 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 results in a frameshift in the RUNX1 gene (p.Leu339Profs*254). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 142 amino acid(s) of the RUNX1 protein and extend the protein by 112 additional amino acid residues.

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