ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.385_395del (p.Leu129fs)

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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 RCV004700884 SCV005205697 likely pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-10 reviewed by expert panel curation NM_001754.5(RUNX1):c.385_395del (p.Leu129AspfsTer5) is a frameshift variant that occurs which terminates 5 amino acids downstream and is predicted to undergo NMD (As per modified RUNX1 PVS1 decision tree ) (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a frameshift variant that is downstream of c.98 (PM5_Supporting). 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: PVS1_strong, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002996576 SCV003313580 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu129Aspfs*5) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). For these reasons, this variant has been classified as Pathogenic. 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).

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