ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.505dup (p.Arg169fs)

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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 RCV004595670 SCV005088344 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-03-26 reviewed by expert panel curation The NM_001754.5(RUNX1):c.505dup (p.Arg169LysfsTer?) is a frameshift variant in a gene in which loss-of-function is an established mechanism (Frameshift (+1); c.98-c.779 as per VCEP specifications) (PVS1). The variant affects the R169 amino acid residue within the RHD (PM1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This frameshift variant is downstream of c.98 in transcript NM_001754.4 (PM5_Supporting). In summary, this variant meets the criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM1, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002823682 SCV003199058 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-05-18 criteria provided, single submitter clinical testing 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 sequence change creates a premature translational stop signal (p.Arg169Lysfs*44) 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). This variant is not present in population databases (gnomAD no frequency).

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