ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.585del (p.Thr196fs)

dbSNP: rs2146235121
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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 RCV004694016 SCV005196558 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-01 reviewed by expert panel curation NM_001754.5(RUNX1):c.585del (p.Thr196GlnfsTer15) is a frameshift variant which is predicted to introduce a premature stop codon, resulting in nonsense-mediated mRNA decay and affecting all three isoforms (PVS1). 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). It has not been reported in individuals meeting at least one of the RUNX1 phenotypic criteria. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001965204 SCV002213103 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-08-28 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 variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr196Glnfs*15) 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).

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