ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.334del (p.Leu112fs)

dbSNP: rs2057997486
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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 RCV004595571 SCV001244325 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-03-26 reviewed by expert panel curation The NM_001754.4:c.334del (p.Leu112CysfsTer10) variant is a frameshift variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). It has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; from internal laboratory data). 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, PS4_Supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001078216 SCV002238145 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-09-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu112Cysfs*10) 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. ClinVar contains an entry for this variant (Variation ID: 869209). 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).

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