ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.528_531dup (p.Thr178fs)

dbSNP: rs2146236515
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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 RCV003448408 SCV004176277 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation The NM_001754.5(RUNX1):c.528_531dup (p.Thr178fs) variant is a frameshift variant predicted to introduce a premature stop codon, resulting in nonsense-mediated mRNA decay (PVS1). Additionally, it is located in c.528_531, which is downstream of c.98 (in transcript NM_001754.4) (PM5_Supporting). This variant is completely absent from all population databases (gnomAD v2.1.1, v3.1.2, and v4.0.0) with at least 20x coverage for RUNX1 (PM2_supporting). . 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 RCV001387849 SCV001588569 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2020-03-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr178Hisfs*36) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RUNX1-related conditions. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). For these reasons, this variant has been classified as Pathogenic.

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