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 For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant has not been reported in the literature in individuals 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.Thr178Hisfs*36) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product.

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