ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.814C>T (p.Gln272Ter)

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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 RCV003448474 SCV004176278 pathogenic Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2023-12-09 reviewed by expert panel curation The NM_001754.4:c.814C>T (p.Gln272Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and is 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). The variant has been reported in ClinVar but has not been observed in a proband meeting at least one of the RUNX1-phenotypic criteria. Nonsense variants downstream of c.98 (PM5_supporting) In summary, this variant meets the criteria to be classified as Pathogenic with 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 RCV003047176 SCV003341833 pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-04-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects RUNX1 function (PMID: 25840971). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant is also known as c.733C>T (p.Gln245*). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln272*) 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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