ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1145C>G (p.Pro382Arg)

dbSNP: rs2145876238
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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 RCV004774515 SCV005382763 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-10-29 reviewed by expert panel curation NM_001754.5(RUNX1):c.1145C>G (p.Pro382Arg) is a missense variant which is absent from all population databases, including gnomAD v2.1.1 and gnomAD v3.1.2, both of which provide coverage of at least 20x for the RUNX1 gene at this genomic position (PM2_supporting). This missense variant has a REVEL score >0.88 (0.942) (PP3). To our knowledge, this variant has not been reported before, and there are no other pathogenic or likely pathogenic amino acid changes affecting the same residue. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV001920145 SCV002161489 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-08-12 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 replaces proline with arginine at codon 382 of the RUNX1 protein (p.Pro382Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.

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