ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.848A>C (p.Gln283Pro)

dbSNP: rs1555885620
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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 RCV005052848 SCV005686392 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2025-01-15 reviewed by expert panel curation NM_001754.5(RUNX1):c.848A>C (p.Gln283Pro) is a missense variant in exon 8 of 9, not located in a hotspot or the RHD domain. It is not predicted to affect splicing or protein function ( REVEL score 0.355, SplicaAI score 0.01 ). The variant is absent from population databases. There is no available literature. In summary, the clinical significance of this variant remains uncertain due to insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001976690 SCV002258740 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-03-22 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 283 of the RUNX1 protein (p.Gln283Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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