ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.527C>A (p.Thr176Asn)

dbSNP: rs2146236580
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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 RCV004734397 SCV005367733 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.527C>A (p.Thr176Asn) is a missense variant which has a REVEL score ≥ 0.88 (0.94) (PP3). This variant affects a residue within the Runt Homology domain (AA 89-294) but does not impact a residue which has been established as a hotspot (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). 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: PP3, PM1_supporting, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV002023291 SCV002306948 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-08-15 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 threonine with asparagine at codon 176 of the RUNX1 protein (p.Thr176Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine.

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