ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1295G>C (p.Cys432Ser)

dbSNP: rs1279963921
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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 RCV004699603 SCV005205645 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-12 reviewed by expert panel curation NM_001754.5(RUNX1):c.1295G>C (p.Cys432Ser) is a missense variant which is present in only 1 individual in gnomAD 2.0 with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.467) and a Splice AI score <0.20 (BP4). 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: BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001964054 SCV002252485 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-11-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 432 of the RUNX1 protein (p.Cys432Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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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