ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.952T>C (p.Ser318Pro)

dbSNP: rs545554349
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV002264777 SCV002546487 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2022-07-07 reviewed by expert panel curation The c.952T>C (p.Ser318Pro) missense variant has a REVEL score <0.50 (0.188) and SpliceAI does not predict (Δ scores ≤ 0.20) a significant impact on the canonical splice sites or the creation of putative cryptic splice sites (BP4). It has otherwise not been described in the literature. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001296221 SCV001485179 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-04-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 318 of the RUNX1 protein (p.Ser318Pro). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1000131). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RUNX1 protein function. 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.
Baylor Genetics RCV004570677 SCV005055483 uncertain significance Acute myeloid leukemia 2024-02-19 criteria provided, single submitter clinical testing

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