ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1069C>T (p.Pro357Ser)

gnomAD frequency: 0.00001  dbSNP: rs375989348
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV000639527 SCV005196500 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-07-17 reviewed by expert panel curation NM_001754.5(RUNX1):c.1069C>T (p.Pro357Ser) is a missense variant which has a REVEL score < 0.50 (0.27), and a SpliceAI score ≤ 0.20 (0.0) (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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000639527 SCV000761102 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-08-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 357 of the RUNX1 protein (p.Pro357Ser). This variant is present in population databases (rs375989348, 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: 532667). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RUNX1 protein function with a negative predictive value of 80%. 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.
GeneDx RCV003441988 SCV004168504 uncertain significance not provided 2023-04-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004957928 SCV005495320 uncertain significance Inborn genetic diseases 2024-11-22 criteria provided, single submitter clinical testing The p.P357S variant (also known as c.1069C>T), located in coding exon 8 of the RUNX1 gene, results from a C to T substitution at nucleotide position 1069. The proline at codon 357 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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