ClinVar Miner

Submissions for variant NM_001754.4(RUNX1):c.1184C>G (p.Pro395Arg) (rs868527382)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000423989 SCV000535407 uncertain significance not provided 2017-01-13 criteria provided, single submitter clinical testing The P395R variant in the RUNX1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P395R variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P395R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P395R as a variant of uncertain significance.
Invitae RCV000799291 SCV000938946 uncertain significance Familial platelet disorder with associated myeloid malignancy 2019-05-21 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 395 of the RUNX1 protein (p.Pro395Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 392183). 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"). 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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