ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.503G>T (p.Gly168Val)

dbSNP: rs2057884016
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001250568 SCV001425422 uncertain significance Acute myeloid leukemia 2020-04-23 criteria provided, single submitter clinical testing This RUNX1 variant is absent from a large population dataset and has not been reported in the literature, to our knowledge, although disease-associated missense variants have been reported in nearby residues. Three bioinformatic tools queried predict that this substitution would be probably damaging, and the glycine residue at this position is evolutionarily conserved across all species assessed. Due to lack of functional and segregation data, we consider the clinical significance of c.503G>T to be uncertain at this time.
Invitae RCV003514493 SCV004259829 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 168 of the RUNX1 protein (p.Gly168Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myelodysplastic syndromes (PMID: 25840971). This variant is also known as c.422G>T (p.Gly141Val). ClinVar contains an entry for this variant (Variation ID: 973890). 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. Experimental studies have shown that this missense change affects RUNX1 function (PMID: 25840971). 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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