ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.56G>A (p.Arg19Lys)

gnomAD frequency: 0.00004  dbSNP: rs759078185
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477106 SCV000550157 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2023-12-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 19 of the RUNX1 protein (p.Arg19Lys). This variant is present in population databases (rs759078185, 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: 409814). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Genetic Services Laboratory, University of Chicago RCV001821277 SCV002068068 uncertain significance not specified 2020-04-28 criteria provided, single submitter clinical testing DNA sequence analysis of the RUNX1 gene demonstrated a sequence change, c.56G>A, in exon 2 that results in an amino acid change, p.Arg19Lys. This sequence change does not appear to have been previously described in patients with RUNX1-related disorders and has been described in the gnomAD database with a low population frequency of 0.0032% (dbSNP rs759078185). The p.Arg19Lys change affects a poorly conserved amino acid residue located in a domain of the RUNX1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg19Lys substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg19Lys change remains unknown at this time.
GeneDx RCV003223640 SCV003919489 uncertain significance not provided 2023-04-18 criteria provided, single submitter clinical testing 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
Baylor Genetics RCV003470456 SCV004209851 uncertain significance Acute myeloid leukemia 2023-09-08 criteria provided, single submitter clinical testing

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