ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1265A>C (p.Glu422Ala)

gnomAD frequency: 0.00004  dbSNP: rs2056451758
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002480887 SCV002778593 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1; Acute myeloid leukemia 2022-02-08 criteria provided, single submitter clinical testing
Invitae RCV002537734 SCV003281511 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2021-09-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 422 of the RUNX1 protein (p.Glu422Ala). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RUNX1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Breakthrough Genomics, Breakthrough Genomics RCV004692385 SCV005195125 uncertain significance not provided criteria provided, single submitter not provided
Birmingham Platelet Group; University of Birmingham RCV001270553 SCV001450852 uncertain significance Abnormal bleeding; Thrombocytopenia 2020-05-01 no assertion criteria provided research

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