ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.408T>A (p.Asn136Lys)

dbSNP: rs1569079130
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004735758 SCV005367758 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-09-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.408T>A (p.Asn136Lys) is a missense variant which has a REVEL score ≥ 0.88 (0.883) (PP3). This variant affects a residue within the Runt Homology domain (AA 89-204) but does not affect an established hotspot residue (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). 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: PP3, PM1_Supporting, PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000705057 SCV000834037 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2018-04-27 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change impairs the normal function of RUNX1 protein (PMID: 25840971). This variant has been observed in an individual affected with chronic myelomonocytic leukemia (PMID: 25840971). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 136 of the RUNX1 protein (p.Asn136Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine.

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