ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.723C>G (p.His241Gln)

dbSNP: rs2057112854
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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 RCV004693863 SCV005196532 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-07-25 reviewed by expert panel curation NM_001754.5(RUNX1):c.723C>G (p.His241Gln) is a missense variant which is entirely absent from all population databases, including gnomAD v2.1.1 and v3.1.2, which provide coverage of at least 20x for the RUNX1 gene at this genomic position (PM2_supporting). Prediction scores cannot be considered, as this missense variant has a REVEL score of 0.633. Additionally, the affected amino acid residue, number 241, falls outside the RHD or residues 89-204. Furthermore, to our knowledge, there is no previous record of this variant, and no other pathogenic or likely pathogenic missense variants affecting the same amino acid residue or resulting in the same residue have been reported. In summary, the clinical significance of this variant is uncertain, and it meets ACMG/AMP criteria as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001922159 SCV002149210 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2022-01-27 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 241 of the RUNX1 protein (p.His241Gln). This variant is not present in population databases (gnomAD no frequency). 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: "Tolerated"; PolyPhen-2: "Probably 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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