LAUSR

Sequence variant interpretation (SVI) is a formal process by which gene variants are classi fi ed as pathogenic (P), likely pathogenic (LP), variant of uncertain signi fi cance, likely benign (LB), or benign (B). The classi fi cations, based on the 28 criteria de fi ned by the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), 1 are intended to undergo gene-speci fi c modi fi cation facilitated by different Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEPs). The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) is charged with developing curation rules for genes in which variants confer risk for myeloid malignancies, starting with RUNX1 . 2,3 To re fl ect the continual updates from current literature and ClinVar submissions accu-rately, ClinGen advocates reevaluation of variant curation speci fi cations on a regular basis. In response to this recommendation coupled with additional re fi nement of ACMG/AMP criteria by the ClinGen SVI Working Group, the MM-VCEP has updated its RUNX1 curation rules to increase accuracy of curation in the fi elds of hematology, genetics, and pathology while optimizing clinical assessments of patients undergoing testing for inherited predisposition (Table 1; Figure 1A; supplemental case studies).