Fig. 1. Workflow of the LDLR gene VUS variants re-evaluation. The workflow for the re-evaluation of the LDLR gene VUS variants involves three major analysis steps: 1) First, 94 different variants of LDLR gene were identified from 251 patients suspected familial hypercholesterolemia and requested LDLR sequence analysis between 2011 and 2021. A quality control phase (*) removed 28 of the identified variants. Those included variants outside the reportable range; exon variants and intron variants located within 25 bp of exon-intron boundaries. 2) Then, ACMG/AMP guideline was applied to classify the remaining 66 variants into pathogenic variant (PV), likely pathogenic variant (LPV), variant of uncertain significance (VUS), likely benign variant (LBV), and benign variant (BV). 3) Finally, VUS re-evaluation was performed following the ClinGen guideline.
Abbreviations: ACMG/AMP, American College of Medical Genetics/Association for Molecular Pathology; ClinGen, Clinical Genome Resource.

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