Variability in gene-based knowledge impacts variant classification: an analysis of FBN1 missense variants in ClinVar.

ABSTRACT: Gene-specific knowledge can enhance genetic variant classification, but may not be routinely incorporated into clinical laboratory practice. For example, FBN1 variants associated with Marfan syndrome may be variably classified depending on knowledge of FBN1-specific critical regions. In order to assess variability in classification of FBN1 variants, 674 FBN1 missense variants from 18 ClinVar submitters were compared and reanalyzed using FBN1-specific criteria and ACMG/AMP 2015 guidelines for variant interpretation. Conflicting variant classifications occurred in 30.7% of the missense variants that had multiple submitters. There were 451 classifications of 361 critical residue missense variants, with 80.0% (361/451) classified as likely pathogenic or pathogenic [(L)P]. Non-cysteine critical

SUBMITTER: Baudhuin LM 

PROVIDER: S-EPMC6777626 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature