Lost in Interpretation: Evidence of Sequence Variant Database Errors.

ABSTRACT

Variant databases serve as a resource for clinical molecular genetics laboratories. There is evidence of widespread interpretive and syntactic errors within the entries of both small and large-scale variant databases used for germline clinical molecular genetic interpretation reports. The over-dependence on variant databases for variant annotation, classification and reporting may be a potential source of error to clinical molecular genetics laboratories. Recent evidence suggests 12-50% of clinical test reports are in significant conflict with clinical reports from other laboratories. A non-systematic literature review of evidence of discrepancies within frequently used genetic variant databases used for generating clinical genetic tests is provided. The implications of and recommendations for addressing variant annotation, classification and interpretive errors are discussed.