Table 1.

Definitions of clinical classifications for comparison across databases

	BIC	ClinVar	HGMD	LOVD	UMD
Pathogenic	“Clinically important—yes”	“Pathogenic” “Probably pathogenic”	DM DM? FTV	“+/?” “+?/?”	“5—Causal” “4—Likely causal”
Uncertain (VUS)	“Clinically important—unknown”	“Variant of unknown significance” “Risk factor”	N/A	“?/?”	“3—UV”
Benign	“Clinically important—no”	“No known pathogenicity” “Probably not pathogenic”	FP DP DFP	“−/?” “−?/?”	“1—Neutral” “2—Likely neutral” “Polymorphism”
Other classifications	None	“Not provided” “Conflicting data from submitters”	None	None	“−”

Classifications for HGMD are defined as follows: “DM” is a disease causing (pathological) mutation, “DM?” is a likely disease causing (likely pathological) mutation, “FTV” is a frameshift or truncating variant with no disease association reported yet, “FP” is a polymorphism affecting the structure, function or expression of a gene but with no disease association reported yet, “DP” is a disease associated polymorphism, “DFP” is a disease associated polymorphism with additional supporting functional evidence (Stenson et al. 2009). Classifications for LOVD are defined as follows: “+” is pathogenic, “+?” is probably pathogenic, “?” is effect unknown, “-” is no known pathogenicity, and “-?” is probably no pathogenicity. All classifications are listed in the format “Reported/Concluded”, although for all variants in this data set, the Concluded classification was “?” (Fokkema et al. 2011). A VUS classification in UMD is defined as “3—UV”, referring to “uncertain variant” (Beroud et al. 2000).