Table 3.

Comparison of the number of correctly identified and misclassified FH individuals in a hypothetical sample of 10,000 children, between the historical data(13) and the current study.

	Predicted cases based on the frequency of 1 in 500	Historical data	ALSPAC data
			Sequenced data only	Extrapolated (if no further mutations found)	Extrapolated (adjusted for verification bias)	Extrapolated (adjusted for verification bias and NGS misclassification)
		DR = 85% FPR = 0.1%	DR = 83% FPR = 0.8%	DR = 83% FPR = 0.2%	DR = 63% FPR = 0.2%	DR = 66.7% FPR = 0.2%
		ID: M/C	ID: M/C	ID: M/C	ID: M/C	ID: M/C
Children (N = 10,000)	20	17: 10	17: 80	17: 20	13: 20	13: 20
Parents (N = 20,000)	20	16: 11	16: 81	16: 21	13: 20	13: 20
If initial biochemical screening was followed by NGS
Children (N = 10,000)	20	17: 0	17: 0	17: 0	13: 0	13: 0
Parents (N = 20,000)	20	17: 0	17: 0	17: 0	13: 0	13: 0

Under all scenarios, the interpolation of a NGS for samples from all children who screen positive on the basis of an LDL-C above the diagnostic threshold, would reduce the misclassification rate to 0%.

DR = detection rate; FPR = false positive rate; NGS = next generation sequencing; ID: M/C = ratio of identified to misclassified.