Table 7.

Validation of semi-quantitative approach for TP53 variant bioinformatic prediction using Align-GVGD class (optimized pMSA) and BayesDel score, using an independent set of non-functional and functional variants

Category	Non-functional (n)	%	Functional (n)	%	Positive LR (95% CI)	LR consistent with proposed ACMG/AMP rule (Table 5)
Optimized Align-GVGD C65 + BayesDel ≥0.16	94	48.45	49	4.32	11.20 (8.22, 15.27)	Yes - Moderate evidence of pathogenicity (new rule):18.7≥ Odds Path >4.3
Optimized Align-GVGD C55-C25 + BayesDel ≥0.16	51	26.29	61	5.38	4.88 (3.48, 6.86)	Yes - Supporting evidence of pathogenicity (PP3): 4.3≥ Odds Path >2.08
Optimized Align-GVGD C15 + BayesDel ≥0.16	11	5.67	27	2.38	2.38 (1.20, 4.72)	No - Not consistent enough with initial results to justify PP3
Optimized Align-GVGD C15 + BayesDel <0.16	1	0.51	42	3.71	0.14 (0.02, 1)	Yes - Supporting evidence of benign impact (BP4): 0.23< Odds Path <0.48
Optimized Align-GVGD C0 + BayesDel <0.16	14	7.22	819	72.29	0.10 (0.06, 0.17)	Yes - Supporting evidence of benign impact (BP4): 0.23< Odds Path <0.48