Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

Table 1 Revised multifactorial likelihood analysis of BRCA1 unclassified variants

BRCA1 variant	Previous multifactorial likelihood classification: odds for causality^a	Evolutionary conservation to Tetraodon and in BRCT domain	Sequence alignment prior probability^b	Myriad frequency (in trans with deleterious mutation)	LR from co-occurrence with a deleterious mutation	Segregation analysis: Bayes factor	Tumour histology (number analysed)	Grade	ER	CK 5/6	CK14	LR pathology	Multifactorial likelihood odds: co-occurrence, segregation, and pathology	Posterior probability of a variant being deleterious
BRCA1 5215 G>A (R1699Q)	141:1	Invariant, to Tetraodon, inside BRCT	0.73	33 (0)	3.010	1.043	Not BRCA1-like (1)	1	Pos	Neg	Neg	0.14	0.440	0.543
BRCA1 5242 C>T (A1708V)	41:1	Invariant, to Tetraodon, inside BRCT	0.73	6 (0)	1.220	0.227	BRCA1-like (1)	3	Neg	NA	NA	2.95	0.817	0.668
BRCA1 5242 C>A (A1708E)	262:1	Invariant, to Tetraodon, inside BRCT	0.73	76 (0)	12.700	4.470	BRCA1-like (1)	3	Neg	Pos	Pos (focal)	27.38	1554.024	0.999
BRCA1 5331 G>A (G1738R)	5871:1	Invariant, to Tetraodon, inside BRCT	0.73	8 (0)	1.300	20.250	BRCA1-like (1)	3	Neg	Neg	Pos (strong)	0.37	9.724	0.963
							Not BRCA1-like (1)	0	Pos	Neg	Neg

^aChenevix-Trench and colleagues [5] and Lovelock and colleagues [3]; ^bEaston and colleagues [19]. CK, cytokeratin; ER, estrogen receptor; LR, likelihood ratio; NA, not applicable; Neg, negative; Pos, positive.

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