Table 2.

Classification of variants in BRCA1

BRCA1 unclassified variantOccurrence in 180 ABCFS controlsFrequency in Myriad database (with a deleterious mutation)Bayes factor (no. families)Co-occurrenceSequence conservationA-GVGDLOH (no. tumors)Histopathology (no. tumors)Odds of causality, genetic data (frequency with a deleterious mutation and segregation data)Odds of causality, sequence data (sequence conservation and A-GVGD)Odds of causality, pathology data (LOH and immunohistopathology)Odds of causality, without pathology dataCombined odds of causality (genetic, sequence, and pathology data)Model classification
544 C > A (P142H)015 (1)1.7 (2)0.00430.003Not valid0.0055, no LOH (2), loss of UV (1)0.0069, not BRCA1-like (2)0.00731.000<0.00010.0073<0.0001Neutral
1225 del3 (D369del)010 (1)0.0213 (1)0.00340.003Not valid0.0045, loss of UV (2)8.7025, not BRCA1-like (1)<0.00011.0000.0391<0.0001<0.0001Neutral
1605 C > T (R496C)052 (1)1.95 (1)0.02240.003Not valid1, NA1, NA0.043681.00010.04370.0437NA
2531 G > C (Q804H)018 (0)1.12 (2)2.2440.003Valid, EN0.001951, no LOH (5)0.0087082, not BRCA1-like (5)2.513280.003<0.00010.00754<0.0001Neutral
2640 C > T (R841W)1207 (8)0.59 (2)<0.00010.003Not valid0.2860, loss of UV (1)0.4190, not BRCA1-like (1)<0.00011.0000.1198<0.0001<0.0001Neutral
3582 G > C (D1155H)000.0025 (1)1.00000.003Valid, EN0.0670, loss of UV (1)0.1390, not BRCA1-like (1)0.00250.0030.0093<0.0001<0.0001Neutral
4719 G > A (V1534M)032 (1)0.0086 (1)4.02200.001Valid, EN0.2860, no LOH (1)0.13900.03460.0010.0397<0.0001<0.0001Neutral
5215 G > A (R1699Q)019 (0)1.04 (1)2.347058Valid, ED1.0000 (NA)1.0000 (NA)2.4409581.0000141.571141.5710NA
5242 C > T (A1708V)01 (0)0.227 (1)1.045758Valid, ED12.9500, BRCA1-like (1)0.2374582.9513.767740.61467NA
5331 G > A (G1738R)04 (0)20.25 (3)1.258Valid, ED27.7729, loss of WT (2)0.15, BRCA1-like (1), not BRCA1-like (1)24.30584.16591409.45871.468Pathogenic
  • Abbreviations: UV, unclassified variant; WT, wild type; NA, not applicable; EN, enriched neutral; ED, enriched deleterious.