Table 2

 Missense substitutions in BRCA1 that have been observed with two or more known deleterious mutations

Missense substitutionObservationsHaplotype test
aa nament namehethomoWith B1*Diff B1†Indep‡Req’d?Resultcooc-LR
*Co-occurrence with known deleterious mutations in BRCA1; †co-occurrence with different known deleterious mutations in BRCA1; ‡confirmed independent occurrence of the unclassified and deleterious variants; ¶classified neutral/LCS in Goldgar et al7; §classification in Phelan et al26 meets the criteria for neutral/LCS of Goldgar et al7; **the deleterious mutation with which Ile1008 has been observed is 185delAG; all three co-occurrences are trans.
A. Known neutral/LCS missense substitutions
Q356R1186A>G4650(198)364111NANo–<1.0×10−10
D693N2196G>A5307(219)305131NANo–<1.0×10−10
K820E2577A>G95(4)86NANo–<1.0×10−10
R841W¶2640C>T117(0)44NANo–3.9×10−9
Y856H2685T>C31(1)22NANo–8.8×10−3
P871L2731C>T17 722(5399)1696440NANo–<1.0×10−10
E1038G3232A>G17 356(4234)1557407NANo–<1.0×10−10
S1040N3238G>A1611(22)11467NANo–<1.0×10−10
S1140G3537A>G97(1)43NANo–2.9×10−4
K1183R3667A>G17 440(4278)1562406NANo–<1.0×10−10
R1347G4158A>G433(2)2717NANo–<1.0×10−10
S1512I4654G>T278(1)1512NANo–<1.0×10−10
S1613G4956A>G17 454(4330)1565409NANo–<1.0×10−10
M1628T§5002T>C82(0)33NANo–1.6×10−4
M1652I5075G>A1049(8)7038NANo–<1.0×10−10
B. Unclassified missense substitutions
Y105C433A>G15(0)222Notrans1.1×10−5
Y179C655A>G40(1)331Yestrans1.2×10−2
S186Y676C>A28(1)310Nocis2.9×100
L246V855T>G67(0)3232Notrans2.6×10−5
F486L1575T>C41(1)331Yestrans1.2×10−2
R496H1606G>A73(0)732Notrans9.2×10−5
R504H1630G>A11(0)510Nocis1.3×100
N550H1767A>C40(1)331Yestrans1.2×10−2
L668F2121C>T22(0)1610Nocis1.3×100
V772A2434T>C44(0)3432Notrans9.4×10−6
M1008V3141A>G12(0)764Notrans<1.0×10−10
M1008I**3143G>A103(1)311Yestrans (3)9.6×10−7
E1060A3298A>C2(0)210Nocis1.0×100
E1250K3867G>A14(0)222Notrans1.0×10−5
D1546N4755G>A22(0)222Nounclear5.6×10−3
L1564P4810T>C11(0)431Yestrans3.3×10−3
P1637L5029C>T54(0)4910Nocis1.2×100
D1733G5317A>G3(0)310Nocis1.0×100