Table 6

New and existing combinations of exponent scores potentially leading to overall CanVIG-UK variant classifications

2015 ACMG framework assignation of variant classExponent score of evidence elementsExponent sumCanVIG-UK assignation of variant class
Towards pathogenicity: 8 (very strong), 4 (strong), 2 (moderate), 1 (supporting); towards benignity: −4 (strong), −1 (supporting)
Pathogenic (ia)8+412Pathogenic (ia)
Pathogenic (ib)8+2+212Pathogenic (ib)
Pathogenic (ic)8+2+111Pathogenic (ic)
Pathogenic (id)8+1+110Pathogenic (id)
L/pathogenic (i)8+210Pathogenic (ie)
Pathogenic (iiia)4+2+2+210Pathogenic (iia)
Pathogenic (iiib)4+2+2+1+110Pathogenic (iib)
Pathogenic (iiic)4+2+1+1+1+110Pathogenic (iic)
Not included4+4+210Pathogenic (iiia)
Not included4+4+1+110Pathogenic (iiib)
Not included2+2+2+2+210Pathogenic (iv)
Not included2+2+2+2+1+110Pathogenic (v)
Not included2+2+2+1+1+1+110Pathogenic (vi)
Not included2+2+1+1+1+1+1+110Pathogenic (vii)
Not included2+1+1+1+1+1+1+1+110Pathogenic (viii)
Not included1+1+1+1+1+1+1+1+1+110Pathogenic (viii)
Pathogenic (ii)4+48L/pathogenic (v)
L/pathogenic (ii)4+26L/pathogenic (i)
L/pathogenic (iii)4+1+16L/pathogenic (ii)
L/pathogenic (iv)2+2+26L/pathogenic (iii)
L/pathogenic (v)2+2+1+16L/pathogenic (iv)
L/pathogenic (vi)2+1+1+1+16L/pathogenic (vi)
Not included8+19L/pathogenic (vii)
Not included88N/A: single evidence element
Not included1+1+1+1+1+16L/pathogenic (viii)
L/benign (i)(−1)+(−4)-5L/benign (i)
L/benign (ii)(−1)+(−1)-2L/benign (ii)
Not included(−1)-1N/A: single evidence element
Not included(−4)-4N/A: single evidence element
Benign (i)(−4)+(−4)-8Benign (i)
  • Classifications in dark grey are those present in the 2015 ACMG framework that are inconsistent with the Tavtigian Bayesian metastructure, and those in light grey are new combinations generated using the exponent scoring system.

  • ACGS, Association for Clinical Genomic Science; ACMG, American College of Medical Genetics; CanVIG-UK, Cancer Variant Interpretation Group UK; L, likely; N/A, not applicable.