Table 1.
Classification of Parkin missense variants used in this study
| Databases | Parkin variant | Assignment based on clinical evidence using Sherloc | Functional group from this study | Assignment based on clinical and functional evidence using Sherloc | Assignment from PDmutDB | Assignment from MDSGene | |
|---|---|---|---|---|---|---|---|
| 1 | Disease and population | p.R42P | Pathogenic | 1 | Pathogenic | Pathogenic | Definitely pathogenic |
| 2 | Disease and population | p.V56E | Pathogenic | 1 | Pathogenic | Pathogenic | Probably pathogenic |
| 3 | Disease and population | p.K211N | Pathogenic | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 4 | Disease and population | p.C212Y | Pathogenic | 1 | Pathogenic | Pathogenic | Definitely pathogenic |
| 5 | Disease and population | p.C238W | Pathogenic | 1 | Pathogenic | Pathogenic nature unclear | Probably pathogenic |
| 6 | Disease | p.C253Y | Pathogenic | 1 | Pathogenic | Pathogenic nature unclear | Definitely pathogenic |
| 7 | Disease and population | p.G284R | Pathogenic | 2 | Pathogenic | Pathogenic nature unclear | Probably pathogenic |
| 8 | Disease and population | p.T415N | Pathogenic | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 9 | Disease | p.C431F | Pathogenic | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 10 | Disease and population | p.C441R | Pathogenic | 1 | Pathogenic | Pathogenic nature unclear | Definitely pathogenic |
| 11 | Disease | p.T240R | Likely pathogenic | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 12 | Disease and population | p.R275W | Likely pathogenic | 1 | Pathogenic | Pathogenic nature unclear | Definitely pathogenic |
| 13 | Disease and population | p.G430D | Likely pathogenic | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 14 | Disease and population | p.A46T | Likely benign | 3 | Likely benign | Pathogenic nature unclear | Not mentioned |
| 15 | Disease and population | p.P153R | Likely benign | 4 | Benign | Pathogenic nature unclear | Not mentioned |
| 16 | Disease and population | p.M192L | Likely benign | 4 | Benign | Pathogenic | Not mentioned |
| 17 | Disease and population | p.R402C | Likely benign | 4 | Benign | Pathogenic nature unclear | Not mentioned |
| 18 | Disease and population | p.Q34R | Benign | 3 | Benign | Pathogenic nature unclear | Not mentioned |
| 19 | Disease and population | p.A82E | Benign | 4 | Benign | Pathogenic nature unclear | Not mentioned |
| 20 | Disease and population | p.S167N | Benign | 4 | Benign | Not pathogenic | Not mentioned |
| 21 | Disease and population | p.R334C | Benign | 5 | Benign | Pathogenic | Not mentioned |
| 22 | Disease and population | p.V380L | Benign | 4 | Benign | Not pathogenic | Not mentioned |
| 23 | Disease and population | p.D394N | Benign | 4 | Benign | Not pathogenic | Not mentioned |
| 24 | Disease and population | p.D18N | Uncertain significance | 4 | Likely benign | Pathogenic nature unclear | Not mentioned |
| 25 | Disease and population | p.R33Q | Uncertain significance | 4 | Likely benign | Pathogenic | Probably pathogenic |
| 26 | Disease and population | p.P37L | Uncertain significance | 5 | Likely benign | Pathogenic nature unclear | Possibly pathogenic |
| 27 | Disease and population | p.R42C | Uncertain significance | 4 | Likely benign | Pathogenic | Not mentioned |
| 28 | Disease and population | p.R42H | Uncertain significance | 4 | Likely benign | Pathogenic | Not mentioned |
| 29 | Disease | p.W54R | Uncertain significance | 3 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 30 | Disease and population | p.R104W | Uncertain significance | 3 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 31 | Disease | p.K161N | Uncertain significance | 2 | Pathogenic | Pathogenic | Definitely pathogenic |
| 32 | Disease | p.M192V | Uncertain significance | 4 | Uncertain significance | Pathogenic | Probably pathogenic |
| 33 | Population | p.V224A | Uncertain significance | 5 | Likely benign | Not mentioned | Not mentioned |
| 34 | Disease and population | p.R234Q | Uncertain significance | 5 | Likely benign | Pathogenic | Possibly pathogenic |
| 35 | Disease and population | p.T240M | Uncertain significance | 2 | Pathogenic | Pathogenic | Probably pathogenic |
| 36 | Population | p.V248I | Uncertain significance | 4 | Likely benign | Not mentioned | Not mentioned |
| 37 | Disease | p.C253F | Uncertain significance | 1 | Pathogenic | Pathogenic nature unclear | Probably pathogenic |
| 38 | Disease and population | p.R256C | Uncertain significance | 5 | Likely benign | Pathogenic nature unclear | Probably pathogenic |
| 39 | Disease and population | p.D280N | Uncertain significance | 4 | Likely benign | Pathogenic | Not mentioned |
| 40 | Disease | p.C289G | Uncertain significance | 1 | Pathogenic | Pathogenic | Definitely pathogenic |
| 41 | Disease and population | p.E310R | Uncertain significance | 4 | Likely benign | Pathogenic nature unclear | Probably pathogenic |
| 42 | Disease | p.G328E | Uncertain significance | 4 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 43 | Disease and population | p.R334H | Uncertain significance | 4 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 44 | Disease | p.T351P | Uncertain significance | 4 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 45 | Disease and population | p.G359D | Uncertain significance | 3 | Uncertain significance | Pathogenic | Not mentioned |
| 46 | Disease and population | p.R366W | Uncertain significance | 4 | Likely benign | Pathogenic | Not mentioned |
| 47 | Disease and population | p.R396G | Uncertain significance | 4 | Uncertain significance | Pathogenic nature unclear | Not mentioned |
| 48 | Disease | p.C418R | Uncertain significance | 1 | Pathogenic | Pathogenic nature unclear | Probably pathogenic |
| 49 | Disease and population | p.P437L | Uncertain significance | 2 | Pathogenic | Pathogenic nature unclear | Definitely pathogenic |
| 50 | Disease and population | p.E444Q | Uncertain significance | 4 | Uncertain significance | Pathogenic | Not mentioned |
| 51 | Disease and population | p.M458L | Uncertain significance | 5 | Likely benign | Pathogenic nature unclear | Not mentioned |