Table 1. Characteristics of the selected naturally occurring MLH1 variants.
Table 1—source data 1. MLH1 variants tested in this work.
elife-49138-table1-data1.xlsx (20KB, xlsx)
DOI: 10.7554/eLife.49138.004
| Variant* | Steady-state level (% of WT) | FoldX ΔΔG (kcal/mol) | ClinVar annotation¤ | DME# |
|---|---|---|---|---|
| E23D | 90.0 | 0.49 | VUS | 3 |
| I25T | 51.3 | 2.40 | VUS | 3 |
| A29S | 109.6 | 2.06 | (likely) pathogenic | 3 |
| M35R | 72.1 | 3.52 | (likely) pathogenic | 0 |
| I36S | 63.2 | 4.08 | VUS | NA |
| N38D | 63.5 | 1.61 | VUS | 2 |
| S44F | 9.8 | >15 | (likely) pathogenic | 0 |
| S44A | 103.2 | −1.35 | VUS | 3 |
| G54E | 15.3 | >15 | VUS | 1 |
| N64S | 96.3 | 2.16 | VUS | 1 |
| G67R | 35.0 | >15 | (likely) pathogenic | 0 |
| G67W | 14.5 | >15 | (likely) pathogenic | 0 |
| I68N | 62.5 | 2.22 | (likely) pathogenic | 0 |
| R69K | 104.9 | −0.18 | VUS | 3 |
| C77Y | 61.0 | 6.57 | (likely) pathogenic | 2 |
| F80V | 72.3 | 2.22 | (likely) pathogenic | 1 |
| T82I | 100.0 | 0.54 | (likely) pathogenic | 2 |
| R100P | 46.4 | −1.25 | (likely) pathogenic | 2 |
| E102D | 97.9 | 0.34 | (likely) pathogenic | 3 |
| A111V | 68.8 | 4.96 | (likely) pathogenic | 0 |
| T117M | 32.8 | 7.14 | (likely) pathogenic | 0 |
| T117R | 46.2 | 12.70 | (likely) pathogenic | 0 |
| A128P | 62.8 | 2.40 | (likely) pathogenic | 0 |
| D132H | 110.2 | −0.30 | (likely) benign | 3 |
| A160V | 107.3 | 0.38 | VUS | 3 |
| R182G | 87.9 | 2.60 | (likely) pathogenic | 3 |
| S193P | 100.7 | 2.73 | VUS | 0 |
| V213M | 103.9 | −0.81 | (likely) benign | 3 |
| R217C | 74.1 | 1.06 | VUS | 2 |
| I219V | 112.5 | 0.66 | (likely) benign | 3 |
| I219L | 121.9 | −0.05 | (likely) benign | 3 |
| R226L | 63.3 | 0.27 | (likely) pathogenic | 1 |
| G244V | 32.0 | >15 | VUS | 0 |
| G244D | 38.8 | >15 | (likely) pathogenic | 0 |
| H264R | 117.6 | −0.60 | VUS | 3 |
| R265C | 57.2 | 0.28 | (likely) pathogenic | 2 |
| R265H | 81.4 | 0.04 | VUS | 3 |
| E268G | 81.1 | 0.81 | (likely) benign | 2 |
| L272V | 80.0 | 1.95 | VUS | 3 |
| A281V | 82.5 | 0.87 | (likely) pathogenic | 3 |
| K286Q | 101.8 | 0.28 | VUS | 2 |
| S295G | 88.6 | 0.13 | (likely) pathogenic | 2 |
| H329P | 54.1 | 5.67 | (likely) pathogenic | 1 |
| V506A | 62.1 | 2.18 | VUS | 2 |
| Q542L | 110.2 | −1.56 | VUS | 3 |
| L549P | 63.7 | 5.17 | VUS | 0 |
| I565F | 65.9 | 9.64 | VUS | 0 |
| L574P | 34.4 | 11.97 | (likely) pathogenic | 0 |
| E578G | 103.2 | 0.45 | (likely) benign | 2 |
| L582V | 100.0 | 1.93 | VUS | 3 |
| L588P | 88.6 | 3.30 | VUS | 1 |
| K618A | 80.4 | 0.61 | VUS | 1 |
| K618T | 106.5 | 0.09 | (likely) benign | 0 |
| L622H | 61.1 | 4.97 | (likely) pathogenic | 0 |
| P640T | 61.1 | 3.78 | VUS | 0 |
| L653R | 66.1 | 3.22 | (likely) pathogenic | 0 |
| I655V | 89.1 | 1.03 | (likely) benign | 3 |
| I655T | 71.1 | 1.29 | VUS | 3 |
| R659P | 69.0 | 6.93 | (likely) pathogenic | 0 |
| R659Q | 84.9 | 2.41 | VUS | 2 |
| T662P | 72.7 | 5.23 | (likely) pathogenic | 0 |
| E663G | 72.0 | −0.23 | VUS | 3 |
| E663D | 97.2 | 0.66 | (likely) pathogenic | 2 |
| L676R | 36.8 | 5.12 | VUS | 0 |
| R687W | 115.4 | 1.12 | (likely) pathogenic | 0 |
| Q689R | 71.0 | −0.54 | (likely) benign | 3 |
| V716M | 100.1 | 1.41 | (likely) benign | 1 |
| H718Y | 73.7 | 0.16 | (likely) benign | 2 |
| K751R | 82.1 | −0.23 | (likely) benign | 3 |
*:boldfaced variants studied in detail; ¤: VUS: variant of unknown significance; #DME: dominant mutator effect See also source data (Table 1—source data 1).