Table 2 Functional characterization of hMLH1 variants in the in vivo yeast-based system
From: Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2genes in yeast
MLH1 alteration | Nucleotide Change | Mutation rate (95% CI) | Functional classification | Summary of other functional studies | Summary of clinical data |
|---|---|---|---|---|---|
Missense variant | |||||
A92P | 274G>CA | 2.07 × 10-6 (1.17 × 10-6 - 2.96 × 10-6) | non-pathogenic |  |  |
S93Gb | 277A>G | 6.22 × 10-6 (2.50 × 10-6 - 9.94 × 10-6) | probably non-pathogenic | non-pathogenic | probably pathogenic |
T117M | 350C>T | 2.76 × 10-5 (1.28 × 10-5 - 4.23 × 10-5) | pathogenic | pathogenic | pathogenic |
I219V | 655A>G | 6.50 × 10-6 (2.20 × 10-6 - 1.08 × 10-5) | probably non-pathogenic | non-pathogenic | non-pathogenic |
K618Rb | 1853A>G | 4.99 × 10-6 (3.26 × 10-6 - 6.72 × 10-6) | probably non-pathogenic |  | probably pathogenic |
K618Ta | 1853A>C | 3.97 × 10-6 (1.78 × 10-6 - 6.16 × 10-6) | non-pathogenic | inconclusive | non-pathogenic |
Y646C | 1937A>G | 3.54 × 10-5 (1.78 × 10-5 - 5.31 × 10-5) | pathogenic | non-pathogenic | pathogenic |
R659Q | 1976G>A | 1.77 × 10-5 (8.52 × 10-6 - 2.70 × 10-5) | pathogenic | non-pathogenic | pathogenic |
Frameshift mutation | |||||
|  | 1955 del 1 bp | 1.86 × 10-4 (1.30 × 10-4 - 2.43 × 10-4) | loss-of-function |  |  |