Classification of genetic variants in genes associated with Lynch syndrome using a clinical history weighting algorithm

Table 1 Classification thresholds utilized by the history weighting analysis tool

Classification call	Log history weighting score compared to pathogenic composite controls	Log history weighting score compared to benign composite controls
Pathogenic	<99th Percentile	<0.5 Percentile - 2.2/2.3/2.2 SD
Weak Pathogenic^a	≥99th Percentile and ≤ 99.5 Percentile + 0.7/0.9/1.0 SD	<0.5 Percentile - 2.2/2.3/2.2 SD
Not Callable	>99.5 Percentile + 0.7/0.9/1.0 SD	<0.5 Percentile - 2.2/2.3/2.2 SD
Weak Benign^a	>99.5 Percentile + 0.7/0.9/1.0 SD	≥0.5 Percentile - 2.2/2.3/2.2 SD
Weak Benign^a	>99.5 Percentile + 0.7/0.9/1.0 SD	≤1st Percentile
Benign	>99.5 Percentile + 0.7/0.9/1.0 SD	>1st Percentile
Indeterminate	All Other Variants

Gene-specific standard deviations (SD) are indicated for MLH1, MSH2 and MSH6, respectively
^aPathogenic and benign ECDF control curve thresholds must not overlap

ISSN: 2730-6844