Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome.

ABSTRACT:

Purpose

Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data.

Methods

The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes' rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants.

Results

The ge

SUBMITTER: Drost M 

PROVIDER: S-EPMC7200593 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature