Evaluating the molecular diagnostic yield of joint genotyping-based approach for detecting rare germline pathogenic and putative loss-of-function variants.

ABSTRACT:

Purpose

Cohort-based germline variant characterization is the standard approach for pathogenic variant discovery in clinical and research samples. However, the impact of cohort size on the molecular diagnostic yield of joint genotyping is largely unknown.

Methods

Head-to-head comparison of the molecular diagnostic yield of joint genotyping in two cohorts of 239 cancer patients in the absence and then in the presence of 100 additional germline exomes.

Results

In 239 testicular cancer patients, 4 (7.4%, 95% confidence interval [CI]: 2.1-17.9) of 54 pathogenic variants in the cancer predisposition and American College of Medical Genetics and Genomics (ACMG) genes were missed by one or both computational runs of joint genotyping. Similarly, 8 (12.1%, 95% CI: 5.4-22.5) of

SUBMITTER: Camp SY 

PROVIDER: S-EPMC8720416 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature