# Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer

## TL;DR

This study examines genetic test results in patients suspected of hereditary breast cancer, finding pathogenic variants and variants of uncertain significance.

## Contribution

The study provides insights into the frequency and classification of germline variants in a clinical multigene panel testing setting.

## Key findings

- 22.2% of patients had pathogenic variants, including BRCA2, BRCA1, MLH1, and RINT1.
- 41.7% of patients had variants of uncertain significance (VUSs) only.
- Some VUSs were later reclassified as likely pathogenic or benign based on updated databases.

## Abstract

To clarify the status of multigene panel testing for suspected hereditary breast cancer in our institute, and disclose the characteristics of the variants detected.

This was a retrospective study of individuals who underwent next-generation sequencing-based multigene panel testing at our institute to investigate hereditary genetic variants for suspected hereditary breast cancer.

We identified 36 women who underwent multigene panel testing: 8 (22.2%) had a pathogenic variant, with or without other variants of uncertain significance (VUSs); 15 (41.7%) had VUSs only; and 13 (36.1%) had negative genetic test results. Of the eight pathogenic variants, five were BRCA2 variants and one each were BRCA1, MLH1, and RINT1 variants. The VUSs included BRCA1 and BRCA2, as well as other breast cancer-associated genes, such as ATM, CDH1, CHEK2, and PALB2. Referring to the latest ClinVar database, one of the variants identified as a VUS at diagnosis was re-determined as likely pathogenic, and three of the variants identified as VUSs at diagnosis were re-determined as benign.

VUSs are frequently identified during testing and it is important to monitor these individuals because VUS evaluations can change over time.

The online version contains supplementary material available at 10.1007/s00595-025-02994-3.