The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought


In this report we described the case of a BRCA1/2 (BRCA) molecular testing performed on tumor sample in a High Grade Serous Ovarian Cancer (HGSOC) patient with two different Next Generation Tumor Sequencing (NGTS) pipelines. The two clinical reports leaded to apparently different BRCA status, providing important foods for thought. After NGTS, the gene sequencing information (i.e., reads) are aligned to the reference gene sequences obtained from public databases, in order to provide an uniform nomenclature for unambiguous variant designation. However, the criteria adopted for variant reporting in tissue test are not always univocal. Particularly, this is the case of rare and unclassified BRCA variants for which the molecular evaluation may be a relevant challenge. Here we described a BRCA1 unclassified variant that may be re-evaluated in the context of alternative BRCA1 transcripts due to its different biological effect. We underlined that an in-depth knowledge of BRCA testing is mandatory for its appropriate use.

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Fig. 1

Figure source:

Fig. 2

Source: Amplicon Suite software (SmartSeq, Novara, Italy)





Breast cancer


Ovarian cancer


Pathogenic variants


Poly ADP ribose polymerase inhibitor


Variants of unknown significance


High grade serous ovarian cancer


Tumor BRCA


Variant allele frequency


Minor allele frequency




BRCA1 full-length


Evidence-based network for the interpretation of germline mutant alleles


Nuclear localization signal


Germline BRCA


Single nucleotide variants


Copy number variations


Next generation sequencing


Multiplex amplification quantification


Multiplex ligation probe amplification


Microsatellite instability


Tumor mutational burden


American College of Medical Genetics


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We would like to thank Franziska M. Lohmeyer for critically reviewing this manuscript.


This research received no external funding.

Author information




EDP and AM conceived the project and wrote the paper; EDP and MDB performed the experiments and analysed the data; AU contributed to analyses and interpretation of data; AP, AF and GS contributed to patient selection and clinical evaluation. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Angelo Minucci.

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This study complied with the Ethical Principles for Medical Research Involving Human Subjects according to the World Medical Association Declaration of Helsinki and was certified by the Committee of the Applicable Institution of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

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Written informed consent was obtained from the patient included in this study.

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De Paolis, E., Pietragalla, A., De Bonis, M. et al. The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought. Mol Biol Rep 48, 2985–2992 (2021).

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  • BRCA1/2 genes
  • High grade serous ovarian cancer
  • C.788G > T
  • Tumor BRCA testing
  • Next generation sequencing