Publications by authors named "C Rosa Fortuno"
Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.
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- Breast cancer continues to be a major global health issue, with increasing VUS complicating diagnosis in Australia’s healthcare system.
- This study examined VUS data from 11 familial cancer centers, revealing that 4% of variants might be reclassified as pathogenic and 80% as benign.
- Surveys indicated that there are challenges in VUS management due to limited resources, suggesting the need for routine reviews to improve patient care and communication between laboratories and cancer centers.
Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy.
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- The ENIGMA research consortium focuses on determining the clinical significance of variants in hereditary breast and ovarian cancer genes, specifically BRCA1 and BRCA2, and evolved from an external expert panel to an internal Variant Curation Expert Panel (VCEP) to enhance alignment with FDA recognized classification processes.
- The VCEP reviewed existing classification criteria and utilized statistical methods to assess evidence strength, testing new specifications on variants and updating documentation for better user clarity.
- Analysis led to refined classifications for variants—resolving uncertainties and maintaining confidence in others—while revealing gaps in both ENIGMA's research and ACMG/AMP criteria, ultimately improving the classification process for BRCA1 and BRCA2 variants.
Article Synopsis
- * Analysis of data from over 55,000 breast cancer patients showed that co-observation of variants in BRCA1, BRCA2, and PALB2 with other breast cancer genes occurred less frequently than expected, suggesting a potential correlation with pathogenicity.
- * The findings indicate that identifying a variant of uncertain significance alongside a known pathogenic variant supports evidence against the variant's pathogenicity, which could improve variant classification in clinical settings and for other genetic conditions.