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Germline‐inactivating mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with a substantial increase in the risk of cancer.1 One of the possible outcomes of genetic testing for BRCA1 is the finding of an alteration in the BRCA1 coding region for which the risk of cancer has not been determined. These alterations have been termed unclassified variants (UCVs) or variants of uncertain significance. Most of these alterations are missense changes (Breast Cancer Information Core database, http://research.nhgri.nih.gov/bic/). We have developed a functional assay that aids in the determination of the association of cancer with BRCA1 UCVs.2,3 The assay measures the ability of a heterologous fusion of BRCA1 (or its mutants) to activate transcription.4,5 UCVs that activate transcription to levels comparable to the wild‐type protein represent neutral variants, whereas UCVs that abrogate or drastically reduce activity are associated with a predisposition to cancer.2,3 In a recent paper, we reported that BRCA1 variant M1628V presented markedly reduced activity in a transcriptional assay, which suggested that it represented a deleterious variant.2
During the course of additional experiments, we noticed that constructs containing the M1628V variant also included a deletion of nucleotides 5388–5582 (Entrez nucleotide accession U14680), leading to a truncated protein. Therefore, we generated new constructs for this variant using the primers and procedures described previously.2 We then repeated the transcription assays in yeast and mammalian cells (fig 11).). Contrary to what was reported,2 this variant displayed ~80% of the wild‐type activity, suggesting that it corresponds to a neutral variant. We regret this error and apologise for any confusion or inconvenience it may have caused.