ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.231G>T (p.Thr77=) (rs80356847)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112084 SCV000578112 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000571917 SCV000665869 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-02 criteria provided, single submitter clinical testing The c.231G>T variant (also known as p.T77T), located in coding exon 4, results from a G to T substitution at nucleotide position 231 of the BRCA1 gene. This nucleotide substitution does not change the amino acid at codon 77. However, this variant was reported to affect splicing and cause increased exon-skipping using minigene assays (Raponi M et al. Hum. Mutat., 2011 Apr;32:436-44). This variant was previously reported in the SNPDatabase as rs80356847, but was absent from population-based cohorts in the NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project databases. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This nucleotide position is poorly conserved in available vertebrate species. The BDGP in silico model predicts a slight weakening in the native splice acceptor site efficiency while the ESEfinder tool does not predict any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of c.231G>T remains unclear.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112084 SCV000144748 uncertain significance Breast-ovarian cancer, familial 1 2000-06-12 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000112084 SCV001238505 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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