ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.11C>T (p.Ser4Phe)

dbSNP: rs786203152
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166336 SCV000217122 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing The p.S4F variant (also known as c.11C>T), located in coding exon 1 of the BRCA1 gene, results from a C to T substitution at nucleotide position 11. The serine at codon 4 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In one study, functional analysis of this variant using a cisplatin sensitivity assay were inconclusive as repeat experiments showed discordant results (Bouwman P, Cancer Discov 2013 Oct; 3(10):1142-55). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000662889 SCV000785803 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-12-05 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237754 SCV002009473 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001850341 SCV002191692 uncertain significance Hereditary breast ovarian cancer syndrome 2024-09-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 4 of the BRCA1 protein (p.Ser4Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 26283626). ClinVar contains an entry for this variant (Variation ID: 186697). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Brotman Baty Institute, University of Washington RCV000662889 SCV001242176 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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