ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5522G>A (p.Ser1841Asn) (rs80357368)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236784 SCV000292708 uncertain significance not provided 2016-01-19 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5522G>A at the cDNA level, p.Ser1841Asn (S1841N) at the protein level, and results in the change of a Serine to an Asparagine (AGT>AAT). Using alternate nomenclature, this variant would be defined as BRCA1 5641G>A. One set of in vitro functional assays interrogating this variant's impact on protein stability, peptide binding and specificity, and transcriptional activity suggests a pathogenic effect (Lee 2010). However, in vivo assays have found uncertain results. Growth assays by Quaresima et al. (2006) revealed that cells expressing BRCA1 Ser1841Asn were capable of forming comparable numbers of cell colonies as wild-type, but the Ser1841Asn colonies were reported to be smaller in size. Likewise, this study also found that cells expressing BRCA1 Ser1841Asn demonstrated reduced, but not absent, p53 binding (Quaresima 2006). BRCA1 Ser1841Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Asparagine share similar properties, this is considered a conservative amino acid substitution. This variant occurs at a position that is conserved across species and is located in the BRCT 2 domain as well as a region known to interact with multiple proteins (Narod 2004, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider BRCA1 Ser1841Asn to be a variant of uncertain significance.
Color RCV000583863 SCV000688640 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112694 SCV000145566 uncertain significance Breast-ovarian cancer, familial 1 2000-06-12 no assertion criteria provided clinical testing

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