ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2065A>G (p.Ser689Gly) (rs876660188)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219139 SCV000277398 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-28 criteria provided, single submitter clinical testing
GeneDx RCV000400810 SCV000329123 uncertain significance not provided 2016-05-12 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2065A>G at the cDNA level, p.Ser689Gly (S689G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). Using alternate nomenclature, this variant would be defined as BRCA1 2184A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Ser689Gly 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 Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ser689Gly occurs at a position that is not conserved and is located in the DNA binding domain and a region known to interact with multiple proteins (Narod 2004, Paul 2014). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Ser689Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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