ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1757C>G (p.Pro586Arg) (rs1064795270)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481843 SCV000570918 uncertain significance not provided 2016-07-07 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1757C>G at the cDNA level, p.Pro586Arg (P586R) at the protein level, and results in the change of a Proline to an Arginine (CCT>CGT). Using alternate nomenclature, this variant would be defined as BRCA1 1876C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Pro586Arg 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 Proline and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro586Arg occurs at a position that is not conserved and is located in the DNA binding domain as well as the regions of interaction with RAD50 and STAT1 (Zhong 1999, Ouchi 2000, Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro586Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561830 SCV000668455 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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