ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.172C>G (p.Pro58Ala) (rs397508904)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481979 SCV000568436 uncertain significance not provided 2016-10-26 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.172C>G at the cDNA level, p.Pro58Ala (P58A) at the protein level, and results in the change of a Proline to an Alanine (CCT>GCT). Using alternate nomenclature, this variant has been previously published as BRCA1 291C>G. This variant was observed in individuals with a personal and/or family history of breast and/or ovarian cancer (Ang 2007, Seymour 2008). BRCA1 Pro58Ala 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 Alanine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Pro58Ala occurs at a position that is not conserved and is located in the RING finger domain ubiquitination site as well as BRD7 and BARD1 interaction regions (Borg 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro58Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000575682 SCV000668486 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Conflicting evidence

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