ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2180C>T (p.Pro727Leu) (rs80356912)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077509 SCV001161493 benign Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000167
Ambry Genetics RCV000215724 SCV000275645 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000350348 SCV000329125 uncertain significance not provided 2016-06-03 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2180C>T at the cDNA level, p.Pro727Leu (P727L) at the protein level, and results in the change of a Proline to a Leucine (CCA>CTA). Using alternate nomenclature, this variant would be defined as BRCA1 2299C>T. This variant has been observed in at least one individual with a personal and family history of pancreatic cancer (Ghiorzo 2012). BRCA1 Pro727Leu 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 Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Pro727Leu occurs at a position that is not conserved and is located in the DNA binding domain and a region known to interact with multiple other 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 Pro727Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000215724 SCV000912042 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000350348 SCV001133516 uncertain significance not provided 2018-11-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077509 SCV000109309 uncertain significance Breast-ovarian cancer, familial 1 2011-02-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077509 SCV000144320 uncertain significance Breast-ovarian cancer, familial 1 1997-11-14 no assertion criteria provided clinical testing

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