ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3650C>G (p.Ser1217Cys) (rs398122676)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159979 SCV000210151 uncertain significance not provided 2017-08-03 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3650C>G at the cDNA level, p.Ser1217Cys (S1217C) at the protein level, and results in the change of a Serine to a Cysteine (TCT>TGT). Using alternate nomenclature, this variant would be defined as BRCA1 3769C>G. This variant has been observed in at least four Korean breast and/or ovarian cancer patients, but also in 9/96 unaffected Korean controls in one study (Jang 2012, Park 2016, Shin 2016, Park 2017). BRCA1 Ser1217Cys was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ser1217Cys occurs at a position that is not conserved and is not located in a known functional domain. 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 Ser1217Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000077128 SCV000487959 uncertain significance Breast-ovarian cancer, familial 1 2015-12-13 criteria provided, single submitter clinical testing
Invitae RCV000697628 SCV000826249 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-03-28 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1217 of the BRCA1 protein (p.Ser1217Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs398122676, ExAC 0.02%). This variant has been reported in several individuals affected with breast and/or ovarian cancer (PMID: 22217648, 27383479, 27124784, 28111427), as well as in unaffected individuals (PMID: 22217648). ClinVar contains an entry for this variant (Variation ID: 91611). Based on a multifactorial likelihood algorithm using genetic and in silico data, this variant has been determined to have a low probability of being pathogenic (PMID: 27124784). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001020804 SCV001182334 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-20 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV001020804 SCV001340477 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077128 SCV000108925 uncertain significance Breast-ovarian cancer, familial 1 2011-08-31 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.