ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2518A>T (p.Ser840Cys) (rs377475866)

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 RCV000074573 SCV000108658 uncertain significance not specified 2017-05-31 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2518A>T at the cDNA level, p.Ser840Cys (S840C) at the protein level, and results in the change of a Serine to a Cysteine (AGT>TGT). Using alternate nomenclature, this variant would be defined as BRCA1 2637A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Ser840Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ser840Cys occurs at a position that is not conserved and is located in the DNA binding domain (Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Ser840Cys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000195551 SCV000254961 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-01 criteria provided, single submitter clinical testing
Counsyl RCV000077522 SCV000489620 uncertain significance Breast-ovarian cancer, familial 1 2016-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509761 SCV000608210 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing The p.S840C variant (also known as c.2518A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2518. The serine at codon 840 is replaced by cysteine, an amino acid with dissimilar properties. This variant has been observed in breast and/or ovarian cancer cohorts (Caux-Moncoutier V et al. Hum. Mutat., 2011 Mar;32:325-34; Martelotto LG et al. Genome Biol., 2014 Oct;15:484; Santonocito C et al, 2020 May;12). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV000509761 SCV000683040 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077522 SCV000109323 likely benign Breast-ovarian cancer, familial 1 2012-10-09 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.