ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5429T>G (p.Val1810Gly)

dbSNP: rs80357451
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000112654 SCV001140466 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112654 SCV000145512 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 1997-11-14 no assertion criteria provided clinical testing
Brotman Baty Institute, University of Washington RCV000112654 SCV001238384 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355658 SCV001550602 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Val1810Gly variant was identified in 1 of 1978 proband chromosomes (frequency: 0.0005) from individuals or families with breast or ovarian cancer (Meindl 2002). The variant was identified in dbSNP (rs80357451) as “with uncertain significance allele”, ClinVar (classified as uncertain significance by BIC), LOVD 3.0 (observed 3x) and UMD-LSDB (observed 1x). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). In vitro expression of the variant had a demonstrable effect on BRCA1 transactivation activity but did not alter protein stability and binding; these discordant results led the authors to classify this variant as having an uncertain effect on protein function (Lee 2010). The p.Val1810 residue is conserved across mammals and other organisms, and 5 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.