ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1459G>T (p.Val487Phe) (rs369588942)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130777 SCV000185670 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130777 SCV000909382 likely benign Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing
Counsyl RCV000030995 SCV000488281 uncertain significance Breast-ovarian cancer, familial 1 2016-02-12 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000586346 SCV000859165 uncertain significance not provided 2018-01-09 criteria provided, single submitter clinical testing
GeneDx RCV000159870 SCV000209926 likely benign not specified 2018-01-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000586346 SCV000698866 uncertain significance not provided 2017-08-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1459G>T (p.Val487Phe) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 18/277044 control chromosomes in genomAD, predominantly observed in the African subpopulation at a frequency of 0.000749 (18/24032). This frequency is close to the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005), suggesting this is possibly a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance/likely benign, all without evidence for independent evaluation. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.
Invitae RCV000459454 SCV000549307 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 487 of the BRCA1 protein (p.Val487Phe). The valine residue is weakly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is present in population databases (rs369588942, ExAC 0.05%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 37414). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Sharing Clinical Reports Project (SCRP) RCV000030995 SCV000053587 likely benign Breast-ovarian cancer, familial 1 2010-09-03 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.