ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2912A>G (p.His971Arg) (rs1567793641)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV001003376 SCV001161498 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 = 0.000194
Color RCV000772921 SCV000906303 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-12 criteria provided, single submitter clinical testing
Invitae RCV000817352 SCV000957906 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-08-16 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 971 of the BRCA1 protein (p.His971Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with breast cancer (PMID: 29021639, 21520333). This variant is also known as G3031A in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.