ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2397T>A (p.Asn799Lys) (rs80357203)

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
Invitae RCV000047824 SCV000075837 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 799 of the BRCA1 protein (p.Asn799Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 54556). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000164929 SCV000215618 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768615 SCV000324812 uncertain significance Breast and/or ovarian cancer 2015-11-09 criteria provided, single submitter clinical testing
Counsyl RCV000111842 SCV000488092 uncertain significance Breast-ovarian cancer, familial 1 2015-12-23 criteria provided, single submitter clinical testing
Color RCV000164929 SCV000683031 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587218 SCV000698947 uncertain significance not provided 2017-04-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2397T>A (p.Asn799Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). The variant of interest is absent in the large, broad control population, ExAC in 121334 control chromosomes. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. This variant is reported in UMD-BRCA1 in 4 patients and in 2 as co-occurring with a variant classified by UMD as pathogenic (c.5144G>A; p.Ser171Asn). At this time LCA did not classify this variant and as such these co-occurrences were not included. Because of the paucity of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587218 SCV000888864 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111842 SCV000144406 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 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.