ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3776A>C (p.Asn1259Thr) (rs483353090)

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 RCV000159849 SCV000209893 uncertain significance not provided 2014-07-14 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3776A>C at the cDNA level, p.Asn1259Thr (N1259T) at the protein level, and results in the change of an Asparagine to a Threonine (AAT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Asn1259Thr 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 Asparagine and Threonine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Asn1259Thr occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA1 Asn1259Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000204460 SCV000259957 benign Hereditary breast and ovarian cancer syndrome 2017-11-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112181 SCV000296461 uncertain significance Breast-ovarian cancer, familial 1 2016-04-26 criteria provided, single submitter clinical testing
Color RCV000771318 SCV000903576 likely benign Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779862 SCV000916731 uncertain significance not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3776A>C (p.Asn1259Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.3e-05 in 245960 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (3.3e-05 vs 1.00e-03), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3776A>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign and the other laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112181 SCV000144876 uncertain significance Breast-ovarian cancer, familial 1 2013-03-25 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.