ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3746C>G (p.Thr1249Ser) (rs80357099)

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
GeneDx RCV000485104 SCV000571437 uncertain significance not provided 2017-09-21 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3746C>G at the cDNA level, p.Thr1249Ser (T1249S) at the protein level, and results in the change of a Threonine to a Serine (ACC>AGC). Using alternate nomenclature, this variant would be defined as BRCA1 3865C>G. This variant has been reported in at least one individual undergoing clinical testing for hereditary breast and ovarian cancer syndrome (Abkevich 2004). BRCA1 Thr1249Ser was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Thr1249Ser occurs at a position that is not conserved 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 evidence, it is unclear whether BRCA1 Thr1249Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562072 SCV000665876 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000112169 SCV000144856 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.