ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3106T>C (p.Phe1036Leu) (rs766381694)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254861 SCV000321426 uncertain significance not provided 2016-07-11 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3106T>C at the cDNA level, p.Phe1036Leu (F1036L) at the protein level, and results in the change of a Phenylalanine to a Leucine (TTT>CTT). Using alternate nomenclature, this variant would be defined as BRCA1 3225T>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Phe1036Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Phenylalanine and Leucine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Phe1036Leu occurs at a position that is not conserved and is located within the DNA binding domain and a region known to interact with RAD51 (Chen 1998, Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Phe1036Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000551637 SCV000635883 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-02 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 1036 of the BRCA1 protein (p.Phe1036Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs766381694, ExAC 0.001%) but has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 265049). 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 leucine 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. In summary, this variant is a rare missense change that is not predicted to affect 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.

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.