ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2813C>T (p.Pro938Leu) (rs1064793999)

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 RCV000482849 SCV000567549 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2813C>T at the cDNA level, p.Pro938Leu (P938L) at the protein level, and results in the change of a Proline to a Leucine (CCA>CTA). Using alternate nomenclature, this variant would be defined as BRCA1 2932C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Pro938Leu 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 Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Pro938Leu occurs at a position that is not conserved and is located in the DNA binding domain and the region of interaction with BASC and RAD51 (Chen 1998, Narod 2004). 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 Pro938Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000541701 SCV000635867 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-03-10 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 938 of the BRCA1 protein (p.Pro938Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. 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. 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 novel 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.