ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1061C>T (p.Thr354Ile)

gnomAD frequency: 0.00001  dbSNP: rs776939714
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
Ambry Genetics RCV000214947 SCV000273707 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-04 criteria provided, single submitter clinical testing The p.T354I variant (also known as c.1061C>T), located in coding exon 7 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1061. The threonine at codon 354 is replaced by isoleucine, an amino acid with similar properties. In one study, this alteration was observed in 1/3236 cases with invasive epithelial ovarian cancer and 0/3431 controls (Ramus SJ et al. J. Natl. Cancer Inst., 2015 Nov;107). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001044759 SCV001208574 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-07-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 354 of the BRIP1 protein (p.Thr354Ile). This variant is present in population databases (rs776939714, gnomAD 0.004%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 230240). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354).
Color Diagnostics, LLC DBA Color Health RCV000214947 SCV001355679 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 354 of the BRIP1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/282730 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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.