ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3703C>T (p.Gln1235Ter) (rs1555283366)

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 RCV000657710 SCV000779459 pathogenic not provided 2017-03-08 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3703C>T at the cDNA level and p.Gln1235Ter (Q1235X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000781127 SCV000918975 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3703C>T (p.Gln1235X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.3744_3747delTGAG, p.Ser1248fsX10; c.3785C>A, p.Ser1262X; c.3847_3848delGT, p.Val1283fsX2). The variant was absent in 120326 control chromosomes. To our knowledge, no occurrence of c.3703C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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.