Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000531474 | SCV000635776 | pathogenic | Hereditary breast ovarian cancer syndrome | 2017-03-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This sequence change deletes 2 nucleotides from exon 10 of the BRCA1 mRNA (c.1091_1092delCT), causing a frameshift at codon 364. This creates a premature translational stop signal (p.Pro364Glnfs*4) and is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000531474 | SCV000698831 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-05-15 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.1091_1092delCT (p.Pro364Glnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 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 (e.g. p.Gln1420X, p.Arg1443X, p.Glu1470X, etc.). This variant is absent in 121380 control chromosomes from ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as likely pathogenic. |