Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000077067 | SCV000299588 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280941 | SCV001468291 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-12-25 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1377_1378delAA (p.Lys459AsnfsX20) 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. The variant was absent in 251080 control chromosomes. To our knowledge, no occurrence of c.1377_1378delAA in individuals affected with Hereditary Breast And Ovarian Cancer (HBOC) and no experimental evidence demonstrating its impact on protein function have been reported. Other loss of function variants in the vicinity of this variant have been observed in the setting of HBOC. One expert panel (ENIGMA) has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001280941 | SCV001591167 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-04-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys459Asnfs*20) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 91550). This variant is not present in population databases (ExAC no frequency). |
| Sharing Clinical Reports Project |
RCV000077067 | SCV000108864 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-05-25 | no assertion criteria provided | clinical testing |