Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410713 | SCV000489381 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001039562 | SCV001203094 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu290*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371981). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001039562 | SCV001364037 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-10-29 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.869T>A (p.Leu290X) 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 251130 control chromosomes (gnomAD). To our knowledge, no occurrence of c.869T>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. However, another variant at this position, c.869T>G, likewise resulting in truncation of the BRCA1 protein (p.Leu290X), has been observed in individuals affected with Hereditary Breast and Ovarian Cancer (e.g. PMID: 26681312, PMID: 29446198) and has been cited as pathogenic in ClinVar (reviewed by expert panel, ENIGMA). A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Ambry Genetics | RCV002374614 | SCV002684131 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-12-13 | criteria provided, single submitter | clinical testing | The p.L290* pathogenic mutation (also known as c.869T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 869. This changes the amino acid from a leucine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Baylor Genetics | RCV000410713 | SCV004212763 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-09-14 | criteria provided, single submitter | clinical testing |