Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000112085 | SCV000282305 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-04-22 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000112085 | SCV000296363 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-07-10 | criteria provided, single submitter | clinical testing | |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112085 | SCV000325647 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226181 | SCV003923026 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-03-27 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.3397_3398delTT (p.Leu1133ArgfsX7) 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 250824 control chromosomes (gnomAD). c.3397_3398delTT has been reported in the literature in individuals with a personal and/or family history of breast and/or ovarian cancers (e.g. Sekine_2001, Rebbeck_2018, Yoshihara_2011). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three submitters, including an expert panel (ENIGMA) have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV003226181 | SCV004296819 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1133Argfs*7) 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 premature translational stop signal has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 11695708, 31825140). This variant is also known as 3516-3517delTT. ClinVar contains an entry for this variant (Variation ID: 54865). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Breast Cancer Information Core |
RCV000112085 | SCV000144749 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
| Laboratory for Genotyping Development, |
RCV003162407 | SCV002758469 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |