Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000258317 | SCV001161637 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-06-18 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.996657 |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000258317 | SCV000325973 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000585723 | SCV000693535 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-01-01 | criteria provided, single submitter | clinical testing | This variant is a single base pair deletion in the first base of intron 13 of the BRCA1 gene. This position is conserved in the human and other genomes and might be involved in mRNA processing. Therefore, this variant is expected to disrupt RNA splicing and results in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This variant has been reported in the literature in Turkish breast/ovarian families (PMID: 10952777). The mutation database ClinVar contains entries for this variant (Variation ID: 55211). |
| Labcorp Genetics |
RCV000585723 | SCV001574480 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-11-26 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with a personal and family history of breast and/or ovarian cancer (PMID: 10952777). This variant is also known as IVS-14+1delG in the literature. ClinVar contains an entry for this variant (Variation ID: 55211). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Genetics and Molecular Pathology, |
RCV000258317 | SCV002761620 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-12-31 | criteria provided, single submitter | clinical testing | The BRCA1 c.4484+1delG variant is classified as Pathogenic (PVS1, PM2, PP5) The BRCA1 c.4484+1delG variant is located in a splice donor region. Computational predictions support a deleterious effect on splicing and a likely disruption of the protein reading frame and non-sense mediated decay of the resulting protein product (PVS1).This variant is absent from population databases (PM2). not in population databases ENIGMA/Parsons 2019 co-segregation in ICON data from 1 family The variant has been reported in dbSNP (rs397509181) and in the HGMD database: CD004791. It has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 55211). Multifactorial analysis by ENIGMA consortium confirms this variant as pathogenic |