Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000257187 | SCV000323361 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-10-18 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Invitae | RCV000047604 | SCV000075617 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 19656164, 22798144). ClinVar contains an entry for this variant (Variation ID: 54366). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu611*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000257187 | SCV000325157 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001013319 | SCV001173894 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-05 | criteria provided, single submitter | clinical testing | The c.1831delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1831, causing a translational frameshift with a predicted alternate stop codon (p.L611*). This alteration has been reported in multiple breast and/or ovarian cancer patients from Korea (Seong MW et al. Clin. Genet. 2009 Aug;76:152-60; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134:1315-26; Kang E et al. Breast Cancer Res. Treat. 2015 May;151:157-68; Kim DH et al. J Gynecol Oncol. 2018 Nov;29:e90; Kwon BS et al. Cancer Res Treat. 2018 Oct). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families, specifically in two families from Korea (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). In addition to the clinical data presented in the literature, 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. |