Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112043 | SCV000299905 | 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. |
Ambry Genetics | RCV000165817 | SCV000216564 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-03-20 | criteria provided, single submitter | clinical testing | The c.3279delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 3279, causing a translational frameshift with a predicted alternate stop codon (p.Y1094Ifs*15). This mutation has been identified in one HBOC kindred of Dutch descent as well as in one HBOC kindred of Moroccan descent in which the proband and her mother were diagnosed with breast cancer at ages 32 and 49, respectively (van der Hout AH et al. Hum. Mutat., 2006 Jul;27:654-66; Tazzite A et al. Gynecol. Oncol., 2012 Jun;125:687-92). In addition 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000112043 | SCV000296428 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-02-17 | criteria provided, single submitter | clinical testing | |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112043 | SCV000325596 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000482423 | SCV000568416 | pathogenic | not provided | 2021-02-03 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with breast and/or ovarian cancer (Tazzite 2012, El Ansari 2020); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed in large population cohorts (Lek 2016); Also known as 3398delC; This variant is associated with the following publications: (PMID: 23289006, 16683254, 25814778, 25885115, 23697973, 24606420, 22425665, 32778078, 30263132) |
Labcorp Genetics |
RCV001387922 | SCV001588679 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-01-03 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 11897832, 16683254, 22425665). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54816). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1094Ilefs*15) 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). |
Breast Cancer Information Core |
RCV000112043 | SCV000144696 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-05-24 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000499817 | SCV000591434 | pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Tyr1094IlefsX15 deletion variant was identified in 2 of 942 proband chromosomes (frequency 0.002) from Moroccan or Dutch breast and/or ovarian cancer families (Tazzite 2012, van der Hout 2006). The variant was also identified in HGMD, UMD (4X as a causal variant), and once in the BIC database as a variant with clinical importance. The p.Tyr1094IlefsX15 deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1094 and leads to a premature stop codon 15 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. | |
Foulkes Cancer Genetics LDI, |
RCV000735519 | SCV000863657 | pathogenic | Breast and/or ovarian cancer | 2013-08-16 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000482423 | SCV001740845 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000482423 | SCV001906243 | pathogenic | not provided | no assertion criteria provided | clinical testing |