Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000238667 | SCV000323316 | 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000238667 | SCV000325063 | 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, |
RCV000496818 | SCV000918671 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-10-16 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1407_1408delAA (p.Ser470ProfsX9) 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. The variant was absent in 251228 control chromosomes. c.1407_1408delAA has been reported in the literature in individuals affected with breast cancer (e.g. Chavarri-Guerra_2022). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35438911). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000496818 | SCV001235838 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 252863). This sequence change creates a premature translational stop signal (p.Ser470Profs*9) 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 breast and/or ovarian cancer (PMID: 29446198). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002392750 | SCV002698911 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | The c.1407_1408delAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 1407 to 1408, causing a translational frameshift with a predicted alternate stop codon (p.S470Pfs*9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Fulgent Genetics, |
RCV002479951 | SCV002800163 | pathogenic | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2022-04-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003165676 | SCV003915199 | pathogenic | not provided | 2022-10-10 | 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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1526_1527del |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003165676 | SCV004222564 | pathogenic | not provided | 2022-06-24 | criteria provided, single submitter | clinical testing | This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in one or more individual(s) with triple negative breast cancer (PMID: 35438911 (2022)). Based on the available information, this variant is classified as pathogenic. |
Sharing Clinical Reports Project |
RCV000238667 | SCV000297466 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-11-12 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496818 | SCV000587133 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research |