Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112628 | SCV000300247 | 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112628 | SCV000326288 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000496764 | SCV002157235 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-02-16 | criteria provided, single submitter | clinical testing | A different truncation (p.Tyr1853*) that lies downstream of this variant has been determined to be pathogenic (PMID: 21922593, 10811118, 11739404, 12400015, 7894493, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant disrupts the C-terminal end of the BRCA1 protein partially including the BRCT domain (residues 1646-1859), which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While functional studies have not been performed to directly test the effect on BRCA1 protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. ClinVar contains an entry for this variant (Variation ID: 125832). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1785Thrfs*45) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acid(s) of the BRCA1 protein. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002345407 | SCV002641528 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-18 | criteria provided, single submitter | clinical testing | The c.5352dupA variant, located in coding exon 20 of the BRCA1 gene, results from a duplication of A at nucleotide position 5352, causing a translational frameshift with a predicted alternate stop codon (p.Q1785Tfs*45). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of BRCA1, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 35 amino acids of the protein. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998230 | SCV005626144 | pathogenic | not provided | 2024-10-02 | criteria provided, single submitter | clinical testing | The BRCA1 c.5352dup (p.Gln1785Thrfs*45) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in an individual with breast cancer (PMID: 33573335 (2021)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |
Breast Cancer Information Core |
RCV000112628 | SCV000145477 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496764 | SCV000587502 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research |