Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000661316 | SCV000783583 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Color Diagnostics, |
RCV001182956 | SCV001348567 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-08 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 14 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Invitae | RCV000501033 | SCV001374637 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-03-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1556*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). 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 not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 433717). |
| Ambry Genetics | RCV001182956 | SCV002638111 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-17 | criteria provided, single submitter | clinical testing | The p.Q1556* pathogenic mutation (also known as c.4666C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4666. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant has been observed in breast and ovarian cancer cohorts (Oros KK et al. Int J Cancer, 2004 Nov;112:411-9; Borg A et al. Hum Mutat, 2010 Mar;31:E1200-40; Lhotova K et al. Cancers (Basel), 2020 Apr;12). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). 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. |
| Baylor Genetics | RCV000661316 | SCV004216860 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-12-27 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000661316 | SCV000591532 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | The p.Gln1556X variant has not been reported in the literature. The variant leads to a premature stop codon at position 1556 which is predicted to cause premature truncation of the protein product. This is a loss of function DNA variant and loss of function is an established disease mechanism for the BRCA1 gene in hereditary breast and ovarian cancer. In summary, based on the above information, this variant is classified as pathogenic. | |
| CZECANCA consortium | RCV001271026 | SCV001451840 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |