Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000111561 | SCV000299549 | 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 |
RCV000111561 | SCV000324967 | 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, |
RCV000779890 | SCV000916780 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-07-11 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1141A>T (p.Lys381X) 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 245912 control chromosomes (gnomAD). The variant, c.1141A>T, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer ((Garcia-Patino_1998, Lang_2017, Rebbeck_2018, Shi_2017, Keshavarzi_2013). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000779890 | SCV002198593 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys381*) 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: 9664122, 21918854, 28176296, 28294317, 29446198). This variant is also known as 1260A>T. ClinVar contains an entry for this variant (Variation ID: 54145). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002453357 | SCV002616903 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-14 | criteria provided, single submitter | clinical testing | The p.K381* pathogenic mutation (also known as c.1141A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1141. This changes the amino acid from a lysine to a stop codon within coding exon 9. This mutation has been reported in multiple hereditary breast and ovarian cancer (HBOC) cohorts (Garcia-Patiño E et al. Acta Oncol, 1998;37:299-300; Cheung LW et al. FEBS Lett, 2007 Oct;581:4668-74; Keshavarzi F et al. Fam Cancer, 2012 Mar;11:57-67; Lang GT et al. Int J Cancer, 2017 07;141:129-142; Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Copson ER et al. Lancet Oncol, 2018 02;19:169-180; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). Of note, this alteration is also designated as A1260T in published literature. 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. |
| Color Diagnostics, |
RCV002453357 | SCV004361076 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A functional study has shown that the variant causes altered protein expression, decreased homologous repair efficiency, and an increased level of chromosomal aberrations compared to wild type (PMID: 34855882). 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. |
| Breast Cancer Information Core |
RCV000111561 | SCV000144024 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2007-01-18 | no assertion criteria provided | clinical testing |