Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000241023 | SCV000299520 | 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 | RCV000165859 | SCV000216608 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-21 | criteria provided, single submitter | clinical testing | The p.K338* pathogenic mutation (also known as c.1012A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1012. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Copson ER et al. Lancet Oncol, 2018 02;19:169-180; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Deng H et al. Mol Genet Genomic Med, 2019 06;7:e672). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000241023 | SCV000324927 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000241023 | SCV000677718 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-03-29 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000165859 | SCV000682930 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-04-27 | 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. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in at least three individuals affected with breast and ovarian cancer and a suspected hereditary breast cancer family (PMID: 20127978, 29681614, 30972954; Color internal data). 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. |
| Labcorp Genetics |
RCV000496572 | SCV001587270 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys338*) 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 a personal and/or family history of breast and/or ovarian cancer (PMID: 15998910, 28176296, 29446198, 29681614). This variant is also known as 1131A>T. ClinVar contains an entry for this variant (Variation ID: 54101). For these reasons, this variant has been classified as Pathogenic. |
| Research Molecular Genetics Laboratory, |
RCV000496572 | SCV000587092 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research |