Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031058 | SCV000299793 | 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. |
Gene |
RCV000235126 | SCV000210133 | pathogenic | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | Nonsense 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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Identified in several individuals with breast and/or ovarian cancer (Liede 2002, Dworkin 2009, Walsh 2011, De Leeneer 2012, Rashid 2016); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2722C>G; This variant is associated with the following publications: (PMID: 19340607, 25525159, 16818684, 22006311, 17851763, 23725378, 21553119, 27553291, 27767231, 12181777, 29446198, 30720243, 30322717, 31528241, 33654310, 32341426) |
Ambry Genetics | RCV000162858 | SCV000213345 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-26 | criteria provided, single submitter | clinical testing | The p.S868* pathogenic mutation (also known as c.2603C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2603. This changes the amino acid from a serine to a stop codon within coding exon 9. This mutation has been reported in multiple breast and/or ovarian cancer families across several ethnicities (Li WF et al. Breast Cancer Res. Treat. 2008 Jul;110(1):99-109; Liede A et al. Am. J. Hum. Genet. 2002 Sep;71(3):595-606; Walsh T et al. Proc. Natl. Acad. Sci. U.S.A. 2011 Nov;108(44):18032-7; Rashid MU et al. BMC Cancer. 2016 Aug;16:673). Of note, this alteration is also designated as 2722C>G 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000235126 | SCV000296451 | pathogenic | not provided | 2023-01-25 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of BRCA1 protein synthesis. The frequency of this variant in the general population, 0.000004 (1/251118 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 32341426 (2020), 31528241 (2019), 30322717 (2018), 22006311 (2011), 17445839 (2007), 12181777 (2002)). Based on the available information, this variant is classified as pathogenic. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000031058 | SCV000325405 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000031058 | SCV000489349 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496687 | SCV000698970 | pathogenic | Hereditary breast ovarian cancer syndrome | 2016-04-18 | criteria provided, single submitter | clinical testing | Variant summary: The c.2603C>G variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.2675T>A, p.Leu892X; c.2679_2682delGAAA; p.Lys893fsX106; c.2722G>T, p.Glu908X). The variant is absent from the large, broad ExAC control population, but has been reported in numerous affected individuals in the literature. Multiple reputable clinical labs have classified the variant as "pathogenic". Therefore, this variant has been classified as a Pathogenic. |
Color Diagnostics, |
RCV000162858 | SCV001351491 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | 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. This variant has been identified in 1/251118 chromosomes 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 | RCV000496687 | SCV001592831 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser868*) 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 present in population databases (rs80356925, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 12181777, 21553119, 22006311, 26681312, 27553291). This variant is also known as 2722C>G, p.Ser868X. ClinVar contains an entry for this variant (Variation ID: 37477). For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000235126 | SCV002024689 | pathogenic | not provided | 2019-01-15 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162858 | SCV002538140 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-18 | criteria provided, single submitter | curation | |
Sharing Clinical Reports Project |
RCV000031058 | SCV000053653 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2009-07-20 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031058 | SCV000144488 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496687 | SCV000587236 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
BRCAlab, |
RCV000031058 | SCV004244084 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |