ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2603C>G (p.Ser868Ter)

dbSNP: rs80356925
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) 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.
GeneDx 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 (CIMBA), c/o University of Cambridge 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, LabCorp 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, LLC DBA Color Health 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, Revvity Omics RCV000235126 SCV002024689 pathogenic not provided 2019-01-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000162858 SCV002538140 pathogenic Hereditary cancer-predisposing syndrome 2021-10-18 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031058 SCV000053653 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2009-07-20 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031058 SCV000144488 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496687 SCV000587236 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
BRCAlab, Lund University RCV000031058 SCV004244084 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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