ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2603C>G (p.Ser868Ter) (rs80356925)

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Total submissions: 11
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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 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 2018-02-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2603C>G at the cDNA level and p.Ser868Ter (S868X) at the protein level. The substitution creates a nonsense variant, changing a Serine to a premature stop codon (TCA>TGA). BRCA1 Ser868Ter is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also denoted 2722C>G using alternate nomenclature, has been identified in several individuals with breast and/or ovarian cancer (Liede 2002, Dworkin 2009, Walsh 2011, De Leeneer 2012). Additionally, the C>A substitution at nucleotide 2603, alternatively known as BRCA1 2722C>A, also results in the a premature stop codon and has been reported in at least one individual with a history of early onset breast cancer (Li 2008). Based on currently available evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000162858 SCV000213345 pathogenic Hereditary cancer-predisposing syndrome 2018-11-06 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235126 SCV000296451 pathogenic not provided 2016-04-08 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031058 SCV000325405 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031058 SCV000489349 pathogenic Breast-ovarian cancer, familial 1 2016-09-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496687 SCV000698970 pathogenic Hereditary breast and 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 RCV000162858 SCV001351491 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031058 SCV000053653 pathogenic Breast-ovarian cancer, familial 1 2009-07-20 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031058 SCV000144488 pathogenic Breast-ovarian cancer, familial 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 and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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