ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1480C>T (p.Gln494Ter) (rs80357010)

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Total submissions: 13
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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) RCV000030996 SCV000299605 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047490 SCV000075503 pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln494*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and ovarian cancer (PMID: 10866029, 25066507, 26187060,25863477). This variant is also known as 1599C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37415). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000030996 SCV000195891 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000223308 SCV000275584 pathogenic Hereditary cancer-predisposing syndrome 2018-11-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000030996 SCV000296334 pathogenic Breast-ovarian cancer, familial 1 2015-05-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000030996 SCV000325078 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000030996 SCV000487901 pathogenic Breast-ovarian cancer, familial 1 2015-12-10 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000047490 SCV000605760 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-11 criteria provided, single submitter clinical testing The p.Gln494X variant in BRCA1 has been identified in >5 individuals with BRCA1- associated cancers (Peyrat 1998, Kim 2012, Breast Cancer Information Core (BIC) database) and was absent from large population studies. This nonsense variant le ads to a premature termination codon at position 494, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 ge ne is an established disease mechanism in hereditary breast and ovarian cancer ( HBOC). Furthermore, this variant was classified as Pathogenic on Sept 8, 2016 by the ClinGen-approved ENIGMA Expert Panel (ClinVar SCV000299605.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autoso mal dominant manner.
GeneDx RCV000657593 SCV000779331 pathogenic not provided 2018-03-12 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1480C>T at the cDNA level and p.Gln494Ter (Q494X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as 1599C>T using alternate nomenclature, has been reported in multiple individuals with Hereditary Breast and Ovarian Cancer (Peyrat 1998, Judkins 2005, Kim 2012, Janavicius 2014, Kang 2015, Park 2017) and is considered pathogenic.
Color RCV000223308 SCV001351492 pathogenic Hereditary cancer-predisposing syndrome 2019-08-22 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000030996 SCV000053588 pathogenic Breast-ovarian cancer, familial 1 2011-07-19 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000030996 SCV000144107 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 RCV000047490 SCV000587140 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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