ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5335del (p.Gln1779fs) (rs80357590)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129334 SCV000184097 pathogenic Hereditary cancer-predisposing syndrome 2016-10-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031238 SCV000145468 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031238 SCV000326282 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048947 SCV000591617 pathogenic Hereditary breast and ovarian cancer syndrome 2012-10-01 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031238 SCV000300241 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 RCV000159930 SCV000210057 pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.5335delC at the cDNA level and p.Gln1779AsnfsX14 (Q1779NfsX14) at the protein level. The normal sequence, with the base that is deleted in brackets, is agAT[delC]AACT, where the capital letters are exonic and lowercase are intronic. The deletion causes a frameshift, which changes a Glutamine to an Asparagine at codon 1779, and creates a premature stop codon at position 14 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.5335delC, previously reported as 5454delC using alternate nomenclature, has been observed in multiple individuals with a personal and/or family history of breast and/or ovarian cancer (De Leon Matsuda 2002, Ibrahim 2010, Kuo 2012, Laraqui 2015, Yang 2017, Kwong 2018). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048947 SCV000699245 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5335delC (p.Gln1779Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5387C>A, p.Ser1796X; c.5417delC, p.Pro1806fs). One in silico tool predicts a damaging outcome for this variant and this variant is absent in 121004 control chromosomes. The variant has been reported in numerous patients in the literature and databases, and has been reported as a Filipino founder mutation. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048947 SCV000076960 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1779Asnfs*14) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 11920621, 26187060, 21324516). This variant is also known as 5454delC in the literature. ClinVar contains an entry for this variant (Variation ID: 37657). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031238 SCV000296292 pathogenic Breast-ovarian cancer, familial 1 2015-02-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159930 SCV000887723 pathogenic not provided 2015-02-19 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048947 SCV000587498 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031238 SCV000053842 pathogenic Breast-ovarian cancer, familial 1 2011-07-28 no assertion criteria provided clinical testing

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