ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3858_3861del (p.Ser1286fs) (rs80357842)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509638 SCV000608083 pathogenic Hereditary cancer-predisposing syndrome 2015-10-12 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) RCV000031134 SCV000144902 pathogenic Breast-ovarian cancer, familial 1 1997-11-14 no assertion criteria provided clinical testing
Color RCV000509638 SCV000683138 pathogenic Hereditary cancer-predisposing syndrome 2016-08-05 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031134 SCV000325773 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031134 SCV000489367 pathogenic Breast-ovarian cancer, familial 1 2016-09-26 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031134 SCV000300031 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000048359 SCV000699077 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-07 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3858_3861delTGAG (p.Ser1286Argfs) 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.3868A>T (p.Lys1290X), c.3869_3870delAA (p.Lys1290fs), and c.3893C>A (p.Ser1298X; c.3904G>T)). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121396 control chromosomes (ExAC). Multiple publications have cited the variant in affected individuals (BrC, OvC, HBOC). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048359 SCV000076372 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-23 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 10 of the BRCA1 mRNA (c.3858_3861delTGAG), causing a frameshift at codon 1286. This creates a premature translational stop signal (p.Ser1286Argfs*20) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in individuals affected with breast cancer/ovarian cancer (PMID: 10874312, 20859677, 26187060). This variant is also known as 3976-3979delGTGA and 3977del4 in the literature. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508686 SCV000605856 pathogenic not provided 2017-03-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031134 SCV000053733 pathogenic Breast-ovarian cancer, familial 1 2007-03-02 no assertion criteria provided clinical testing

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