ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1556del (p.Lys519fs) (rs80357662)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129703 SCV000184504 pathogenic Hereditary cancer-predisposing syndrome 2017-12-19 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) RCV000019255 SCV000144130 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129703 SCV000682972 pathogenic Hereditary cancer-predisposing syndrome 2015-06-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000019255 SCV000325099 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000019255 SCV000564334 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496710 SCV000591341 pathogenic Hereditary breast and ovarian cancer syndrome 2012-11-19 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000019255 SCV000299620 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 RCV000235933 SCV000292509 pathogenic not provided 2017-09-25 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.1556delA at the cDNA level and p.Lys519ArgfsX13 (K519RfsX13) at the protein level. The normal sequence, with the deleted base in brackets, is ATCA[delA]GAAA. The deletion causes a frameshift, which changes a Lysine to an Arginine at codon 519, and creates a premature stop codon at position 13 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.1556delA, previously reported as 1675delA, has been observed in association with breast and ovarian cancer and is considered to be a Norwegian pathogenic founder variant (H?berg-Vetti 2015, Johannsson 1996, Borg 1999, Janavicius 2010). Based on current evidence, we consider this variant to be pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000019255 SCV000839889 pathogenic Breast-ovarian cancer, familial 1 2017-05-25 criteria provided, single submitter clinical testing The c.1556del (p.Lys519Argfs*13) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8644702, 26718727, 24504028, 18559594, referred as aka 1675delA in some publications]. This variant is a founder mutation in the Swedish population [PMID 8644702]. This one bp deletion in exon 2 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic
Integrated Genetics/Laboratory Corporation of America RCV000496710 SCV000698874 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1556delA (p.Lys519Argfs) 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.1621C>T [p.Gln541X], c.1674delA [p.Gly559fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in the large control database ExAC (0/120854 control chromosomes). The variant has been cited in the literature in breast cancer or ovarian cancer patients numerous times (was identified in at least 20 patients in Judkins_Cancer Res_2005) and is considered a founder mutation in northern Europeans (e.g., see Hoberg-Vetti_BRCA_EJHG_2016 and Soegaard_BRCA1&2_CCR_2008). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
OMIM RCV000019255 SCV000039543 pathogenic Breast-ovarian cancer, familial 1 1999-09-01 no assertion criteria provided literature only
Pathway Genomics RCV000019255 SCV000189883 pathogenic Breast-ovarian cancer, familial 1 2014-07-24 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235933 SCV000296362 pathogenic not provided 2015-07-14 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496710 SCV000587147 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000019255 SCV000053595 pathogenic Breast-ovarian cancer, familial 1 2011-05-09 no assertion criteria provided clinical testing

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