ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2199del (p.Lys734fs) (rs80357944)

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Total submissions: 10
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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) RCV000077095 SCV000299715 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 RCV000235485 SCV000292511 pathogenic not provided 2018-11-23 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2199delG at the cDNA level and p.Lys734AsnfsX2 (K734NfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is AAGA[G]AAAC. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 734, and creates a premature stop codon at position 2 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.2199delG, previously reported as 2318delG, has been observed in association with pancreatic and breast cancer (Al-Sukhni 2008, Golan 2014) and is reported in the Breast Cancer Information Core (BIC) database as clinical important. We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077095 SCV000325285 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077095 SCV000786107 pathogenic Breast-ovarian cancer, familial 1 2018-02-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235485 SCV000887639 pathogenic not provided 2018-06-27 criteria provided, single submitter clinical testing
Color RCV000771401 SCV000903749 pathogenic Hereditary cancer-predisposing syndrome 2018-01-22 criteria provided, single submitter clinical testing
Invitae RCV000496526 SCV000958701 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys734Asnfs*2) 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 several individuals affected with breast cancer (PMID: 26681682, 29446198) and an individual affected with pancreatic cancer (PMID: 18762988). ClinVar contains an entry for this variant (Variation ID: 91578). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077095 SCV000108892 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077095 SCV000144332 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 RCV000496526 SCV000587198 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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