ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1874_1877dupTAGT (p.Val627Serfs) (rs80357516)

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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 RCV000132134 SCV000187205 pathogenic Hereditary cancer-predisposing syndrome 2018-03-26 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) RCV000111711 SCV000144214 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 RCV000111711 SCV000325162 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Division Human Genetics,Medical University Innsbruck RCV000111711 SCV000211993 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111711 SCV000299661 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 RCV000047615 SCV000209880 pathogenic not provided 2018-09-06 criteria provided, single submitter clinical testing This duplication of four nucleotides in BRCA1 is denoted c.1874_1877dupTAGT at the cDNA level and p.Val627SerfsX4 (V627SfsX4) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is GAAC[dupTAGT]AGTC. The duplication causes a frameshift, which changes a Valine to a Serine at codon 627, and creates a premature stop codon at position 4 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.1874_1877dupTAGT, previously reported as 1997insTAGT or 1966insTAGT, has been observed in several individuals with personal and/or family histories consistent with hereditary breast and ovarian cancer syndrome (Balz 2002, Thomassen 2008, Bellacosa 2010, Kwong 2012). Based on currently available evidence, we consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785208 SCV000923776 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000167828 SCV000698894 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-25 criteria provided, single submitter clinical testing
Invitae RCV000167828 SCV000075628 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val627Serfs*4) 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 reported in an individual affected with breast cancer and an individual affected with breast and/or ovarian cancer (PMID: 12505256, 22970155). This sequence change is also known as 1996insTAGT in the literature. ClinVar contains an entry for this variant (Variation ID: 54376). 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 RCV000111711 SCV000195895 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000047615 SCV000296276 pathogenic not provided 2014-12-15 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000167828 SCV000587165 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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