ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3668_3671dupTTCC (p.Cys1225Serfs) (rs80357797)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129597 SCV000184381 pathogenic Hereditary cancer-predisposing syndrome 2016-04-19 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) RCV000112152 SCV000144833 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129597 SCV000688446 pathogenic Hereditary cancer-predisposing syndrome 2017-08-14 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112152 SCV000325718 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048279 SCV000591462 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112152 SCV000282313 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735459 SCV000863596 pathogenic Breast and/or ovarian cancer no assertion criteria provided clinical testing
GeneDx RCV000159921 SCV000210045 pathogenic not provided 2018-10-01 criteria provided, single submitter clinical testing This duplication of four nucleotides in BRCA1 is denoted c.3668_3671dupTTCC at the cDNA level and p.Cys1225SerfsX10 (C1225SfsX10) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is GAGC[dupTTCC]CTGC. The duplication causes a frameshift, which changes a Cysteine to a Serine at codon 1225 and creates a premature stop codon at position 10 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.3668_3671dupTTCC, previously reported as c.3671_3672insTTCC, 3790insTTCC, and 3790ins4, has been published as a pathogenic variant and was observed in several individuals with a personal and/or family history suggestive of hereditary breast and ovarian cancer syndrome (Scottish/Northern Irish BRCA1/BRCA2 Consortium 2003, Claus 2005, Alsop 2012). We consider this variant to be pathogenic.
Invitae RCV000048279 SCV000076292 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys1225Serfs*10) 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 several individuals affected with breast and ovarian cancer (PMID: 12698193, 26718727, 22711857, 15728167). This variant is also known as 3790ins4 in the literature. ClinVar contains an entry for this variant (Variation ID: 54960). 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 RCV000159921 SCV000600340 pathogenic not provided 2016-09-26 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048279 SCV000587331 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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