ClinVar Miner

Submissions for variant NM_007298.3(BRCA1):c.788-1063_788-1060del (rs397509067)

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Total submissions: 11
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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) RCV000077549 SCV000299942 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048197 SCV000076210 pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-12 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotide from exon 10 of the BRCA1 mRNA (c.3436_3439delTGTT), causing a frameshift at codon 1146. This creates a premature translational stop signal (p.Cys1146Leufs*8) 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 the literature in individuals affected with breast and/or ovarian cancer (PMID: 10644434, 22798144, 25452441, 22923021). This variant is also known as 3555del4 in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneKor MSA RCV000239029 SCV000296796 pathogenic not specified 2016-07-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000459696 SCV000540937 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000478411 SCV000564734 pathogenic not provided 2014-12-08 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.3436_3439delTGTT at the cDNA level and p.Cys1146LeufsX8 at the protein level. This variant, also known as BRCA1 3555del4 using alternate nomenclature, has been reported as a pathogenic variant (Wagner 1999, Audeh 2010, Novakovic 2012). The normal sequence with the bases that are deleted in brackets is GGTT[TGTT]CTGA. The deletion cases a frameshift,which changes a Cysteine to a Leucine at codon 1146, and introduces a premature stop codon at position 8 of the new reading frame. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000077549 SCV000575719 pathogenic Breast-ovarian cancer, familial 1 2015-08-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048197 SCV000591446 pathogenic Hereditary breast and ovarian cancer syndrome 2012-12-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509977 SCV000607790 pathogenic Hereditary cancer-predisposing syndrome 2017-07-14 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)
Counsyl RCV000077549 SCV000677719 pathogenic Breast-ovarian cancer, familial 1 2016-11-28 criteria provided, single submitter clinical testing
Color RCV000509977 SCV000683107 pathogenic Hereditary cancer-predisposing syndrome 2017-03-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077549 SCV000109350 pathogenic Breast-ovarian cancer, familial 1 2012-07-06 no assertion criteria provided clinical testing

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