ClinVar Miner

Submissions for variant NM_007298.3(BRCA1):c.787+353dup (rs876659327)

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Total submissions: 6
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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) RCV000661341 SCV000783611 pathogenic Breast-ovarian cancer, familial 1 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000216621 SCV000275674 pathogenic Hereditary cancer-predisposing syndrome 2018-03-06 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)
GeneDx RCV000235683 SCV000292732 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.1140dupG at the cDNA level and p.Lys381GlufsX3 (K381EfsX3) at the protein level. Using alternate nomenclature, this variant is also known as BRCA1 1259dupG. The normal sequence, with the base that is duplicated in brackets, is TTCA[dupG]AAAG. The duplication causes a frameshift, which changes a Lysine to a Glutamic Acid at codon 381 and creates a premature stop codon at position 3 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. This variant has been reported in multiple individuals with breast or ovarian cancer, and has been described as a recurrent variant in Saudi Arabia (Bu 2016, Yang 2017, Alhuqail 2018). Based on currently available evidence, we consider this variant to be pathogenic.
GeneKor MSA RCV000235683 SCV000693507 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Invitae RCV000810943 SCV000951185 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys381Glufs*3) 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 and ovarian cancer (PMID: 27082205, 29297111, 28664506). ClinVar contains an entry for this variant (Variation ID: 231732). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000408852 SCV000484954 likely pathogenic Familial cancer of breast no assertion criteria provided clinical testing

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