ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.134+1G>C (rs80358043)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589448 SCV000698848 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.134+1G>C variant involves the alteration of a conserved intronic nucleotide at a position known to affect splicing with 5/5 splice prediction tools predict the loss of a splicing site and ESE finder predicts alterations to ESE binding, however, these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. However, a reputable database with a classification from 2002 cites the variant as "pathogenic." In addition, other variants located at this position, c.134+1G>A and c.134+1G>T, have been cited as "pathogenic." Therefore, the variant of interest has been classified as a "Likely Pathogenic" variant until additional information confirming the co-segregation with disease and an in-vitro/in-vivo impact on splicing are obtained.
Invitae RCV000589448 SCV001209577 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 125563). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30209399). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111847 SCV000144413 pathogenic Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000111847 SCV001241928 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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