ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.124A>G (p.Ile42Val) (rs80357163)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000590608 SCV000075403 likely benign not provided 2016-08-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175357 SCV000698840 uncertain significance not specified 2019-10-03 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.124A>G (p.Ile42Val) results in a conservative amino acid change located in the RING-type zinc finger domain of the encoded protein sequence (IPR001841). Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250738 control chromosomes (gnomAD). To our knowledge, no occurrence of c.124A>G in individuals affected with Hereditary Breast and Ovarian Cancer has been reported in the literature. Several publications reported experimental evidence evaluating an impact on protein function and found that the I42V variant protein retains the E3 ligase-, SSA- and HDR activity; the variant does not impact BARD1- and UbcH5a binding, but slightly decreases cell survival upon radiation. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Color Health, Inc RCV000775195 SCV000909421 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-23 criteria provided, single submitter clinical testing
Invitae RCV001398773 SCV001600548 likely benign Hereditary breast and ovarian cancer syndrome 2016-08-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083167 SCV000115241 uncertain significance Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083167 SCV000144379 uncertain significance Breast-ovarian cancer, familial 1 1999-03-24 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000083167 SCV001237892 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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