ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.115T>A (p.Cys39Ser) (rs80357164)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509615 SCV000608086 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-18 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Deficient protein function in appropriate functional assay(s);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759489 SCV000888834 likely pathogenic not provided 2018-05-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781001 SCV000918746 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.115T>A (p.Cys39Ser) results in a non-conservative amino acid change located in the Zinc finger, C3HC4 RING-type (IPR018957) domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 276852 control chromosomes (gnomAD). The variant, c.115T>A, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Judkins_2005, Beristain_2007, Sweet_2010, Blay_2013, Mgbemena_2017). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity (Starita_2015). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Multiple databases and publications classified variant as deleterious. Based on the evidence outlined above, the variant was classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111803 SCV000144348 uncertain significance Breast-ovarian cancer, familial 1 1998-03-04 no assertion criteria provided clinical testing

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