ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.271T>C (p.Cys91Arg) (rs786203939)

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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 RCV000167457 SCV000218313 uncertain significance Hereditary cancer-predisposing syndrome 2014-12-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000559106 SCV000635862 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-03-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 91 of the BRCA1 protein (p.Cys91Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 187707). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000780975 SCV000918686 uncertain significance not specified 2018-03-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.271T>C (p.Cys91Arg) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 121322 control chromosomes (ExAC). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.271T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Brotman Baty Institute,University of Washington RCV001073073 SCV001238565 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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