Total submissions: 4
| 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, |
RCV001073073 | SCV001238565 | not provided | Breast-ovarian cancer, familial 1 | no assertion provided | in vitro |