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 | The p.C91R variant (also known as c.271T>C and 390T>C), located in coding exon 4 of the BRCA1 gene, results from a T to C substitution at nucleotide position 271. The cysteine at codon 91 is replaced by arginine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,502 samples (13,004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 105,000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.C91R remains unclear. |
| Labcorp Genetics |
RCV000559106 | SCV000635862 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-12-26 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 187707). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 91 of the BRCA1 protein (p.Cys91Arg). |
| Women's Health and 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, susceptibility to, 1 | no assertion provided | in vitro |