Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000467390 | SCV000549370 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 52 of the BRCA1 protein (p.Leu52Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 409340). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 30209399). 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. |
| Ambry Genetics | RCV000574272 | SCV000660958 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-01 | criteria provided, single submitter | clinical testing | The p.L52P variant (also known as c.155T>C), located in coding exon 3 of the BRCA1 gene, results from a T to C substitution at nucleotide position 155. The leucine at codon 52 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. One study found that this nucleotide substitution has intermediate functionality in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477971 | SCV004222569 | uncertain significance | not provided | 2023-02-10 | criteria provided, single submitter | clinical testing | The variant has not been reported in individuals with BRCA1-related cancers in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). One study showed this variant apparently retained intermediate functional activity in a large-scale study using a haploid cell line (PMID: 30209399 (2018)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Brotman Baty Institute, |
RCV001075937 | SCV001241596 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |