Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571563 | SCV000661107 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-05-21 | criteria provided, single submitter | clinical testing | The p.L1854P variant (also known as c.5561T>C), located in coding exon 22 of the BRCA1 gene, results from a T to C substitution at nucleotide position 5561. The leucine at codon 1854 is replaced by proline, an amino acid with similar properties. Protein functional assays have demonstrated that this alteration is non-functional (Findlay GM et al. Nature, 2018 10;562:217-222; Fernandes VC et al. J Biol Chem, 2019 04;294:5980-5992; Lee MS et al. Cancer Res., 2010 Jun;70:4880-90; Adamovich AI et al. Am J Hum Genet 2022 Apr;109(4):618-630). This alteration was also detected in 1/1664 individuals diagnosed with breast and/or ovarian cancer (Zhang Y et al. BMC Cancer, 2022 Aug;22:842).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV001326885 | SCV001517938 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-12-17 | 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 20516115, 30209399). 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. ClinVar contains an entry for this variant (Variation ID: 55631). 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 leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1854 of the BRCA1 protein (p.Leu1854Pro). |
| Center for Genomic Medicine, |
RCV003493430 | SCV004242791 | likely pathogenic | not provided | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003493430 | SCV005081126 | likely pathogenic | not provided | 2023-12-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5680T>C; This variant is associated with the following publications: (PMID: 30765603, 35196514, 29884841, 32377563, 35918668, 20516115, 28781887, 30209399, 35665744, 25348405, 31131967) |
| Sharing Clinical Reports Project |
RCV000083223 | SCV000115297 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-02-07 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000083223 | SCV000145579 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2003-12-23 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000083223 | SCV001242158 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro | ||
| Center for Precision Medicine, |
RCV002250547 | SCV002520768 | uncertain significance | Familial cancer of breast | no assertion criteria provided | literature only |