Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000637367 | SCV000758823 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-03-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 1080 of the BRCA1 protein (p.Leu1080Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 531225). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine 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 and their clinical significance is uncertain. 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, but this prediction has not been confirmed by published transcriptional studies. |
| University of Washington Department of Laboratory Medicine, |
RCV003157749 | SCV003850687 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Ambry Genetics | RCV003157749 | SCV004004382 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-12 | criteria provided, single submitter | clinical testing | The p.L1080V variant (also known as c.3238T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 3238. The leucine at codon 1080 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |