Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011756 | SCV001172115 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-18 | criteria provided, single submitter | clinical testing | The p.L49R variant (also known as c.146T>G and 265T>G), located in coding exon 3 of the BRCA1 gene, results from a T to G substitution at nucleotide position 146. The leucine at codon 49 is replaced by arginine, an amino acid with dissimilar 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. |
| Color Diagnostics, |
RCV001011756 | SCV001351371 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001301250 | SCV001490414 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 49 of the BRCA1 protein (p.Leu49Arg). This variant is present in population databases (rs273897660, gnomAD 0.0009%). 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: 54263). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. Experimental studies have shown that this missense change does not substantially affect 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. |
| Breast Cancer Information Core |
RCV000111885 | SCV000144469 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | ||
| Brotman Baty Institute, |
RCV000111885 | SCV001242466 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |