Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002335979 | SCV002642462 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-19 | criteria provided, single submitter | clinical testing | The p.F170S variant (also known as c.509T>C), located in coding exon 5 of the BRCA2 gene, results from a T to C substitution at nucleotide position 509. The phenylalanine at codon 170 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003096612 | SCV003243334 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-06-01 | 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. 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 BRCA2 protein function. This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 170 of the BRCA2 protein (p.Phe170Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. |