Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805297 | SCV000945248 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-08-19 | 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 650198). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1398 of the BRCA1 protein (p.Asp1398Asn). |
| Ambry Genetics | RCV002332644 | SCV002627067 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-15 | criteria provided, single submitter | clinical testing | The p.D1398N variant (also known as c.4192G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4192. The aspartic acid at codon 1398 is replaced by asparagine, 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. |