Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000226853 | SCV000289795 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 240800). 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 histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1402 of the BRCA1 protein (p.His1402Pro). |
Sema4, |
RCV002257592 | SCV002538275 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-27 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002257592 | SCV002627312 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-21 | criteria provided, single submitter | clinical testing | The p.H1402P variant (also known as c.4205A>C), located in coding exon 11 of the BRCA1 gene, results from an A to C substitution at nucleotide position 4205. The histidine at codon 1402 is replaced by proline, an amino acid with similar 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. |