Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566115 | SCV000664786 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-03 | criteria provided, single submitter | clinical testing | The p.H236R variant (also known as c.707A>G), located in coding exon 8 of the BRCA2 gene, results from an A to G substitution at nucleotide position 707. The histidine at codon 236 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not 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, |
RCV000566115 | SCV000906501 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001369134 | SCV001565564 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 236 of the BRCA2 protein (p.His236Arg). This variant is present in population databases (rs80358938, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 52263). 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 with a negative predictive value of 95%. 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. |
| Myriad Genetics, |
RCV000114055 | SCV004018644 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-06-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
| Baylor Genetics | RCV003460606 | SCV004216062 | uncertain significance | Familial cancer of breast | 2023-06-28 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000114055 | SCV000147551 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2003-12-23 | no assertion criteria provided | clinical testing |