Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214150 | SCV000278676 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-16 | criteria provided, single submitter | clinical testing | The p.V660I variant (also known as c.1978G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1978. The valine at codon 660 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is poorly 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, |
RCV000214150 | SCV000688358 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001040287 | SCV001203850 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 660 of the BRCA1 protein (p.Val660Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 34981296). ClinVar contains an entry for this variant (Variation ID: 234157). 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 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. |
University of Washington Department of Laboratory Medicine, |
RCV000214150 | SCV003849588 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
BRCAlab, |
RCV003493534 | SCV004244106 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |