Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016569 | SCV001177534 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-18 | criteria provided, single submitter | clinical testing | The p.I946V variant (also known as c.2836A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 2836. The isoleucine at codon 946 is replaced by valine, 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. |
Invitae | RCV001236389 | SCV001409112 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-28 | 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: 821790). 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 isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 946 of the BRCA1 protein (p.Ile946Val). |
Center for Genomic Medicine, |
RCV002268405 | SCV002551011 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
University of Washington Department of Laboratory Medicine, |
RCV001016569 | SCV003849314 | 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). |