Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020561 | SCV001182057 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-01 | criteria provided, single submitter | clinical testing | The p.V1181F variant (also known as c.3541G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3541. The valine at codon 1181 is replaced by phenylalanine, an amino acid with highly similar properties. This variant has been identified in 1/12502 unselected Japanese colorectal cancer patients and in 3/23702 controls (Fujita M et al. Clin Gastroenterol Hepatol, 2020 Dec). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001212287 | SCV001383867 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1181 of the BRCA1 protein (p.Val1181Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 823906). 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, |
RCV001020561 | SCV003850315 | 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230620 | SCV003928342 | uncertain significance | not specified | 2023-04-23 | criteria provided, single submitter | clinical testing |