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 | 2021-11-22 | 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, 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 | RCV001212287 | SCV001383867 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-08-17 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 823906). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 1181 of the BRCA1 protein (p.Val1181Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. |
| 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 |