Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001052786 | SCV001217012 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with phenylalanine at codon 14 of the BRCA1 protein (p.Val14Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). 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. |
| Brotman Baty Institute, |
RCV001078128 | SCV001244176 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |