Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001231551 | SCV001404078 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2020-09-20 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 131 of the BRIP1 protein (p.Lys131Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002375233 | SCV002625155 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | The p.K131N variant (also known as c.393A>C), located in coding exon 4 of the BRIP1 gene, results from an A to C substitution at nucleotide position 393. The lysine at codon 131 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |