Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001204321 | SCV001375522 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-09-03 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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). This sequence change replaces serine with asparagine at codon 226 of the BRIP1 protein (p.Ser226Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. |
Ambry Genetics | RCV003163544 | SCV003859882 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-09 | criteria provided, single submitter | clinical testing | The p.S226N variant (also known as c.677G>A), located in coding exon 6 of the BRIP1 gene, results from a G to A substitution at nucleotide position 677. The serine at codon 226 is replaced by asparagine, 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. |