Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000472157 | SCV000547259 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2016-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 361 of the BRIP1 protein (p.Asp361Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRIP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV004022667 | SCV005029037 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | The p.D361Y variant (also known as c.1081G>T), located in coding exon 7 of the BRIP1 gene, results from a G to T substitution at nucleotide position 1081. The aspartic acid at codon 361 is replaced by tyrosine, an amino acid with highly dissimilar 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. |