Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040558 | SCV001204139 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-10-13 | 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, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with asparagine at codon 1625 of the BRCA1 protein (p.Tyr1625Asn). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and asparagine. |
| Ambry Genetics | RCV002339200 | SCV002635593 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-23 | criteria provided, single submitter | clinical testing | The p.Y1625N variant (also known as c.4873T>A), located in coding exon 14 of the BRCA1 gene, results from a T to A substitution at nucleotide position 4873. The tyrosine at codon 1625 is replaced by asparagine, an amino acid with dissimilar 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. |