Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001063006 | SCV001227835 | uncertain significance | Familial cancer of breast | 2021-08-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 PALB2-related conditions. This sequence change replaces cysteine with tyrosine at codon 520 of the PALB2 protein (p.Cys520Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Ambry Genetics | RCV002402443 | SCV002704406 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-27 | criteria provided, single submitter | clinical testing | The p.C520Y variant (also known as c.1559G>A), located in coding exon 4 of the PALB2 gene, results from a G to A substitution at nucleotide position 1559. The cysteine at codon 520 is replaced by tyrosine, an amino acid with highly 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. |