Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000800217 | SCV000939917 | uncertain significance | Familial cancer of breast | 2018-09-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 895 of the PALB2 protein (p.Val895Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant has not been reported in the literature in individuals with PALB2-related disease. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002458455 | SCV002739083 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | The p.V895F variant (also known as c.2683G>T), located in coding exon 7 of the PALB2 gene, results from a G to T substitution at nucleotide position 2683. The valine at codon 895 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |