Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000548954 | SCV000633383 | uncertain significance | Familial cancer of breast | 2022-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 956 of the PALB2 protein (p.Glu956Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 460963). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV001016830 | SCV001177828 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-28 | criteria provided, single submitter | clinical testing | The p.E956K variant (also known as c.2866G>A), located in coding exon 9 of the PALB2 gene, results from a G to A substitution at nucleotide position 2866. The glutamic acid at codon 956 is replaced by lysine, an amino acid with 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478138 | SCV004222320 | uncertain significance | not provided | 2023-05-03 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00014 (5/34580 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Institute for Biomarker Research, |
RCV001016830 | SCV004228038 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003493628 | SCV004242683 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |