Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001304337 | SCV001493613 | uncertain significance | Familial cancer of breast | 2023-06-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 883 of the PALB2 protein (p.Lys883Glu). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PALB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1007192). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. |
| Ambry Genetics | RCV002451685 | SCV002739009 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-13 | criteria provided, single submitter | clinical testing | The p.K883E variant (also known as c.2647A>G), located in coding exon 7 of the PALB2 gene, results from an A to G substitution at nucleotide position 2647. The lysine at codon 883 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is 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. |
| Baylor Genetics | RCV001304337 | SCV004202174 | uncertain significance | Familial cancer of breast | 2023-07-11 | criteria provided, single submitter | clinical testing |