Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000476517 | SCV000550698 | uncertain significance | Familial cancer of breast | 2023-09-19 | 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. 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 not expected to disrupt PALB2 protein function. ClinVar contains an entry for this variant (Variation ID: 410158). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 797 of the PALB2 protein (p.Gln797Lys). |
| Ambry Genetics | RCV000567346 | SCV000663398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.Q797K variant (also known as c.2389C>A), located in coding exon 5 of the PALB2 gene, results from a C to A substitution at nucleotide position 2389. The glutamine at codon 797 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. |
| Color Diagnostics, |
RCV000567346 | SCV000910426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003318580 | SCV004022809 | uncertain significance | not provided | 2023-07-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24485656) |