Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000635623 | SCV000757043 | uncertain significance | Familial cancer of breast | 2022-12-02 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.002%). 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 expected to disrupt PALB2 protein function. ClinVar contains an entry for this variant (Variation ID: 530038). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 707 of the PALB2 protein (p.Pro707Leu). |
| Ambry Genetics | RCV001014519 | SCV001175234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-17 | criteria provided, single submitter | clinical testing | The p.P707L variant (also known as c.2120C>T), located in coding exon 5 of the PALB2 gene, results from a C to T substitution at nucleotide position 2120. The proline at codon 707 is replaced by leucine, an amino acid with similar properties. This alteration was found to be functionally normal in multiple assays including homology-directed DNA repair (HDR), sensitivity to PARP inhibitor and cisplatin sensitivity (Boonen RACM et al. Nat Commun, 2019 11;10:5296). This amino acid position is highly 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. |
| Baylor Genetics | RCV000635623 | SCV004202606 | uncertain significance | Familial cancer of breast | 2023-06-09 | criteria provided, single submitter | clinical testing |