Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000706354 | SCV000835398 | uncertain significance | Familial cancer of breast | 2022-02-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PALB2-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 582313). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1081 of the PALB2 protein (p.Glu1081Gly). |
| Ambry Genetics | RCV002442535 | SCV002611797 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-20 | criteria provided, single submitter | clinical testing | The p.E1081G variant (also known as c.3242A>G), located in coding exon 12 of the PALB2 gene, results from an A to G substitution at nucleotide position 3242. The glutamic acid at codon 1081 is replaced by glycine, 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. |