Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000693232 | SCV000821092 | uncertain significance | Familial cancer of breast | 2024-01-13 | 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 384 of the PALB2 protein (p.Glu384Lys). This variant is not present in population databases (gnomAD no frequency). 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: 571957). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PALB2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Color Diagnostics, |
RCV001181141 | SCV001346230 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001181141 | SCV002621546 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.E384K variant (also known as c.1150G>A), located in coding exon 4 of the PALB2 gene, results from a G to A substitution at nucleotide position 1150. The glutamic acid at codon 384 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in at least one breast cancer patient in a study of 13087 breast cancer cases and 5488 control individuals in the UK (Decker B et al. J Med Genet, 2017 11;54:732-741). 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. |
| Fulgent Genetics, |
RCV002493183 | SCV002778029 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 | 2021-09-29 | criteria provided, single submitter | clinical testing |