Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220349 | SCV000278655 | likely benign | Hereditary cancer-predisposing syndrome | 2024-08-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Gene |
RCV000235363 | SCV000293968 | uncertain significance | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26822949, 28481359) |
| Labcorp Genetics |
RCV000466160 | SCV000550648 | uncertain significance | Familial cancer of breast | 2024-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 358 of the PALB2 protein (p.Pro358Ser). 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: 234140). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PALB2 protein function with a negative predictive value of 80%. 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, |
RCV000220349 | SCV000690762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-17 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 358 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002494599 | SCV002786154 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 | 2021-09-23 | criteria provided, single submitter | clinical testing |