Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001776421 | SCV002012966 | uncertain significance | not provided | 2020-07-21 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); 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 |
| Labcorp Genetics |
RCV002034510 | SCV002311869 | uncertain significance | Familial cancer of breast | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 915 of the PALB2 protein (p.Ala915Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1320442). 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 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. |
| Ambry Genetics | RCV002440870 | SCV002748940 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | The p.A915V variant (also known as c.2744C>T), located in coding exon 7 of the PALB2 gene, results from a C to T substitution at nucleotide position 2744. The alanine at codon 915 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Baylor Genetics | RCV002034510 | SCV004202679 | uncertain significance | Familial cancer of breast | 2023-01-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526147 | SCV005039927 | uncertain significance | not specified | 2024-03-09 | criteria provided, single submitter | clinical testing |