Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Human Genetics Unit, |
RCV000993768 | SCV000928312 | likely pathogenic | Familial cancer of breast | 2019-07-24 | criteria provided, single submitter | clinical testing | This c.2768T>G (Val923Gly) variant in PALB2 has been seen in a patient having breast cancer with a family history of breast and thyroid cancer. This mutation is not found in global population frequency databases or in our internal exome database. In silico analysis concluded this variant as disease-causing. According to ACMG criteria (2015), this variant can be classified as Likely pathogenic (II). Evidence: PS4, PM2, PP2, PP3, PP4, BP1 |
Labcorp Genetics |
RCV000993768 | SCV002179154 | uncertain significance | Familial cancer of breast | 2023-06-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 638155). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 923 of the PALB2 protein (p.Val923Gly). |