Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000553689 | SCV000633266 | uncertain significance | Familial cancer of breast | 2023-04-08 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt PALB2 protein function. ClinVar contains an entry for this variant (Variation ID: 460885). This missense change has been observed in individual(s) with breast cancer (PMID: 28825143, 30287823). This variant is present in population databases (rs769097541, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 398 of the PALB2 protein (p.Val398Met). |
Color Diagnostics, |
RCV000771520 | SCV000904034 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000771520 | SCV001170323 | likely benign | Hereditary cancer-predisposing syndrome | 2018-04-23 | 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. |
Leiden Open Variation Database | RCV001030202 | SCV001193070 | uncertain significance | not provided | 2018-10-10 | no assertion criteria provided | curation | Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. |